Publications by authors named "Yuping Hong"

10 Publications

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Ultrasound-assisted CF-filled PLGA nanobubbles for enhanced FGF21 delivery and improved prophylactic treatment of diabetic cardiomyopathy.

Acta Biomater 2021 Aug 12;130:395-408. Epub 2021 Jun 12.

Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China.; Department of Ultrasound in Medicine, Shanghai Eighth People's Hospital, 8 Caobao Road, Shanghai 200235, PR China. Electronic address:

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (CF) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-emulsion evaporation and FGF21 was efficiently absorbed ([email protected]) via the electrostatic incorporation effect. [email protected] could effectively deliver FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared [email protected] could efficiently load FGF21 after doping with the cationic polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with CF, [email protected] could be used for distribution monitoring through ultrasound imaging. Moreover, [email protected] significantly downregulated the expression of ANP, CTGF, and caspase-3 mRNA via the action of LFUS owing to increased FGF21 release, therefore exhibiting enhanced inhibition of myocardial hypertrophy, apoptosis, and interstitial fibrosis in DCM mice. In conclusion, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. STATEMENT OF SIGNIFICANCE: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments. Fibroblast growth factor 21 (FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of FGF21 in DCM. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with FGF21 ([email protected]) were developed for the prophylactic treatment of DCM. [email protected] could effectively deliver the FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that [email protected] combined with LFUS could significantly down-regulate the expressions of ANP, CTGF, and caspase-3 mRNA, and as a result, it prevented the myocardial hypertrophy, apoptosis, and interstitial fibrosis of DCM mice. Overall, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.
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http://dx.doi.org/10.1016/j.actbio.2021.06.015DOI Listing
August 2021

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

ACS Biomater Sci Eng 2020 11 13;6(11):6276-6284. Epub 2020 Oct 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage . In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs cytotoxicity assays and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs . In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00724DOI Listing
November 2020

Integrating Epigenetic Modulators in Nanofibers for Synergistic Gastric Cancer Therapy via Epigenetic Reprogramming.

Nano Lett 2021 01 23;21(1):298-307. Epub 2020 Dec 23.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Epigenetic dysregulations resulting from the defects of epigenetic regulators are often reversible in tumorigenesis, making them promising cancer therapeutic targets. However, the limited specificity of action, short-term stability, and low retention of the epigenetic drugs greatly impede their clinical efficacy against solid tumors. Herein a method of combinatorial delivery of epigenetic modulatory drugs via a molecular self-assembly strategy was developed using inhibitors of DNA methyltransferases and histone deacetylases. The drug-drug conjugates can self-assemble into nanofibers with enhanced chemical stability. The nanofibers synergistically regulate aberrant DNA methylation and histone deacetylation, subsequently reprogram the gene expression profiles, and finally inhibit gastric cancer cell proliferation and promote cell apoptosis. The superior therapeutic efficacy of the nanofibers could be ascribed to the prolonged retention and accumulation in tumors and the minimized off-target effects. Therefore, this design of epigenetic-drug-based nanofiber formulation may provide a valuable paradigm for cancer therapy through epigenetic reprogramming.
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http://dx.doi.org/10.1021/acs.nanolett.0c03665DOI Listing
January 2021

A novel anticoagulant affinity membrane for enhanced hemocompatibility and bilirubin removal.

Colloids Surf B Biointerfaces 2021 Jan 22;197:111430. Epub 2020 Oct 22.

Institute of Nano Biomedicine and Engineering, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China; National Engineering Center for Nanotechnology, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Affinity membrane is widely employed to promote specific adsorption of toxins and reduce the blood purification therapeutic time. However, it suffers from insufficient toxin binding and low hemocompatibility. Herein, a novel anticoagulant affinity membrane (AAM) was developed to clear bilirubin from human blood in a pore-flow-through way. Firstly, a nylon net membrane with a regularly arranged pore as the matrix was coated with poly(pyrrole-3-carboxylic acid) via chemical vapor deposition (CVD) method. Then, poly(L-arginine) (PLA) as a highly specific ligand of bilirubin, was immobilized onto the surface of the composited membrane after the modification of heparin. Owing to the 3-dimensional molecular architecture of PLA, up to 86.1 % of bilirubin was efficiently cleared. Besides, the AAM exhibited effective anticoagulant activity in the measurement of clotting time, with suppressed thrombus formation, low hemolysis ratio, minimized platelet and leukocyte adhesion, and excellent biosafety. Therefore, the AAM has enormous potential in blood purification therapy for enhancing hemocompatibility and bilirubin removal.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111430DOI Listing
January 2021

Chitosan modified FeO/KGN self-assembled nanoprobes for osteochondral MR diagnose and regeneration.

Theranostics 2020 15;10(12):5565-5577. Epub 2020 Apr 15.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, PR China.

Chondral and osteochondral defects caused by trauma or pathological changes, commonly progress into total joint degradation, even resulting in disability. The cartilage restoration is a great challenge because of its avascularity and limited proliferative ability. Additionally, precise diagnosis using non-invasive detection techniques is challenging, which increases problems associated with chondral disease treatment. To achieve a theranostic goal, we used an integrated strategy that relies on exploiting a multifunctional nanoprobe based on chitosan-modified Fe3O4 nanoparticles, which spontaneously self-assemble with the oppositely charged small molecule growth factor, kartogenin (KGN). This nanoprobe was used to obtain distinctively brighter T-weighted magnetic resonance (MR) imaging, allowing its use as a positive contrast agent, and could be applied to obtain accurate diagnosis and osteochondral regeneration therapy. This nanoprobe was first investigated using adipose tissue-derived stem cells (ADSCs), and was found to be a novel positive contrast agent that also plays a significant role in stimulating ADSCs differentiation into chondrocytes. This self-assembled probe was not only biocompatible both and , contributing to cellular internalization, but was also used to successfully make distinction of normal/damaged tissue in T-weighted MR imaging. This novel combination was systematically shown to be biosafe via the decrement of apparent MR signals and elimination of ferroferric oxide over a 12-week regeneration period. Here, we established a novel method for osteochondral disease diagnosis and reconstruction. Using the FeO-CS/KGN nanoprobe, it is easy to distinguish the defect position, and it could act as a tool for dynamic observation as well as a stem cell-based therapy for directionally chondral differentiation.
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http://dx.doi.org/10.7150/thno.43569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196312PMC
May 2021

[email protected] mesenchymal stem cells as an "oxygen-laden guided-missile" for the enhanced photodynamic therapy on lung cancer.

Nanoscale 2020 Feb;12(5):3090-3102

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.

The critical issue in nanoscale medicine delivery systems is the targeted efficiency to guarantee the maximum accumulation of nanodrugs in tumors to exert better therapeutic action. In this study, we adopted an active and potent strategy based on mesenchymal stem cells (MSCs) certified with excellent tumor-tropism ability to load and ship [email protected] nanoparticles into a tumor site. Notably, under the premise of the negligible cellular toxicity of [email protected] on MSCs, its considerable uptake by MSCs enabled this nanoplatform ([email protected]) to distribute increasingly inside the tumor. Briefly, a Ce6 photosensitizer was bound to MnO2 nanospheres by physical adsorption, improving its own stability in blood circulation. Furthermore, the delivered [email protected] could modulate the tumor microenvironment (TME) by high sensitivity to excess hydrogen protons (H+) and H2O2. Thus, O2 generated by these reactions served as an abundant source for 1O2 conversion under a 633 nm laser exposure, which overcame the crucial bottleneck of the unfavorable hypoxia condition in TME for photodynamic therapy (PDT). In addition, MnO2 decomposed into Mn2+, which was represented by high T1 relaxivity in magnetic resonance imaging (MRI). The Mn2+ was finally removed rapidly from the body by liver metabolism and kidney filtration. These results endowed the original nanoplatform with striking potential for MSC-guided, Ce6-converted, MRI-monitored PDT for further innovation of a clinical cancer diagnosis-treatment agent.
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http://dx.doi.org/10.1039/c9nr07947eDOI Listing
February 2020

The vacuolization of macrophages induced by large amounts of inorganic nanoparticle uptake to enhance the immune response.

Nanoscale 2019 Dec 22;11(47):22849-22859. Epub 2019 Nov 22.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, P. R. China.

Inorganic nanoparticles (NPs), particularly iron oxide (IO) and gold (Au) NPs, are widely used in a variety of biomedical applications, such as diagnosis and cancer therapy. As an important component of host defense in organisms, macrophages play a crucial role in responding to foreign substances, such as nanoparticles. Thus, it is of utmost importance to understand the nanotoxicity effects on the immune system by investigating the influences of such nanoparticles. In this study, we found that macrophages can take up large amounts of amphiphilic polymer (PMA)-modified Au and IO NPs, which will induce macrophage cell vacuolization and enhance macrophage polarization. This mechanism is an essential part of the immune response in vivo. In addition, we report that smaller-sized nanoparticles (ca. 4 nm) show more significant effects on the macrophage polarization and caused lysosomal damage compared to larger nanoparticles (ca. 14 nm). Moreover, the amount of NP uptake in macrophages decreases upon trapping the PMA with PEG, resulting in reduced vacuolization and a reduced immune response. We hypothesize that vacuoles are formed in large amounts during NP uptake by macrophages, which enhances the immune response and induces macrophages toward M1 polarization. These findings are potentially useful for disease treatment and understanding the immune response when NPs are used in vitro and in vivo.
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http://dx.doi.org/10.1039/c9nr08261aDOI Listing
December 2019

Matrix metallopeptidase 2 targeted delivery of gold nanostars decorated with IR-780 iodide for dual-modal imaging and enhanced photothermal/photodynamic therapy.

Acta Biomater 2019 04 6;89:289-299. Epub 2019 Mar 6.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, PR China; National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China. Electronic address:

Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes ([email protected]/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that [email protected]/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, [email protected]/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of [email protected]/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. STATEMENT OF SIGNIFICANCE: We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of [email protected]/IR-780 promoted the prepared nanoparticles ([email protected]/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the [email protected]/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.
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http://dx.doi.org/10.1016/j.actbio.2019.03.008DOI Listing
April 2019

Gd-Ion-induced carbon-dots self-assembly aggregates loaded with a photosensitizer for enhanced fluorescence/MRI dual imaging and antitumor therapy.

Nanoscale 2018 Oct;10(40):19052-19063

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, P.R. China.

The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy. To reach the balance between an efficient accumulation in a tumor and rapid clearance from the body, herein we report a new multifunctional nanoprobe: photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots ([email protected]). The [email protected] were assembled from negatively-charged discrete C-dots using Gd3+ ions as a "glue". which also provided another function of in vivo nanoprobe monitoring via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic pH-dependent disassembly and drug-release property. Benefiting from these advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor-bearing mice under laser irradiation and gradual disassembly in the tumor for later body clearance. Therefore, the nanoprobe potentially provides a new strategy to solve the above balance issue, and brightens the future for antitumor monitoring and treatment.
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http://dx.doi.org/10.1039/c8nr05886eDOI Listing
October 2018

Ru-Catalyzed Asymmetric Hydrogenative/Transfer Hydrogenative Desymmetrization of Meso-Epoxy Diketones.

Org Lett 2016 06 23;18(11):2640-3. Epub 2016 May 23.

School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, P. R. China.

Via a strategy of asymmetric reductive desymmetrization, chiral cis-epoxy naphthoquinols with multiple contiguous stereocenters and functional groups were synthesized with excellent enantioselectivities (96-99% ee) and diastereoselectivities (8/1-15/1). A combined asymmetric hydrogenation/transfer hydrogenation mechanism was proposed based on experimental results.
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http://dx.doi.org/10.1021/acs.orglett.6b01073DOI Listing
June 2016
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