Publications by authors named "Tianqing Liu"

128 Publications

Topically applied liposome-in-hydrogels for systematically targeted tumor photothermal therapy.

Drug Deliv 2021 Dec;28(1):1923-1931

School of Pharmacy, Nantong University, Nantong, China.

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.
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http://dx.doi.org/10.1080/10717544.2021.1974607DOI Listing
December 2021

A biological functional hybrid scaffold based on decellularized extracellular matrix/gelatin/chitosan with high biocompatibility and antibacterial activity for skin tissue engineering.

Int J Biol Macromol 2021 Sep 30;187:840-849. Epub 2021 Jul 30.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Nowadays, decellularized extracellular matrix (dECM) has received widespread attention due to its diversity in providing the unique structural and functional components to support cell growth, and finding material with good biocompatibility and anti-infection capability for skin tissue engineering is still a challenge. In this study, a novel dECM/Gel/CS scaffold with appropriate mechanical strength, good antibacterial activity and high biocompatibility was prepared using a one-pot method. The results showed that the immune components such as cells and DNA (about 98.1%) were successfully removed from the porcine skin tissue. The dECM/Gel/CS scaffolds exhibited an interconnected pore structure and had a high porosity (>90%) to promote cell growth. Moreover, the appropriate elastic modulus (≥482.17 kPa) and degradability (≥80.04% for 15 days) of the scaffolds offered stout "houses" for cell proliferation and suitable degradation rate to match the new tissue formation in skin tissue engineering. Furthermore, the addition of chitosan endowed the scaffold with good antibacterial activity, water and protein absorption capacity to avoid wound infection, and maintain the moisture and nutrition balance. In vitro cytocompatibility studies showed that the presence of dECM effectively enhanced the cell proliferation. Overall, the advanced dECM/Gel/CS scaffold has considerable potential to be applied in skin tissue engineering.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.162DOI Listing
September 2021

Ferroptosis-Strengthened Metabolic and Inflammatory Regulation of Tumor-Associated Macrophages Provokes Potent Tumoricidal Activities.

Nano Lett 2021 08 22;21(15):6471-6479. Epub 2021 Jul 22.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, People's Republic of China.

Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. However, there are a few strategies that can simultaneously regulate both inflammatory and metabolic functions to achieve safe and potent antitumor activation of TAMs. Herein, we demonstrate that an iron-based metal organic framework nanoparticle and a ferroptosis-inducing agent synergistically induce mitochondrial alternation in TAMs, resulting in a radical metabolic switch from mitochondrial oxidative phosphorylation to glycolysis, which is resistant to anti-inflammatory stimuli challenge. The ferroptosis stress strengthened by the nanoformulation also drives multiple pro-inflammatory signaling pathways, enabling macrophage activation with potent tumoricidal activities. The ferroptosis-strengthened macrophage regulation strategy present in this study paves the way for TAM-centered antitumoral treatment to overcome the limitations of conventional methods.
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http://dx.doi.org/10.1021/acs.nanolett.1c01401DOI Listing
August 2021

Biomimetic recombinant of red blood cell membranes for improved photothermal therapy.

J Nanobiotechnology 2021 Jul 18;19(1):213. Epub 2021 Jul 18.

School of Pharmacy, Nantong University, 226001, Nantong, China.

Background: RBC membrane derived nanoparticles (NPs) represent an emerging platform with prolonged circulation capacity for the delivery of active substances. For functionalize derived RBCs NPs, various strategies, such as biomimetic rebuilding of RBCs, chemical modification or inserting ligands, have been carried out to improve their performance. However, one potential adverse effect for these methods is the structural failure of membrane proteins, consequently affecting its original immune escape function.

Results: In this study, we reported a green technology of "disassembly-reassembly" to prepare biomimetic reconstituted RBCs membrane (rRBCs) by separating the endogenous proteins and lipids from nature RBC membrane. IR780 iodide was used as a pattern drug to verify the property and feasibility of rRBCs by constructing [email protected] NPs with [email protected] NPs and free IR780 as controls. The results demonstrated the superiority of [email protected] NPs in toxicity, stability, pharmacokinetics and pharmacodynamics compared with [email protected] and free IR780.

Conclusions: The reported "disassembly-reassembly" strategy shows great potential to produce controllable and versatile rRBC membrane-inspired delivery platform, which may be used to overcome the deficiency of functionalization in cell membrane coated nanoparticles .
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http://dx.doi.org/10.1186/s12951-021-00949-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286575PMC
July 2021

Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.

J Mater Chem B 2021 Jul;9(26):5365-5373

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, VIC 3052, Australia. and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, VIC 3052, Australia.

Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.
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http://dx.doi.org/10.1039/d1tb00721aDOI Listing
July 2021

Validation of the mechano-bactericidal mechanism of nanostructured surfaces with finite element simulation.

Colloids Surf B Biointerfaces 2021 Oct 16;206:111929. Epub 2021 Jun 16.

School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, Liaoning Province, PR China.

The mechano-bactericidal property of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, especially in the current era of spreading antibiotic resistance. However, the mechanisms underlying nanostructured surfaces mechanically damaging bacteria remain unclear, which ultimately limits translational potential toward real-world applications. Using finite element simulation technique, we developed the three-dimensional thin wall with turgor pressure finite element model (3D-TWTP-FEM) of bacterial cell and verified the reliability of this model by the AFM indentation experiment simulation of the cell, and the cell model is able to simulate suspended bacterial cell and the process of cell adhering to the flat and nanopillar surfaces. Since bacterial cells suffer greater stress and deformation on the nanopillar surfaces, a two-stage model of the elastic and creep deformation stage of the cells on the nanostructured surfaces was developed. The calculations show that the location of the maximum stress/strain on the cells adhered to the nanopillar surfaces is at the liquid-cell-nanopillar three phase contact line. The computational results confirmed the ability of nanostructured surfaces to mechanically lyse bacteria and gave the effect of nanopillar geometry on the efficiency and speed of bacterial cell rupture. This study provides fundamental physical insights into how nanopillar surfaces can serve as effective and fast mechanical antimicrobial materials.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111929DOI Listing
October 2021

Low-Temperature Hydrothermal Synthesis of Novel 3D Hybrid Nanostructures on Titanium Surface with Mechano-bactericidal Performance.

ACS Biomater Sci Eng 2021 06 20;7(6):2268-2278. Epub 2021 May 20.

School of Chemical Engineering, Dalian University of Technology, Dalian 116024, Liaoning, P. R. China.

Titanium is extensively employed in modern medicines as orthopedic and dental implants, but implant failures frequently occur because of bacterial infections. Herein, three types of 3D nanostructured titanium surfaces with nanowire clusters (NWC), nanowire/sheet clusters (NW/SC) and nanosheet clusters (NSC), were fabricated using the low-temperature hydrothermal synthesis under normal pressure, and assessed for the sterilization against two common human pathogens. The results show that the NWC and NSC surfaces merely display good bactericidal activity against , whereas the NW/SC surface represents optimal bactericidal efficiency against both (98.6 ± 1.23%) and (69.82 ± 2.79%). That is attributed to the hybrid geometric nanostructure of NW/SC, i.e., the pyramidal structures of ∼23 nm in tip diameter formed with tall clustered wires, and the sharper sheets of ∼8 nm in thickness in-between these nanopyramids. This nanostructure displays a unique mechano-bactericidal performance via the synergistic effect of capturing the bacteria cells and penetrating the cell membrane. This study proves that the low-temperature hydrothermal synthesized hybrid mechano-bactericidal titanium surfaces provide a promising solution for the construction of bactericidal biomedical implants.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01659DOI Listing
June 2021

Photoactivatable nanogenerators of reactive species for cancer therapy.

Bioact Mater 2021 Dec 29;6(12):4301-4318. Epub 2021 Apr 29.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O ), nitric oxide (NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.
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http://dx.doi.org/10.1016/j.bioactmat.2021.04.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105601PMC
December 2021

Protein corona precoating on redox-responsive chitosan-based nano-carriers for improving the therapeutic effect of nucleic acid drugs.

Carbohydr Polym 2021 Aug 16;265:118071. Epub 2021 Apr 16.

School of Pharmacy, Nantong University, No. 19 Qixiu Road, Nantong, 226001, China. Electronic address:

Spontaneous formation of protein corona on chitosan-based nano-carriers is inevitable once they enter the blood, which is considered to be an important factor that weakens the delivery efficiency and therapeutic effect of nucleic acid drugs. For this, cyclic RGDyK peptide (cRGD) modified bovine serum albumin (BSA) was designed as a corona to precoat on redox-responsive chitosan-based nano-carriers (TsR NPs) before administration. The effects of the precoating corona on the pharmaceutical properties and delivery efficiency of the nano-carriers and the therapeutic effect of model siRNA (siVEGF) were investigated. The results showed that BSA-cRGD formed steady corona around TsR NPs, which enhanced targeting ability to cancer cells and reduced serum proteins adsorption. The Bc corona improved the stability and biocompatibility of TsR NPs, increased the intracellular uptake, facilitated the lysosomal escape and maintained their redox-sensitive responsiveness, resulting in enhanced gene silencing efficiency and anti-tumor proliferation effects both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.carbpol.2021.118071DOI Listing
August 2021

KSO-mediated regio- and stereo-selective thiocyanation of enamides with NHSCN.

Org Biomol Chem 2021 03 4;19(11):2512-2516. Epub 2021 Mar 4.

School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, People's Republic of China.

A direct and straightforward thiocyanation of enamides with NHSCN under metal-free conditions has been accomplished. A variety of (E)-β-thiocyanoenamides are readily produced in a regio- and stereo-selective manner. The protocol features mild reaction conditions, good functional group tolerance and operational simplicity. The potential utility of this strategy was further demonstrated by transformation of thiocyanate into thiotetrazole-containing compounds and a Pd-catalyzed cross-coupling reaction to afford six- or seven-membered sulfur-containing heterocycles. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.
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http://dx.doi.org/10.1039/d1ob00156fDOI Listing
March 2021

Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney.

Front Oncol 2020 8;10:609839. Epub 2021 Jan 8.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.
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http://dx.doi.org/10.3389/fonc.2020.609839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873889PMC
January 2021

Evaluation of anti-tumor effects of crocin on a novel 3D tissue-engineered tumor model based on sodium alginate/gelatin microbead.

Int J Biol Macromol 2021 Mar 30;174:339-351. Epub 2021 Jan 30.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Crocin, as one of the biologically active components of saffron, has anti-inflammatory, anti-oxidant, anti-depressant and auxiliary anti-tumor effects. Studies have shown that crocin could promote breast cancer cell apoptosis. However, conventional methods are mainly based on two-dimensional (2D) cell culture models, which are difficult to reproduce the tumor environment in vivo due to space constraints. In this study, we prepared a three-dimensional (3D) cell model in vitro based on sodium alginate/gelatin to evaluate the inhibitory effect of crocin on MCF-7 cells, which could bridge the gap in crocin drug evaluation between 2D and 3D cell model in vitro. Different from the 2D culture, the cells were found to aggregate in a spherical shape in the 3D microgel beads. And the CCK-8 assay showed that the growth of MCF-7 cells exposed to crocin was inhibited in a time-related and concentration-related manner. Compared with 2D culture (IC that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 3.68, 2.55 and 1.53 mg/mL, respectively), the IC value of 3D culture (IC that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 10.12, 6.89 and 6.64 mg/mL, respectively) was significantly increased by 2.77, 2.70, 4.34 times, respectively. Besides, live/dead staining and scanning electron microscope (SEM) revealed that the 2D cultured cells shrank and ruptured after crocin treatment, and the number of living cells was considerably reduced; the size of the cell colonies in the 3D microgel beads decreased.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.181DOI Listing
March 2021

Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial-Mesenchymal Transition.

Front Chem 2020 15;8:601649. Epub 2021 Jan 15.

NICM Health Research Institute, Western Sydney University, Sydney, NSW, Australia.

Malignant cancer is a devastating disease often associated with a poor clinical prognosis. For decades, modern drug discoveries have attempted to identify potential modulators that can impede tumor growth. Cancer stem cells however are more resistant to therapeutic intervention, which often leads to treatment failure and subsequent disease recurrence. Here in this study, we have developed a specific multi-target drug delivery nanoparticle system against breast cancer stem cells (BCSCs). Therapeutic agents curcumin and salinomycin have complementary functions of limiting therapeutic resistance and eliciting cellular death, respectively. By conjugation of CD44 cell-surface glycoprotein with poly(lactic-co-glycolic acid) (PLGA) nanoparticles that are loaded with curcumin and salinomycin, we investigated the cellular uptake of BCSCs, drug release, and therapeutic efficacy against BCSCs. We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G cell cycle arrest and limiting epithelial-mesenchymal transition. This curcumin and salinomycin co-delivery system can be an efficient treatment approach to target malignant cancer without the repercussion of disease recurrence.
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http://dx.doi.org/10.3389/fchem.2020.601649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843432PMC
January 2021

Evaluation of inhibitory effects of geniposide on a tumor model of human breast cancer based on 3D printed Cs/Gel hybrid scaffold.

Mater Sci Eng C Mater Biol Appl 2021 Feb 11;119:111509. Epub 2020 Sep 11.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Traditional Chinese medicine therapy, which can serve as adjuvant therapy for cancer treatment, has no obvious side effects on the human body. Geniposide (GEN), one of the main iridoid glycosides in gardenia fruit, has been widely reported to have anti-cancer effects. In this study, we aimed to inspect whether GEN could inhibit proliferation and promote the apoptosis of human breast cancer cells (MCF-7). In order to better predict the efficacy of GEN, we have prepared the Cs/Gel composite scaffolds by 3D printing technology to mimic the MCF-7 cell growth microenvironment. The prepared Cs/Gel scaffold has good mechanical properties and biocompatibility, which can provide a more accurate platform for drug screening. The semi-inhibitory concentration (IC50) evaluated by CCK-8 assay was 16.06 mg/mL (24 h), 14.85 mg/mL (48 h), and 13.14 mg/mL (72 h). After exposed to GEN for 48 h, the cancer cell survival rate reduced from 69.15 ± 2.86% (13 mg/mL) to 20.97 ± 3.24% (16 mg/mL). Although the inhibitory effect was weaker in the 3D culture system, it also managed to inhibit cell proliferation and induce cell apoptosis. Besides, Live/Dead staining, Hematoxylin-Eosin (H&E) staining and SEM evaluation were also conducted to estimate the anti-cancer effect of GEN in 2D and 3D cultures. The results indicate that GEN has an anti-cancer effect based on a time- and dose-dependent manner.
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http://dx.doi.org/10.1016/j.msec.2020.111509DOI Listing
February 2021

Virus Mimetic Shell-Sheddable Chitosan Micelles for siVEGF Delivery and FRET-Traceable Acid-Triggered Release.

ACS Appl Mater Interfaces 2020 Nov 17. Epub 2020 Nov 17.

Department of Pharmaceutics, School of Pharmacy, Nantong University, Nantong 226001, China.

Targeting vascular endothelial growth factor (VEGF) using small interfering RNA (siVEGF) has shown great potential in inhibiting the growth, proliferation, and migration of tumors by reducing the proliferation of blood vessels. On the basis of bionic principles, a novel pH-responsive and virus mimetic shell-sheddable chitosan (CS) micelles (CMs) as siRNA delivery system was introduced in this study. The cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) modified poly(enthylene glycol) (PEG) was conjugated to the HA2 modified chitosan via a hydrazone linkage (cRGD-PEG-Hz-CS-HA2). The cRGD-PEG-Hz-CS-HA2 conjugate could form micelles by interacting with the complex of octanal, Boc-l-lysine, and 9-d-arginine (9R) (octyl-Lys-9R) as a hydrophodic core forming agent, termed as cRGD-PEG-Hz-CS-HA2/octyl-Lys-9R (abbreviated as cRGD/HA2/Hz-CMs).The CMs modified with cRGD can accurately target glioma cells (U87MG cells) with high expression of αvβ3. The payloads of siVEGF were packed into the core of cRGD/HA2/Hz-CMs via electrostatic interaction and hydrophobic interaction. The intracellular cargo release was achieved by the pH-responsive lysis of the hydrazone bond in acidic environment of endosome. Moreover, the exposed HA2, as a pH-sensitive membrane-disruptive peptide, assists the escape of the carriers from endosome into cytosol. In addition, cRGD/HA2/Hz-CMs can effectively deliver siVEGF and silence VEGF gene expression in U87MG cells, leading to the significant tumor growth inhibition. This study demonstrates that cRGD/HA2/Hz-CMs can deliver and release siVEGF in a controlled manner, which was traced by the fluorescence resonance energy transfer (FRET) system in order to achieve RNAi-based anti-angiogenic treatment of cancer in vivo.
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http://dx.doi.org/10.1021/acsami.0c13023DOI Listing
November 2020

Preparation, characterization and antioxidant activity of protocatechuic acid grafted carboxymethyl chitosan and its hydrogel.

Carbohydr Polym 2021 Jan 13;252:117210. Epub 2020 Oct 13.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China; Research & Educational Center for the Control Engineering of Translational Precision Medicine (R-ECCE-TPM), School of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian 116024, China.

In this study, protocatechuic acid (PCA) was grafted onto carboxymethyl chitosan (CMCS) via EDC/NHS to improve the antioxidant effect. The grafting ratio of PCA-g-CMCS conjugates could be controlled by adjusting the pH value and feed ratio of raw materials. The conjugates exhibited similar pH sensitivity to CMCS and showed dramatic enhancements of DPPH and ABTS radicals scavenging activities, total antioxidant capacity, reducing power, and Fe-chelating activity. Three-dimensional porous PCA-g-CMCS hydrogel was prepared by lyophilization and secondary cross-linking. The shaped hydrogel preserved its antioxidant activity, and the sustained release of PCA-containing degraded fragment from biodegradable hydrogel could be achieved with the aid of lysozyme in vitro (15 days). PCA-g-CMCS hydrogel also showed excellent biocompatibility and protective effect on HO-induced oxidative damage in SH-SY5Y cells. These results suggested that PCA-g-CMCS conjugates and its hydrogel would appear to be a promising oxidation-resistant material for applications such as drug release and tissue engineering.
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http://dx.doi.org/10.1016/j.carbpol.2020.117210DOI Listing
January 2021

Chitosan nanoparticles for oral photothermally enhanced photodynamic therapy of colon cancer.

Int J Pharm 2020 Nov 6;589:119763. Epub 2020 Sep 6.

School of Pharmacy, Nantong University, Nantong 226001, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Phototherapy exerts its anticancer effects by converting laser radiation energy into hyperthermia or reactive singlet oxygen (O). In this study, we developed chitosan nanoparticles (CS NPs) encapsulating both photothermal (IR780) and photodynamic (5-Aminolevulinic acid (5-ALA)) reagents for photothermally enhanced photodynamic therapy by noninvasive oral administration. The [email protected] NPs were stable in acidic conditions similar to the gastric environment, which greatly improved drug oral absorption and local accumulation in subcutaneous mouse colon tumors (CT-26 cells) following oral gavage. Mechanistic studies revealed that the co-delivery system can lead to photothermally enhanced photodynamic effects against cancer cells by increasing oxidative stress, including the elevation of ROS, superoxide and O production. Additionally, significant therapeutic efficacy for cancer treatment were observed in vivo after oral administration of [email protected] NPs, without causing any overt adverse effects. Our work highlights the great potential of photothermally enhanced photodynamic therapy by CS NPs for colon cancer management via oral route.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119763DOI Listing
November 2020

Multifunctional, durable and highly conductive graphene/sponge nanocomposites.

Nanotechnology 2020 Nov;31(46):465502

College of Aerospace Engineering, Shenyang Aerospace University, Shenyang 110136, People's Republic of China. Shenyang Aircraft Design Institute, Shenyang 110136, People's Republic of China.

Porous functional materials play important roles in a wide variety of growing research and industrial fields. We herein report a simple, effective method to prepare porous functional graphene composites for multi-field applications. Graphene sheets were non-chemically modified by TritonX-100, not only to maintain high structural integrity but to improve the dispersion of graphene on the pore surface of a sponge. It was found that a graphene/sponge nanocomposite at 0.79 wt.% demonstrated ideal electrical conductivity. The composite materials have high strain sensitivity, stable fatigue performance for 20 000 cycles, short response time of 0.401 s and fast response to temperature and pressure. In addition, the composites are effective in monitoring materials deformation and acoustic attenuation with a maximum absorption rate 67.78% and it can be used as electrodes for a supercapacitor with capacitance of 18.1 F g. Moreover, no expensive materials or complex equipment are required for the composite manufacturing process. This new methodology for the fabrication of multifunctional, durable and highly conductive graphene/sponge nanocomposites hold promise for many other applications.
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http://dx.doi.org/10.1088/1361-6528/ab9f73DOI Listing
November 2020

Advances in the Research of Bioinks Based on Natural Collagen, Polysaccharide and Their Derivatives for Skin 3D Bioprinting.

Polymers (Basel) 2020 May 29;12(6). Epub 2020 May 29.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.

The skin plays an important role in protecting the human body, and wound healing must be set in motion immediately following injury or trauma to restore the normal structure and function of skin. The extracellular matrix component of the skin mainly consists of collagen, glycosaminoglycan (GAG), elastin and hyaluronic acid (HA). Recently, natural collagen, polysaccharide and their derivatives such as collagen, gelatin, alginate, chitosan and pectin have been selected as the matrix materials of bioink to construct a functional artificial skin due to their biocompatible and biodegradable properties by 3D bioprinting, which is a revolutionary technology with the potential to transform both research and medical therapeutics. In this review, we outline the current skin bioprinting technologies and the bioink components for skin bioprinting. We also summarize the bioink products practiced in research recently and current challenges to guide future research to develop in a promising direction. While there are challenges regarding currently available skin bioprinting, addressing these issues will facilitate the rapid advancement of 3D skin bioprinting and its ability to mimic the native anatomy and physiology of skin and surrounding tissues in the future.
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http://dx.doi.org/10.3390/polym12061237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362214PMC
May 2020

Tuning of the Aggregation Behavior of Fluorinated Polymeric Nanoparticles for Improved Therapeutic Efficacy.

ACS Nano 2020 06 18;14(6):7425-7434. Epub 2020 May 18.

Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, United States.

Incorporation of fluorinated moieties in polymeric nanoparticles has been shown in many instances to increase their uptake by living cells and, hence, has proven to be a useful approach to enhancing delivery to cells. However, it remains unclear how incorporation of fluorine affects critical transport processes, such as interactions with membranes, intracellular transport, and tumor penetration. In this study, we investigate the influence of fluorine on transport properties using a series of rationally designed poly(oligo(ethylene glycol) methyl ether acrylate)--perfluoropolyether (poly(OEGA)-PFPE) copolymers. Copolymers with different fluorine contents were prepared and exhibit aggregate in solution in a manner dependent on the fluorine content. Doxorubicin-conjugated poly(OEGA)-PFPE nanoparticles with lower fluorine content exist in solution as unimers, leading to greater exposure of hydrophobic PFPE segments to the cell surface. This, in turn, results in greater cellular uptake, deeper tumor penetration, as well as enhanced therapeutic efficacy compared to that with the micelle-state nanoaggregates (poly(OEGA)-PFPE and poly(OEGA)-PFPE) with higher fluorine content but with less PFPE exposed to the cell membranes. Our results demonstrate that the aggregation behavior of these fluorinated polymers plays a critical role in internalization and transport in living cells and 3D spheroids, providing important design criteria for the preparation of highly effective delivery agents.
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http://dx.doi.org/10.1021/acsnano.0c02954DOI Listing
June 2020

Toxicological evaluation of ionic liquid in a biological functional tissue construct model based on nano-hydroxyapatite/chitosan/gelatin hybrid scaffolds.

Int J Biol Macromol 2020 May 5;158:800-810. Epub 2020 May 5.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

The application of ionic liquid is attracting more attentions as green replacement for volatile organic solvents. However, the toxic effects and risks of ionic liquid in different biological systems for human health and environment are poorly evaluated. Among all ionic liquids, 1-ethyl-3-methylimidazolium diethylphosphate ([Emim]DEP-type) ionic liquid is still at the early phase of development, and its toxicity remains unclear. In this study, we fabricated a 3D biological functional tissue construct model based on nano-hydroxyapatite, chitosan and gelatin hybrid scaffold and evaluated its toxic effects of [Emim]DEP-type ionic liquid. As a control group, the examination of ionic liquid's toxic effects on the pre-osteoblast cell line (MC3T3-E1) was detected in 2D cultures. The MTT assay showed that [Emim]DEP-type ionic liquid inhibited the proliferation of cells on both 2D cultures and 3D tissue constructs. This effect was correlated with culturing time and concentration, while the IC50 on 3D scaffolds (12,566, 9015, 7896 μg/mL, at 24 h, 48 h and 72 h, respectively) was found significantly higher compared to 2D cultures (3959, 2226, 1884 μg/mL). Flow cytometry analysis and scanning electron microscope demonstrated that when [Emim]DEP-type ionic liquid acted on MC3T3-E1 cells for 48 h, the shape of 2D cells shrank, together with decreased surface adhesion.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.04.267DOI Listing
May 2020

Postoperative delayed trapped temporal horn in patients with lateral ventricular trigone meningioma: Risk factors, surgical management, and literature review.

Eur J Surg Oncol 2020 12 24;46(12):2324-2330. Epub 2020 Apr 24.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address:

Object: To assess the risk factors for and surgical treatment of delayed trapped temporal horn (dTTH) in patients who had undergone removal of lateral ventricular trigone meningioma.

Method: Patients with lateral ventricular trigone meningioma treated at our institution from 2011 to 2015 were identified. Predictors for dTTH were determined using logistic regression. Literature review and pooled analysis were also conducted to evaluate the comparative effectiveness of surgical treatment for dTTH.

Results: A total of 110 cases were included in the analysis. Thirteen (11.8%) cases developed dTTH following surgery. Multivariable logistic regression demonstrated an association of longer operative duration with higher incidence of dTTH (OR, 1.34; 95% CI, 1.00-1.80; p = 0.049). As surgical duration prolonged from less than 3 hours to 5 hours or more, the incidence of dTTH increased in a consistent, linear fashion from 7.7% to 13.9% (p = 0.03). Six cases (46.2%, 6/13) of dTTH underwent surgical treatment for their life-threatening symptoms. Seven studies including 13 cases of dTTH in the literature were identified. Literature data, including the current series, revealed a total of 24 procedures were performed in 19 cases. Endoscopic fenestration trended toward fewer complications than shunt (7.7% vs 25.0%, p = 0.530). There were no significant differences in failure rates between the two groups (23.1% vs 25.0%, p = 1.000).

Conclusion: Patients with prolonged operative duration may be at higher risk of dTTH. Endoscopic fenestration is considered in preference to shunt placement, since it possesses equivalent success rates with fewer complications and avoids the need for a permanent implant.
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http://dx.doi.org/10.1016/j.ejso.2020.04.033DOI Listing
December 2020

A lightweight and low-cost electrode for lithium-ion batteries derived from paper towel supported MOF arrays.

Chem Commun (Camb) 2020 May 27;56(43):5847-5850. Epub 2020 Apr 27.

College of Materials Science and Engineering, Fuzhou University, Fujian 350108, China.

Herein, Cu-doped Co-ZIF nanoplate arrays are uniformly grown on a commercial paper towel substrate first. After a subsequent annealing treatment, well-defined Cu-doped Co/CoO nanoparticles embedded in N-doped carbon hybrid nanoplate arrays supported on the carbon paper substrate (denoted as Cu-doped Co/CoO/NC [email protected]) are obtained, which exhibit excellent performance as a low-cost, lightweight and binder-free anode for lithium ion storage.
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http://dx.doi.org/10.1039/d0cc01599gDOI Listing
May 2020

Engineering gelatin-based alginate/carbon nanotubes blend bioink for direct 3D printing of vessel constructs.

Int J Biol Macromol 2020 Feb 21;145:262-271. Epub 2019 Dec 21.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Nowadays 3D bioprinting, due to its high structural reconstruction and low cost, has been a promising technology and gained expectation in the treatment of vascular diseases. Although some studies have reported that 3D printing of large-sized blood vessels in the human body has been achieved, there are still some problems to be solved urgently, such as the unfulfilled microvascular simulation and inferior biocompatibility and mechanical strength of scaffold materials. In this paper, the hybrid bioink prepared with gelatin, sodium alginate and carbon nanotubes were manufactured into cylindrical scaffolds through the collaboration between the vertical directional extrusion of printing nozzle and axial rotation of stepper motor module. Mouse epidermal fibroblasts were inoculated into the inner and outer walls of hollow tubular scaffolds to fabricate engineered blood vessels. The internal diameters of the bionic circular tubes printed in batches were 3 mm with an average wall thickness of 0.5 mm and a length of 7-10 cm. Results demonstrated that the proper doping of carbon nanotubes could effectively increase the mechanical properties of the composite scaffolds. Also, quantitative experiments proved that a small amount of doping of carbon nanotubes had little effect on cytotoxicity, and the constructs could meet the requirements of biomimetic vascular.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.12.174DOI Listing
February 2020

Therapeutic "Tool" in Reconstruction and Regeneration of Tissue Engineering for Osteochondral Repair.

Appl Biochem Biotechnol 2020 Jun 21;191(2):785-809. Epub 2019 Dec 21.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.

Repairing osteochondral defects to restore joint function is a major challenge in regenerative medicine. However, with recent advances in tissue engineering, the development of potential treatments is promising. In recent years, in addition to single-layer scaffolds, double-layer or multilayer scaffolds have been prepared to mimic the structure of articular cartilage and subchondral bone for osteochondral repair. Although there are a range of different cells such as umbilical cord stem cells, bone marrow mesenchyml stem cell, and others that can be used, the availability, ease of preparation, and the osteogenic and chondrogenic capacity of these cells are important factors that will influence its selection for tissue engineering. Furthermore, appropriate cell proliferation and differentiation of these cells is also key for the optimal repair of osteochondral defects. The development of bioreactors has enhanced methods to stimulate the proliferation and differentiation of cells. In this review, we summarize the recent advances in tissue engineering, including the development of layered scaffolds, cells, and bioreactors that have changed the approach towards the development of novel treatments for osteochondral repair.
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http://dx.doi.org/10.1007/s12010-019-03214-8DOI Listing
June 2020

Dihydrolipoic Acid-Gold Nanoclusters Regulate Microglial Polarization and Have the Potential To Alter Neurogenesis.

Nano Lett 2020 01 6;20(1):478-495. Epub 2019 Dec 6.

Institute of Health and Biomedical Innovation , Queensland University of Technology , 60 Musk Avenue , Kelvin Grove, Brisbane , QLD 4059 , Australia.

Microglia-mediated neuroinflammation is one of the most significant features in a variety of central nervous system (CNS) disorders such as traumatic brain injury, stroke, and many neurodegenerative diseases. Microglia become polarized upon stimulation. The two extremes of the polarization are the neuron-destructive proinflammatory M1-like and the neuron-regenerative M2-like phenotypes. Thus, manipulating microglial polarization toward the M2 phenotype is a promising therapeutic approach for CNS repair and regeneration. It has been reported that nanoparticles are potential tools for regulating microglial polarization. Gold nanoclusters (AuNCs) could penetrate the blood-brain barrier and have neuroprotective effects, suggesting the possibility of utilizing AuNCs to regulate microglial polarization and improve neuronal regeneration in CNS. In the current study, AuNCs functionalized with dihydrolipoic acid (DHLA-AuNCs), an antioxidant with demonstrated neuroprotective roles, were prepared, and their effects on polarization of a microglial cell line (BV2) were examined. DHLA-AuNCs effectively suppressed proinflammatory processes in BV2 cells by inducing polarization toward the M2-like phenotype. This was associated with a decrease in reactive oxygen species and reduced NF-kB signaling and an improvement in cell survival coupled with enhanced autophagy and inhibited apoptosis. Conditioned medium from DHLA-AuNC-treated BV2 cells was able to enhance neurogenesis in both the neuronal cell line N2a and in an ex vivo brain slice stroke model. The direct treatment of brain slices with DHLA-AuNCs also ameliorated stroke-related tissue injury and reduced astrocyte activation (astrogliosis). This study suggests that by regulating neuroinflammation to improve neuronal regeneration, DHLA-AuNCs could be a potential therapeutic agent in CNS disorders.
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http://dx.doi.org/10.1021/acs.nanolett.9b04216DOI Listing
January 2020

Characterization and anti-tumor bioactivity of astragalus polysaccharides by immunomodulation.

Int J Biol Macromol 2020 Feb 24;145:985-997. Epub 2019 Oct 24.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address:

Astragalus polysaccharide (APS) has attracted growing interests in the field of anti-cancer by direct killing effect and improving immune function. In this study, the structure and composition of APS was determined, following the evaluation of in vitro and in vivo anti-tumor activity of APS targeted macrophages and host immune system based on immunoregulated strategy. The results indicated that APS had no direct cytotoxicity against 4T1 cells, but APS mediated macrophages could significantly inhibit the growth of 4T1 cells by the induction of cell cycle arrest (G2 phase) and cell apoptosis. APS mediated macrophages promoted the apoptosis of 4T1 cells mainly through the mitochondrial apoptosis pathway. The in vivo findings demonstrated that APS could markedly improve the thymus index and spleen index, and restore the structure of the damaged thymus and spleen tissue. APS could significantly enhance the proliferation of spleen lymphocytes and increase phagocytosis of peritoneal macrophages in mice. Furthermore, APS was capable of up-regulating the expression of IL-2, TNF-α and IFN-γ in peripheral blood. APS combined with 5-FU could improve the anti-tumor effect accompanied by the immunosuppressive alleviation of 5-FU on immune system, which may be suitable as an immune adjuvant for chemotherapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.09.189DOI Listing
February 2020

Remote Light-Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives.

Small 2019 11 10;15(45):e1903060. Epub 2019 Oct 10.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, QLD, 4072, Brisbane, Australia.

Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light-triggered DDS relies on processes of photolysis, photoisomerization, photo-cross-linking/un-cross-linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high-energy photons of UV/Vis light, recently nanocarriers have been developed based on light-response to low-energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light-triggered drug release systems are normally achieved by using two-photon absorption and photon upconversion processes. Herein, recent advances of light-responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR-light triggered drug delivery by two-photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.
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http://dx.doi.org/10.1002/smll.201903060DOI Listing
November 2019

3D Bio-Printing of CS/Gel/HA/Gr Hybrid Osteochondral Scaffolds.

Polymers (Basel) 2019 Sep 30;11(10). Epub 2019 Sep 30.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.

Cartilage is an important tissue contributing to the structure and function of support and protection in the human body. There are many challenges for tissue cartilage repair. However, 3D bio-printing of osteochondral scaffolds provides a promising solution. This study involved preparing bio-inks with different proportions of chitosan (Cs), Gelatin (Gel), and Hyaluronic acid (HA). The rheological properties of each bio-ink was used to identify the optimal bio-ink for printing. To improve the mechanical properties of the bio-scaffold, Graphene (GR) with a mass ratio of 0.024, 0.06, and 0.1% was doped in the bio-ink. Bio-scaffolds were prepared using 3D printing technology. The mechanical strength, water absorption rate, porosity, and degradation rate of the bio-scaffolds were compared to select the most suitable scaffold to support the proliferation and differentiation of cells. P3 Bone mesenchymal stem cells (BMSCs) were inoculated onto the bio-scaffolds to study the biocompatibility of the scaffolds. The results of SEM showed that the Cs/Gel/HA scaffolds with a GR content of 0, 0.024, 0.06, and 0.1% had a good three-dimensional porous structure and interpenetrating pores, and a porosity of more than 80%. GR was evenly distributed on the scaffold as observed by energy spectrum analyzer and polarizing microscope. With increasing GR content, the mechanical strength of the scaffold was enhanced, and pore walls became thicker and smoother. BMSCs were inoculated on the different scaffolds. The cells distributed and extended well on Cs/Gel/HA/GR scaffolds. Compared to traditional methods in tissue-engineering, this technique displays important advantages in simulating natural cartilage with the ability to finely control the mechanical and chemical properties of the scaffold to support cell distribution and proliferation for tissue repair.
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http://dx.doi.org/10.3390/polym11101601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835996PMC
September 2019

Mechanism Study of Bacteria Killed on Nanostructures.

J Phys Chem B 2019 10 8;123(41):8686-8696. Epub 2019 Oct 8.

School of Chemical Engineering , Dalian University of Technology , Dalian 116024 , Liaoning , P. R. China.

It is important to study the bactericidal mechanism with nanostructures for the design and preparation of high-efficiency sterilization materials. In this paper, the interfacial energy gradient between cells and nanopillars is proposed to be the driving force to promote cells to migrate into nanostructures and get killed. The expressions of interfacial energy and its gradient were first established, then the deformation of cells pressured by nanostructures was calculated. The results show that the interfacial energy gradient or the pressure on cells is influenced by nanopillar parameters substantially. The smaller the nanopillar diameter and the larger the pitch, the greater the pressure on cells. Only high enough nanocolumns can ensure sufficient cell creep deformation and become punctured. Furthermore, a cell volume and its adhesion morphology also influence the interaction between cells and nanostructures. The smaller the cell volume, the greater the pressure on it. And the larger the contact angle of adhered cells, the greater the pressure on the cells by nanopillars. Besides, the wettability of substrate material also influences the interaction between cells and nanopillars. It can be concluded that the model is reasonable and reliable since its calculation results are in good accordance with the experimental measurements.
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http://dx.doi.org/10.1021/acs.jpcb.9b07732DOI Listing
October 2019
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