Publications by authors named "Jixi Zhang"

45 Publications

Intervention of Polydopamine Assembly and Adhesion on Nanoscale Interfaces: State-of-the-Art Designs and Biomedical Applications.

Adv Healthc Mater 2021 Mar 9:e2002138. Epub 2021 Mar 9.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044, China.

The translation of mussel-inspired wet adhesion to biomedical engineering fields have catalyzed the emergence of polydopamine (PDA)-based nanomaterials with privileged features and properties of conducting multiple interfacial interactions. Recent concerns and progress on the understanding of PDA's hierarchical structure and progressive assembly are inspiring approaches toward novel nanostructures with property and function advantages over simple nanoparticle architectures. Major breakthroughs in this field demonstrated the essential role of π-π stacking and π-cation interactions in the rational intervention of PDA self-assembly. In this review, the recently emerging concepts in the preparation and application of PDA nanomaterials, including 3D mesostructures, low-dimensional nanostructures, micelle/nanoemulsion based nanoclusters, as well as other multicomponent nanohybrids by the segregation and organization of PDA building blocks on nanoscale interfaces are outlined. The contribution of π-electron interactions on the interfacial loading/release of π electron-rich molecules (nucleic acids, drugs, photosensitizers) and the exogenous coupling of optical energy, as well as the impact of wet-adhesion interactions on the nano-bio interface interplay, are highlighted by discussing the structure-property relationships in their featured applications including fluorescent biosensing, gene therapy, drug delivery, phototherapy, combined therapy, etc. The limitations of current explorations, and future research directions are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202002138DOI Listing
March 2021

Engineering of a Core-Shell Nanoplatform to Overcome Multidrug Resistance via ATP Deprivation.

Adv Healthc Mater 2020 10 18;9(20):e2000432. Epub 2020 Sep 18.

Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.

Inhibiting the function of P-glycoprotein (P-gp) transporter, which causes drug efflux through adenosine triphosphate (ATP)-dependent manner, has become an effective strategy to conquer multidrug resistance (MDR) of cancer cells. However, there remains challenges for effective co-delivery, sequential release of P-gp modulator and chemotherapeutic agent. In this work, a novel type of core-shell nanoparticle is reported. It can independently encapsulate a high amount (about 683 µg mg ) of chemotherapeutic agent doxorubicin (DOX) in the mesoporous polydopamine (MPDA) core and glucose oxidase (GOx) in the zeolite imidazolate frameworks-8 (ZIF-8) shell, namely MPDA@ZIF-8/DOX+GOx. The fast release of GOx triggered by acid-sensitive degradation of the ZIF-8 shell consumes glucose to starve cancer cells for ATP deprivation and effective suppress ATP-dependent drug efflux in advance, and then effectively facilitates the accumulation of DOX in MCF-7/ADR cancer cells. Experiments in vitro and in vivo demonstrate that the fabricated nanosystem can dramatically improve anticancer effects for MDR through sequential release property and exhibit excellent biocompatibility. Overall, this work reveals new insights in the use of GOx for MDR treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202000432DOI Listing
October 2020

Near-Infrared Light-Triggered Nitric-Oxide-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy for Biofilm Elimination.

ACS Nano 2020 03 24;14(3):3546-3562. Epub 2020 Feb 24.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.

Photothermal treatment (PTT) involving a combination of therapeutic modalities recently emerged as an efficient alternative for combating biofilm. However, PTT-related local high temperature may destroy the surrounding healthy tissues. Herein, we present an all-in-one phototherapeutic nanoplatform consisting of l-arginine (l-Arg), indocyanine green (ICG), and mesoporous polydopamine (MPDA), namely, AI-MPDA, to eliminate the already-formed biofilm. The fabrication process included surface modification of MPDA with l-Arg and further adsorption of ICG π-π stacking. Under near-infrared (NIR) exposure, AI-MPDA not only generated heat but also produced reactive oxygen species, causing a cascade catalysis of l-Arg to release nitric oxide (NO). Under NIR irradiation, biofilm elimination was attributed to the NO-enhanced photodynamic therapy and low-temperature PTT (≤45 °C). Notably, the NIR-triggered all-in-one strategy resulted in severe destruction of bacterial membranes. The phototherapeutic AI-MPDA also displayed good cytocompatibility. NIR-irradiated AI-MPDA nanoparticles not only prevented bacterial colonization but also realized a rapid recovery of infected wounds. More importantly, the all-in-one phototherapeutic platform displayed effective biofilm elimination with an efficiency of around 100% in a abscess formation model. Overall, this low-temperature phototherapeutic platform provides a reliable tool for combating already-formed biofilms in clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b09871DOI Listing
March 2020

Ionic liquid-induced nanoporous structures of polymer films.

Chem Commun (Camb) 2020 Mar;56(20):3054-3057

College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, China.

We present a new strategy for the fabrication of nanoporous polymer films assembled using strong polyelectrolyte pairs in ionic liquid aqueous solutions. These nanoporous films show good anti-reflection properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc08768kDOI Listing
March 2020

Hybrid mesoporous nanorods with deeply grooved lateral faces toward cytosolic drug delivery.

Biomater Sci 2019 Dec 16;7(12):5301-5311. Epub 2019 Oct 16.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, Turku 20520, Finland.

Nanocarriers with high local curvatures hold a great potential of inducing effective penetration of intracellular barriers and cytosolic delivery of membrane-impermeable drugs. However, the fine control of the sharp edges and their morphological effects inside cells remains largely unexplored. Herein, a nanocarrier system of hybrid mesoporous nanorods with six-arm star-shaped end faces and groove-patterned lateral faces was developed to maximize surface regions with high local curvatures for enhancing membrane destabilization. Specifically, twisted (right-handed) nanorods (TNR, diameter ∼120, aspect ratio 4-5) with a hexagon cross-section from a templated synthesis were modified by amino groups to promote surface coating of a wet-adhesive polymer, i.e. polydopamine (PDA). An edge-preferential deposition of PDA by local curvature effects led to the protective etching of silica, and in turn, the formation of nanorods with varying groove depths at different volumes of the aqueous coating solution. Finally, branched polyethylene imine (PEI) was grafted on the exterior surface of the nanorods for enhancing the dispersity and cellular uptake rate. As verified by elaborate in vitro investigations, the configuration of nanorods with the sharpest edges/deepest grooves can be rotated to a lying-down/upright mode in order to minimize/maximize the membrane tension during the interaction with membranes, which consequently resulted in highly efficient lysosomal escape despite the relatively lower uptake degree. The successful delivery of vorinostat (SAHA, a FDA-approved histone deacetylase inhibitor) and inhibition of cancer cells demonstrated the attractive ability of the nanocarriers in drug delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9bm01251fDOI Listing
December 2019

Remote eradication of biofilm on titanium implant via near-infrared light triggered photothermal/photodynamic therapy strategy.

Biomaterials 2019 12 6;223:119479. Epub 2019 Sep 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, China; Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, China. Electronic address:

Biofilm formation is a main challenge in treatment of bone-implant-associated infections, resulting in tolerance to immune system and antibiotics. However, smart non-surgical or non-invasive treatment methods of combating established biofilm on an implant have been less reported. Herein, a therapeutic system consisting of mesoporous polydopamine nanoparticles (MPDA) to combat biofilm is reported for the first time. We develop a synergistic photothermal/photodynamic therapy (PTT/PDT) strategy aiming for biofilms eradication on titanium (Ti) implant, which is integrated with MPDA loading with photosensitizer Indocyanine Green (ICG) by π-π stacking. Specifically, MPDA is functionalized with RGD peptide to endow the modified Ti sample (Ti-M/I/RGD) with good cytocompatibility. More importantly, Ti-M/I/RGD implant remarkably kills Staphylococcus aureus (S. aureus) biofilm with an efficiency of 95.4% in vivo upon near infrared (NIR). After biofilm eradication, implant still displays great performance regarding osteogenesis and osseointegration. Overall, this study provides a PTT/PDT strtategy for the development of antibacterial Ti implants for potential orthpediac application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2019.119479DOI Listing
December 2019

Interface-Hybridization-Enhanced Photothermal Performance of Polypyrrole/Polydopamine Heterojunctions on Porous Nanoparticles.

Macromol Rapid Commun 2019 Oct 28;40(19):e1900263. Epub 2019 Jul 28.

Key Laboratory of Biorheological Science and Technology, Ministry of EducationCollege of BioengineeringChongqing University, No. 174 Shazheng Road, Chongqing, 400044, China.

Photothermal conversion agents (PTCAs) based on π-conjugated polymers are promising for cancer therapy, but the alteration of bandgap energies toward boosted photothermal properties remains challenging. Herein, polymer PTCAs with heterojunctions of a binary optical component are developed by interface hybridization on porous particles. Specifically, polypyrrole (PPy) nanodomains are successfully hosted on the wet-adhesive surface of mesoporous polydopamine nanoparticles through the loading and polymerization of pyrrole in the confined pore space (≈5.0 nm). The near-infrared absorbing polymers in the heterojunctions possess similar five-membered heterocyclic rings and can interact mutually to generate photoinduced electron transfer (PET). Such a large-area optoelectronic interaction progressively reduces the bandgap energy (down to 0.56 eV) by increasing the doped amount of PPy, which consequently enhances the extinction coefficient and photothermal conversion efficiency by 4.6- and 2.2-fold, respectively. Notably, the hybrid PTCA exhibits good biocompatibility, photocytotoxicity, and great potential for cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/marc.201900263DOI Listing
October 2019

Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs.

Int J Mol Sci 2019 Jul 11;20(14). Epub 2019 Jul 11.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity (3rd floor), Tykistökatu 6A, FI 20520 Turku, Finland.

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive "molecular-glue" function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20143408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679059PMC
July 2019

Hexagonal polypyrrole nanosheets from interface driven heterogeneous hybridization and self-assembly for photothermal cancer treatment.

Chem Commun (Camb) 2019 Apr;55(30):4359-4362

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Hexagonal polypyrrole (PPy) nanosheets with highly ordered lateral orientation were developed by the generation and directed self-assembly of dopamine induced FeOOH-PPy heterostructures on nanoscale THF/water interfaces. The size-controlled nanosheets possess attractive photothermal conversion properties, which facilitate efficient photothermal inhibition of cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc00809hDOI Listing
April 2019

Temporally Controlled Photothermal/Photodynamic and Combined Therapy for Overcoming Multidrug Resistance of Cancer by Polydopamine Nanoclustered Micelles.

ACS Appl Mater Interfaces 2019 Apr 2;11(15):13945-13953. Epub 2019 Apr 2.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering , Chongqing University , No. 174 Shazheng Road , Chongqing 400044 , China.

Currently, the simple integration of multiple therapeutic agents within a single nanostructure for combating multidrug resistance (MDR) tumors yet remains a challenge. Herein, we report a photoresponsive nanocluster (NC) system prepared by installing polydopamine (PDA) nanoparticle clusters on the surface of d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) (a drug efflux inhibitor) micelles solubilized with IR780 (a photosensitizer) to achieve a combined chemotherapy (CT)/photothermal therapy (PTT)/photodynamic therapy (PDT) for drug-resistant breast cancer. Mediated by the fluorescence resonance energy transfer and radical scavenging properties of PDA, NC shows prominently quenched fluorescence emission (∼78%) and inhibited singlet oxygen generation (∼67%) upon exposure to near-infrared (NIR) light (808 nm, 0.5 W cm), favoring a highly efficient PTT module. Meanwhile, the photothermal heat can also boost the release of doxorubicin hydrochloride whose intracellular accumulation can be greatly enhanced by TPGS. Interestingly, the first NIR irradiation and subsequent incubation (∼24 h) can induce the gradual relocation and disintegration of PDA nanoparticles, thereby leading to activated PDT therapy under the second irradiation. Upon the temporally controlled sequential application of PTT/PDT, the developed NC exhibited a great potential to treat MDR cancer both in vitro and in vivo. These findings suggest that complementary interactions among PTT/PDT/CT modalities can enhance the efficiency of the combined therapy for MDR tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b00472DOI Listing
April 2019

CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy.

Acta Biomater 2019 03 3;86:416-428. Epub 2019 Jan 3.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Combined photothermal and gene therapy provides a promising modality toward cancer treatment, yet facile integration and controlled codelivery of gene payloads and photothermal conversion agents (PTCAs) remains a great challenge. Inspired by the robust wet adhesion of marine mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%). Moreover, a successful calcium phosphate (CaP) coating via biomineralization was constructed on the cationic nanoparticle to prohibit premature release of siRNA. The CaP coating underwent biodegradation in weakly-acidic subcellular conditions (lysosomes). The synergistic integration of tertiary amines and catechol moieties on the subsequently exposed surfaces was demonstrated to feature the destabilization/disruption ability toward model cellular membranes via the greatly enhanced interfacial adhesion and interactions. Consequently, sufficient permeability of lysosomal membranes, and in turn, a high lysosomal escape efficiency, was realized, which then resulted in high gene silencing efficiencies via sufficient cytosolic delivery of siRNA. When an efficient knocking down (65%) of survivin (an inhibitor of apoptosis proteins) was combined with a subsequent photothermal ablation, remarkably higher therapeutic efficiencies were observed both in vitro and in vivo, as compared with monotherapy. The system may help to pave a new avenue on the utilization of bio-adhesive surfaces for handling the obstacles of combined photothermal and gene therapy. STATEMENT OF SIGNIFICANCE: Polydopamine (PDA) based porous photothermal-conversion agent (PTCA) with sufficiently high conversion efficiency was employed to deliver photothermal/gene therapy modalities towards cancer treatment. CaP coating via PDA-induced biomineralization was constructed to prohibit premature release of siRNA loaded in the pore space of the nanocarriers. Responsive degradation of CaP also led to the exposure of membrane-lytic surfaces built through the synergistic integration of tertiary amines and catechol moieties, and in turn the significantly enhanced lysosomal escape and cytosol siRNA delivery. Therapeutic targeting of survivin was successfully applied for activation of apoptosis and programmed cell death. Combined photothermal and gene therapy improved therapeutic effectiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2019.01.002DOI Listing
March 2019

Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures.

Pharmaceutics 2018 Nov 17;10(4). Epub 2018 Nov 17.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20521 Turku, Finland.

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics10040237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320991PMC
November 2018

Hierarchically stimuli-responsive nanovectors for improved tumor penetration and programed tumor therapy.

Nanoscale 2018 Jul;10(28):13737-13750

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Poor drug delivery to solid tumors remains a great challenge for effective antitumor therapy. Herein, multistage stimuli-responsive nanovectors based on hollow mesoporous silica nanoparticles (HMSNs) were prepared to avoid delivery barriers for improved penetration and programmed tumor therapy. The versatile nanosystem was constructed through electrostatic complexation between the functional HMSNs loaded with gemcitabine (GEM) and the small-sized platinum prodrug-conjugated poly(amidoamine) dendrimer (PAMAM-Pt). The HMSNs were functionalized with dimethylmaleic anhydride tethered chitosan oligosaccharide to endow the particles of HMSN-CS(DMA) with charge-reversal properties. The as-prepared nanosystem had a stable structure of size ∼130 nm at pH 7.4, which is beneficial for blood circulation and tumor vessel extravasation of nanocarriers. Once it reaches the tumor site, the nanosystem can dissociate into HMSN@GEM-CS (∼120 nm) and PAMAM-Pt dendrimer nanocarriers (∼5 nm) in response to the acidic tumor microenvironment because of the acid-mediated charge-reversal, then the HMSN@GEM can play the antitumor role in surface tumor tissues. The dissociated PAMAM-Pt showed excellent performance in tumor penetration, cell uptake and intracellular trafficking due to the small size and positive charge, which was supported by the study of three-dimensional multicellular spheroids in vitro. Finally, the active cisplatin was released from the PAMAM-Pt dendrimer under the intracellular reducing environment to kill cells in deep tumor tissues. The significant tumor suppression of this system in vivo was validated in the A549 tumor xenografted mouse model. Such a stimuli-responsive nanosystem that integrates simple preparation, biocompatibility, biodegradability and programmed tumor therapy manifests great potential for clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8nr02971gDOI Listing
July 2018

Stable photoluminescence of lanthanide complexes in aqueous media through Metal-Organic Frameworks Nanoparticles with plugged surface.

J Colloid Interface Sci 2018 Oct 17;527:68-77. Epub 2018 May 17.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China. Electronic address:

The photoluminescence stability of lanthanide complex in aqueous media is a prerequisite for diagnostics probes. The combination of building blocks working in concert to facilitate host-guest structures is now considered state of the art in surpassing this roadblock, yet there still remains a tremendous challenge. Here, a stable, highly-luminescent system was developed through trapping anionic complexes sensitized by tridentate pyridine-tetrazolate (pytz) ligands within the rigid framework of ZIF-8 (zeolitic imidazolate framework-8) particles (∼60 nm in size). The key to maintaining the stable luminescence of lanthanide complexes inside ZIF-8 frameworks is a stopcock design, i.e. stopper molecules (an imidazolium based ionic liquid) selectively plugged on the pore entrances located at the exterior surface of the ZIF-8 host, which protect both the host and the guests from deteriorations by surrounding ions/water molecules. Remarkably, the obtained Ln complex encapsulated ZIF-8 particles (Ln = terbium, europium) particles possessed high quantum yields (23.2% and 8.5%), large absorption cross-section (∼10 cm), and long luminescence lifetimes (1.9 and 3.0 ms) in PBS buffer. In addition, the system can realize single/multi-color encoding by altering the loading amounts and the weight ratios of complexes emitting at different wavelengths.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2018.05.025DOI Listing
October 2018

Hybrid Mesoporous-Microporous Nanocarriers for Overcoming Multidrug Resistance by Sequential Drug Delivery.

Mol Pharm 2018 07 24;15(7):2503-2512. Epub 2018 May 24.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering , Chongqing University , No. 174 Shazheng Road , Chongqing 400044 , China.

Combination chemotherapy with a modulator and a chemotherapeutic drug has become one of the most promising strategies for the treatment of multidrug resistance (MDR) in cancer therapy. However, the development of nanocarriers with a high payload and sequential release of therapeutic agents poses a significant challenge. In this work, we report a type of hybrid nanocarriers prepared by polydopamine (PDA) mediated integration of the mesoporous MSN core and the microporous zeolite imidazolate frameworks-8 (ZIF-8) shell. The nanocarriers exploit storage capacities for drugs based on the high porosity and molecular sieving capabilities of ZIF-8 for sequential drug release. Particularly, large amounts of an anticancer drug (DOX, 607 μg mg) and a MDR inhibitor curcumin (CUR, 778 μg mg) were sequentially loaded in the mesoporous core via π-π stacking interactions mediated by PDA and in the microporous shell via the encapsulation during ZIF-8 growth. The sustained release of DOX was observed to follow earlier and faster release of CUR by acid-sensitive dissolution of the ZIF-8 shell. Furthermore, the nanoparticles showed good biocompatibility and effective cellular uptake in in vitro evaluations using drug-resistant MCF-7/ADR cancer cells. More importantly, the preferentially released CUR inhibited the drug efflux function of the membrane P-glycoprotein (P-gp), which subsequently facilitated the nuclear transportation of DOX released from the PDA-MSN core, and, in turn, the synergistic effects on killing MDR cancer cells. The hybrid mesoporous-microporous nanocarrier holds great promise for combination chemotherapy applications on the basis of sequential drug release.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.7b01096DOI Listing
July 2018

Interfacially active polydopamine for nanoparticle stabilized nanocapsules in a one-pot assembly strategy toward efficient drug delivery.

J Mater Chem B 2018 Mar 6;6(12):1754-1763. Epub 2018 Mar 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Nanoscale colloidal capsules are promising drug delivery carriers currently while the demand for multiple-step syntheses and the difficulties in achieving high capsule stability are key obstacles that have greatly restricted their development. Herein, we report a polydopamine (PDA) nanoparticle stabilized nanocapsule as a drug delivery system based on the combination of nanoparticle formation and capsule assembly/stabilization in one pot. In this system, an arginine modified linoleic acid nanoemulsion was employed as the template for the in situ generation/assembly of interfacially active PDA nanoparticles, while directional interaction pairs of carboxylate-guanidine and amino-PDA linked by arginine are involved in the assembly process. The nanocapsules possess an average size of 100 nm, high stability in biological media, and efficient lipophilic transfer of the loaded lipophilic cargo. Notably, the high biocompatibility of the nanocapsules and the non-endocytotic delivery to the cytosol of cancer cells were demonstrated in vitro. Furthermore, the efficient delivery of paclitaxel, as well as paclitaxel/doxorubicin dual cargo, was realized, resulting in the high inhibition of cancer cells. Altogether, the PDA nanoparticle stabilized nanocapsules open new opportunities for the development of promising nanocapsule platforms for biomedical delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7tb03008hDOI Listing
March 2018

Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy.

Biomaterials 2018 03 9;157:107-124. Epub 2017 Dec 9.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China; Chongqing Collaborative Innovation Center for Minimally-invasive and Noninvasive Medicine, Chongqing 400016, PR China. Electronic address:

The study reports a multifunctional nanoplatform based on mesoporous silica coated gold nanorod (AuNR@MSN) to overcome biological barriers associating with nanocarrier for multiple enhanced photodynamic therapy (PDT) and photothermal therapy (PPT). Indocyanine green (ICG) was loaded into AuNR@MSN and end-capped with β-cyclodextrin (β-CD). Then, a peptide RLA ([RLARLAR]) with plasma membrane permeability and mitochondria-targeting capacity was anchored to AuNR@MSN via host-gust interaction. Subsequently, a charge-reversible polymer was introduced to endow stealth property. When the nanoplatform extravasates to tumor tissue, the weak acidity in tumor microenvironment could induce the dissociation of charge-reversible polymer and re-exposure of RLA peptide. Such a pH-mediated transition could facilitate the targeted accumulation of the nanoplatform in mitochondria. Upon singular 808 nm laser irradiation, the nanoplatform displayed enhanced PDT effect through the generation of reactive oxygen species (ROS) mediated by the local electric field of AuNR, plasmonic photothermal effect, and leakage of endogenous ROS by mitochondrion-targeted PDT. Meanwhile, local hyperthermia was generated by both ICG and AuNR for PPT. The in vitro and in vivo experiments demonstrated that the composite nanoplatform had good antitumor effect with minimal side effect. This work provides new insight into the development of new phototherapeutics for oncotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2017.12.003DOI Listing
March 2018

Integration of polymers in the pore space of mesoporous nanocarriers for drug delivery.

J Mater Chem B 2017 Dec 6;5(45):8891-8903. Epub 2017 Nov 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

In the past decade, controlled integration of polymers in pore space regions (framework walls, pore surface, pore interior) of mesoporous nanocarriers with large surface areas and pore volumes has attracted considerable attention in drug delivery. The system constitutes great advances in multivalent specific interactions which increase the host-guest affinity or avidity in the confined pore space. Herein, we present and discuss the recent advances in the covalent and noncovalent incorporation of polymers into mesopores for drug-oriented delivery systems. The present challenges and new approaches towards functional drug-polymer-inorganic mesostructured hybrids are reviewed for a deeper understanding of the synergy of functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7tb02559aDOI Listing
December 2017

NIR light-activated dual-modality cancer therapy mediated by photochemical internalization of porous nanocarriers with tethered lipid bilayers.

J Mater Chem B 2017 Nov 25;5(42):8289-8298. Epub 2017 Oct 25.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

To overcome endo/lysosomal restriction as well as to increase the clinical availability of nanomedicine, we report on a NIR stimuli-responsive nanoplatform based on mesoporous silica nanoparticles tethered with lipid bilayers (MSN@tLB) for chemotherapy and photodynamic dual-modality therapy. In this nanosystem, a hydrophilic drug molecule zoledronic acid (ZOL) was first incorporated into the MSN core with modifications of hyperbranched polyethylenimine (PEI). To prevent the leakage of the payload, the LB shell was covalently tethered onto the MSN core via the PEI cushion which can greatly enhance the stability of the LB. Meanwhile, a hydrophobic photosensitizer IR-780 iodide was introduced into the hydrophobic compartment to endow the system with photo-activation properties. The as-prepared MSN-ZOL@tLB-IR780 possesses high dispersion stability stemming from the LB, as well as negligible cytotoxicity. After cellular internalization and endo/lysosomal capture of the nanoparticles, photochemical internalization (PCI) mediated simultaneous cargo release and endo/lysosomal escape were achieved by local ROS production upon 808 nm irradiation, thus leading to highly efficient chemo-photodynamic therapy on cancer cells in vitro. Such a system presents a sophisticated platform that integrates biocompatibility, spatiotemporal control, NIR-responsiveness, and synergistic therapies to promote cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7tb02095cDOI Listing
November 2017

Lipid Bilayer-Gated Mesoporous Silica Nanocarriers for Tumor-Targeted Delivery of Zoledronic Acid in Vivo.

Mol Pharm 2017 09 10;14(9):3218-3227. Epub 2017 Aug 10.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University , Turku 20520, Finland.

Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate used for the treatment of bone diseases and calcium metabolism. Anticancer activity of ZOL has been established, but its extraskeletal effects are limited due to its rapid uptake and accumulation to bone hydroxyapatite. In this work, we report on the development of tethered lipid bilayer-gated mesoporous silica nanocarriers (MSNs) for the incorporation, retention, and intracellular delivery of ZOL. The in vitro anticancer activity of ZOL-loaded nanocarriers was evaluated by cell viability assay and live-cell imaging. For in vivo delivery, the nanocarriers were tagged with folic acid to boost the affinity for breast cancer cells. Histological examination of the liver revealed no adverse off-target effects stemming from the nanocarriers. Importantly, nonspecific accumulation of ZOL within bone was not observed, which indicated in vivo stability of the tethered lipid bilayers. Further, the intravenously administered ZOL-loaded nanocarriers showed tumor growth suppression in breast cancer xenograft-bearing mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.7b00519DOI Listing
September 2017

Fluorescent miRNA analysis enhanced by mesopore effects of polydopamine nanoquenchers.

Analyst 2017 Jul;142(15):2796-2804

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

The combination of fluorophore-labelled single-strand DNA probes and nanomaterial quenchers has shown great potential in miRNA detection. The development of advanced detection systems by understanding and controlling the fluorescence quenching/recovery via nanoquenchers' microstructures and local morphologies is an attractive area warranting further investigations. Inspired by nanopore sequencing, we present a novel miRNA sensing strategy using fluorophore-labeled DNA as probes and a type of large-pore-sized mesoporous polydopamine nanoparticles (MPDA-L, 70 nm in diameter) as fluorescence quenchers. It is revealed that the quenching efficiency of MPDA-L towards the fluorophore labelled on the probe, reached more than 99% at a relatively low particle concentration. Moreover, the mesopores effectively protected the probe DNA from cleavage by DNase I which was used for signal amplification. Sensitive detection of miRNA with a low detection limit of 32-40 pM, as well as a linear detection range of up to 5 nM, was realized by the mesopore effects via a greatly improved differential affinity of ssDNA and the probe-miRNA heteroduplex toward the surface of nanoquenchers. Interestingly, enhanced DLVO (Derjaguin-Landau-Verwey-Overbeek) repulsion generated inside the pore surface by the negative surface-curvature effect correlates with the improved duplex detachment and fluorescence recovery. The developed strategy can be successfully applied to quantify down-regulated let-7a and up-regulated miRNA-21 in different types of cancer cells by using total RNA samples from cell lysate. These findings are expected to inspire strategies and pave a way for utilizing porous nanomaterials for constructing miRNA detection systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7an00528hDOI Listing
July 2017

Mesoporous polydopamine nanoparticles with co-delivery function for overcoming multidrug resistance via synergistic chemo-photothermal therapy.

Nanoscale 2017 Jun;9(25):8781-8790

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Theranostic agents for combined chemo-photothermal therapy have attracted intensive interest in the treatment of multi-drug resistance (MDR) in cancer therapy. However, the development of simple theranostic agents as dual hosts for both heat and a high payload of chemotherapeutic agents remains a big challenge. Herein, mesoporous polydopamine nanoparticles (MPDA) were successfully developed with properties of a high payload of DOX (up to 2000 μg mg) and the drug efflux inhibitor TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate), as well as strong near-infrared absorption. Particularly, DOX and TPGS were sequentially loaded in the pore space and on the external particle surface of MPDA via π-π stacking and hydrophobic interactions, resulting in a MPDA-DOX@TPGS complex. The DOX release observably relies on the pH value and glutathione (GSH). Furthermore, it is possible to accelerate the rate of drug release by NIR irradiation. Importantly, the MPDA-DOX@TPGS complex was found to escape from endosomes after cellular uptake and release the loaded drugs into the cytosol. By TPGS mediated MDR reversal, the delivered DOX induced significant cytotoxicity to MCF-7/ADR cells. Besides, MPDA can absorb the NIR light and convert it into fatal heat to kill the cancer cells. As a consequence, the combined therapy in our system yields a synergistic effect with high therapeutic efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7nr01857fDOI Listing
June 2017

Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery.

Int J Nanomedicine 2016;11:6591-6608. Epub 2016 Dec 8.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University.

Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g). The developed nanocarriers were efficiently taken up by cancer cells and were subsequently able to escape to the cytoplasm from the endosomes, most likely owing to the integrated PEI. Triggered by the intracellular redox conditions, the siRNA was sustainably released inside the cells over a period of several days. Functionality of siRNAs was demonstrated by using cell-killing siRNA as cargo. Despite not being the aim of the developed system, in vitro experiments using cell-killing siRNAs showed that the efficacy of siRNA transfection was comparable to the commercial in vitro transfection agent Lipofectamine. Consequently, the developed MSN-based delivery system offers a potential approach to hybrid nanocarriers for more efficient and long-term siRNA delivery and, in a longer perspective, in vivo gene silencing for RNA interference (RNAi) therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S120611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154729PMC
February 2017

Nanoscale Polydopamine (PDA) Meets π-π Interactions: An Interface-Directed Coassembly Approach for Mesoporous Nanoparticles.

Langmuir 2016 11 10;32(46):12119-12128. Epub 2016 Nov 10.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , No. 174 Shazheng Road, Chongqing 400044, China.

Well known for the adhesive property, mussel-inspired polydopamine (PDA) has been shown to enhance performance in a wide range of adsorption-based applications. However, imparting porous nanostructures to PDA materials for enhanced loading capacities has not been demonstrated even when surfactants were present in the synthesis. Herein, we report on the preparation of mesoporous PDA particles (MPDA) based on the assembly of primary PDA particles and Pluronic F127 stabilized emulsion droplets on water/1,3,5-trimethylbenzene (TMB) interfaces. The key to the formation of this new type of the MPDA structure is the full utilization of the π-π stacking interactions between PDA structures and the π-electron-rich TMB molecules. Remarkably, this method presents a facile approach for MPDA particles with an average diameter of ∼90 nm, slit-like pores with a peak size of ∼5.0 nm as well as hollow cavities. When used as the adsorbent for a model dye RhB, the MPDA particles achieved an ultrahigh RhB adsorption capacity of 1100 μg mg, which is significantly higher than that for the PDA-reactive dyes with Eschenmoser structure. Moreover, it was demonstrated that the cavity space in MPDA can facilitate high volumetric uptake in a capillary filling/stacking manner via the π-π interactions. These developments pave a new avenue on the mechanism and the designed synthesis of functional PDA materials by organic-organic composite assembly for advanced adsorption applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.6b03294DOI Listing
November 2016

Silica-assisted incorporation of polydopamine into the framework of porous nanocarriers by a facile one-pot synthesis.

J Mater Chem B 2016 Apr 21;4(14):2435-2443. Epub 2016 Mar 21.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Mussel-inspired polydopamine (PDA), with its advanced bio-adhesive properties, has shown great potential in drug delivery based on host-guest interaction. However, it is difficult to synthesize PDA NPs of high surface area using the traditional polymerization of dopamine monomers in an alkaline solution. Taking advantage of the interaction between PDA and silicic acid inspired by biosilicification, PDA was rendered with high surface area in 70 nm-sized hybrid porous particles by a silica assisted one-pot preparation. PDA building blocks were successfully incorporated into the silica framework by controlled addition of dopamine (1.25-5 mol% with respect to the silica source) in a typical synthesis of mesoporous silica nanoparticles (MSNs). It is revealed that the cooperative molecular interaction between silicic acid and catechol groups of PDA results in a retardation of the silica condensation during the particle formation process. Moreover, the replacement of dopamine with polyphenols such as epigallocatechin gallate (EGCG) or tannic acid (TA) resulted in complete phase separation of the polymer and silica at the same molar ratio, suggesting the important role of amines in PDA towards stable hybridization in the particles. The application potential of the PDA-MSN hybrid nanocarriers is demonstrated by an unprecedentedly high drug (DOX) loading capacity of 1000 mg g, a sustained drug release, as well as enhanced killing efficiency of cancer cells at low dosage. These findings are expected to inspire strategies and pave a way for utilizing PDA for constructing organic-inorganic composite nanocarriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5tb02784eDOI Listing
April 2016

Modulation of the structural properties of mesoporous silica nanoparticles to enhance the T-weighted MR imaging capability.

J Mater Chem B 2016 Mar 12;4(9):1720-1732. Epub 2016 Feb 12.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

In this study, we have investigated the contrast enhancement of Gd(iii) incorporated nanoparticle-based contrast agents (CA) by the modulation of the synthesis and structural parameters of the mesoporous silica nanoparticle (MSN) matrix. In the optimisation process, the structure of the MSN matrix, post-synthesis treatment protocols, as well as the source and incorporation routes of paramagnetic gadolinium centers were considered, with the aim to shorten the T weighted relaxation time. After preliminary evaluation of the prepared MSNs as nanoparticulate T/positive contrast agents based on relaxivity, the structure of the MSN matrix was affirmed as the most decisive property to enhance the r relaxivity value, alongside the incorporation route of paramagnetic Gd(iii) centers. Based on these findings, the most promising Gd(iii) incorporated MSN-based CA candidate was further evaluated for its cytocompatibility and intensity enhancement by in vitro phantom MR-imaging of labeled cells. Furthermore, pre-labeled tumors grown on a chick embryo chorioallantoic membrane (CAM) were imaged as an in vivo model on a 3T clinical MRI scanner. Our findings show that the optimized MSN-based CA design enables proper access of water to Gd-centers in the selected MSN matrices, and simultaneously decreases the required amount of Gd(iii) content per mass when evaluated against the other MSNs. Consequently, the required Gd amount on a per-dose basis is significantly decreased with regard to clinically used Gd-based CAs for T-weighted MR imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5tb02371hDOI Listing
March 2016

Mesoporous silica nanoparticles in tissue engineering--a perspective.

Nanomedicine (Lond) 2016 Feb 19;11(4):391-402. Epub 2016 Jan 19.

Turku Centre for Biotechnology, University of Turku & Åbo Akademi University, FI-20520 Turku, Finland.

In this review, we summarize the latest developments and give a perspective on future applications of mesoporous silica nanoparticles (MSNs) in regenerative medicine. MSNs constitute a flexible platform for controlled delivery of drugs and imaging agents in tissue engineering and stem cell therapy. We highlight the recent advances in applying MSNs for controlled drug delivery and stem cell tracking. We touch upon novel functions of MSNs in real time imaging of drug release and biological function, and as tools to control the chemical and mechanical environment of stem cells. We discuss the need for novel model systems for studying biofunctionality and biocompatibility of MSNs, and how the interdisciplinary activities within the field will advance biotechnology research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nnm.15.212DOI Listing
February 2016

Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy.

Biomaterials 2016 Mar 6;83:51-65. Epub 2016 Jan 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China. Electronic address:

To efficiently deliver anti-cancer drug to tumor site and reduce its toxic side effects on normal tissues, a polyethylene glycol (PEG) shielding and tumor microenvironment triggering cascade pH-responsive hollow mesoporous silica nanoparticles (HMSNs) drug delivery system was fabricated. 3-(3, 4-dihydroxyphenyl) propionic acid (DHPA) functionalized beta-cyclodextrin (β-CD) was grafted onto the surfaces of HMSNs via boronic acid-catechol ester bonds. Then, PEG conjugated adamantane (Ada) was anchored on HMSNs-β-CD nanocarrier via host-gust interaction. Various techniques proved the successful fabrication of the system. The in vitro tests confirmed that the system was biocompatible. After the system permeating into tumor via enhanced permeability and retention (EPR) effect, the benzoic-imine bonds between the PEG and Ada were cleaved under weak acid condition in tumor microenvironment (pH 6.8), while the dissociated PEG protective layer facilitating cellular uptake of HMSNs system. Subsequently, the boronic acid-catechol ester bonds linkers further hydrolyzed under even low endosomal pH (4.5-6.5) condition for intracellular drug delivery, leading to efficient cell apoptosis. The in vivo results demonstrated that drug loaded HMSNs significantly inhibited tumor growth while only with minimal toxic side effects. The strategy provides new insight into the development of new generation of drug delivery carriers triggering by tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2016.01.008DOI Listing
March 2016

The viability of mesoporous silica nanoparticles for drug delivery.

Ther Deliv 2015 14;6(8):891-3. Epub 2015 Aug 14.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/TDE.15.46DOI Listing
July 2016

Combination of magnetic field and surface functionalization for reaching synergistic effects in cellular labeling by magnetic core-shell nanospheres.

Biomater Sci 2014 Dec 6;2(12):1750-1760. Epub 2014 Aug 6.

Laboratory for Physical Chemistry, Åbo Akademi University, Porthansgatan 3, 20500 Turku, Finland.

Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, core-shell structured sandwich-like magnetic mesoporous silica nanospheres were developed. While the magnetite cluster core can provide a high magnetic response for overcoming Brownian motion in cell culture media, the layered silica shell facilitates an efficient fluorescent dye labeling. However, the problem of particle aggregation in cell media, which is strongly enhanced under a magnetic field, significantly impeded the uptake by cells, resulting in difficulties in the precise analysis of the degree of particle internalization by fluorescence-based techniques (flow cytometry and confocal microscopy). To overcome this, reflection-based assessment was employed. Further, emphasis was put on utilizing the unique role of surface-hyperbranched polyethylenimine (PEI) in efficient prevention of particle aggregation prior to cell internalization in the presence of an external magnetic field. The interparticle attraction forces originating from magnetic dipole-dipole interactions are hereby balanced by the steric and electrostatic repulsion forces provided by the PEI functionalization, which leads to dispersed nanospheres in cell culture media during the magnetic-field induced cell labeling. As a consequence, PEI functionalization and the presence of the magnetic field synergistically enhanced the efficiency of MRI-fluorescence dual-mode labeling for cellular tracking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c4bm00221kDOI Listing
December 2014