National Engineering Research Center for Nanomedicine

Wuhan, China

National Engineering Research Center for Nanomedicine

Wuhan, China
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Kong M.,Huazhong University of Science and Technology | Kong M.,Sanmenxia Central Hospital | Tang J.,China Three Gorges University | Qiao Q.,Huazhong University of Science and Technology | And 7 more authors.
Theranostics | Year: 2017

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-β and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-ß. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect. © Ivyspring International Publisher.


Li G.,National Engineering Research Center for Nanomedicine | Li G.,Huazhong University of Science and Technology | Zhang Z.,National Engineering Research Center for Nanomedicine | Zhang Z.,Huazhong University of Science and Technology
Journal of Controlled Release | Year: 2016

Nanoimmunotherapy, the application of nanotechnology for sustained and targeted delivery of antigens to dendritic cells (DCs), has attracted much attention in stimulating antigen-specific immune response for antitumor therapy. In order to in situ deliver antigens to DCs for efficient antigen presentation and subsequent induction of strong cytotoxic T lymphocytes (CTL) response, here we developed a multi-peptide (TRP2180-188 and HGP10025-33) and toll-like receptor 4 agonist (monophosphoryl lipid A) codelivery system based on lipid-coated zinc phosphate hybrid nanoparticles (LZnP NPs). This delivery system equips with the chelating property of zinc to realize the high encapsulation efficiency with antigenic peptides and the influence on immune system with adjuvant-like feature. The combination of H-2Kb and H-2Db-restricted peptides could provide multiple epitopes as the target of specific MHC alleles, making tumor more difficult to escape from the surveillance of immune system. The formulated LZnP nano-vaccine with the size of 30 nm and outer leaflet lipid exhibited antitumor immunity as the secretion of cytokines in vitro and increased CD8+ T cell response from IFN-γ ELISPOT analysis ex vivo. The antitumor effects were further evidenced from the prophylactic, therapeutic and metastatic melanoma tumor models compared with free antigens and single peptide-loaded nano-vaccines. These results validate the benefit of LZnP-based vaccine for antitumor immunity and indicate that co-delivery of tumor antigens along with adjuvant may be an optimized strategy for tumor immunotherapy. © 2016, Elsevier B.V. All rights reserved.


Bao Y.,Tongji Hospital | Zhang Z.,National Engineering Research Center for Nanomedicine | Zhang Z.,Huazhong University of Science and Technology
Journal of Controlled Release | Year: 2017

Cancer is still the leading cause of death. While traditional treatments such as surgery, chemotherapy and radiotherapy play dominating roles, recent breakthroughs in cancer immunotherapy indicate that the influence of immune system on cancer development is virtually beyond our expectation. Manipulating the immune system to fight against cancer has been thriving in recent years. Further understanding of tumor anatomy provides opportunities to put a brake on immunosuppression by overcoming tumor intrinsic resistance or modulating tumor microenvironment. Nanotechnology which provides versatile engineered approaches to enhance therapeutic effects may potentially contribute to the development of future cancer treatment modality. In this review, we will focus on the application of nanotechnology both in boosting anti-tumor immunity and collapsing tumor defense. © 2017


Zhou Q.,National Engineering Research Center for Nanomedicine | Mu K.,Huazhong University of Science and Technology | Jiang L.,National Engineering Research Center for Nanomedicine | Xie H.,China Patent Information Center | And 8 more authors.
International Journal of Nanomedicine | Year: 2015

Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r2) of micelles was 215.4 mM-1⋅s-1, with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation. © 2015 Zhou et al.


Xiong W.,Huazhong University of Science and Technology | Xiong W.,National Engineering Research Center for Nanomedicine | Wang W.,National Engineering Research Center for Nanomedicine | Wang Y.,National Engineering Research Center for Nanomedicine | And 7 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2011

In this paper, a dual temperature/pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogel (PNA) was prepared and utilized as a drug carrier. The anti-cancer drug doxorubicin (DOX) was covalent bound to PNA via an acid-labile hydrazone linkage. DOX-PNA conjugates had a pH-dependent LCST, which was 41 °C and 43 °C at pH 5.3 and 6.8 respectively, but higher than 50 °C at pH 7.4. The nanogels which were hydrophilic below LCST and changed to hydrophobic state above LCST possessed dual pH/temperature dependent cellular uptake and cytotoxicity. With increasing temperature, the cellular uptake of DOX-PNA was almost no difference at pH 7.4, but enhanced about 43% at pH 6.8. So the cytotoxicity of DOX-PNA also increased in higher temperature and lower pH value. It was able to distinguish tumor extracellular pH from physiological pH under hyperthermia of 43 °C, suggesting a great potential for anti-cancer therapy. © 2011 Elsevier B.V.


Yang H.,National Engineering Research Center for Nanomedicine | Wang Q.,Huazhong University of Science and Technology | Chen W.,National Engineering Research Center for Nanomedicine | Zhao Y.,National Engineering Research Center for Nanomedicine | And 4 more authors.
Molecular Pharmaceutics | Year: 2015

Long circulation in the blood, efficient cellular internalization, and intracellular drug release in the tumor cells are major challenges in the development of ideal anticancer drug delivery systems. In this paper, hydrophilicity/hydrophobicity reversable and redox-sensitive poly(oligo(ethylene glycol) methacrylates-ss-acrylic acid) (P(OEGMAs-ss-AA)) nanogels were constructed as drug carriers for cancer therapy. The nanogels underwent a pH-dependent hydrophilic/hydrophobic change. The nanogels were hydrophilic under physiological conditions (pH 7.4, 37 °C), resulting in fewer opsonization of proteins and less phagocytosis by macrophage RAW264.7 cells, while they were hydrophobic in the tumor tissues (pH 6.5, 37 °C), resulting in strong internalization by Bel7402 cells. The doxorubicin (DOX) release from DOX-loaded nanogels was increased in intracellular reductive and lysosome acidic environments. DOX-loaded nanogels exhibited higher cellular proliferation inhibition to GSH-OEt-pretreated Bel7402 cells at pH 6.5 than to unpretreated cells at pH 7.4. Further studies showed that the loaded DOX and nanogels were internalized into the cells together via both lipid raft/caveolae- and clathrin-mediated endocytic pathways. After internalization, the DOX-loaded nanogels were transported via the specific route in endo/lysosomal system. The loaded DOX was released from the nanogels with the introduction of intracellular GSH and entered the nucleus. This study indicated that the hydrophilicity/hydrophobicity reversable and redox-sensitive nanogels might be used as potential carriers for anticancer drugs, which provided a foundation for designing an effective drug delivery system for cancer therapy. © 2015 American Chemical Society.


Chen H.,Huazhong University of Science and Technology | Chen H.,National Engineering Research Center for Nanomedicine | Zhu H.,Huazhong University of Science and Technology | Zhu H.,National Engineering Research Center for Nanomedicine | And 12 more authors.
ACS Nano | Year: 2011

Assembly of nanoparticles as interfacial stabilizers at oil-in-water (O/W) interfaces into microscopic suprastructures for stabilizing Pickering emulsions is an intriguing focus in the fields of chemical industry and material sciences. However, it is still a major challenge to assemble nanoscale suprastructures using nanoparticles as building blocks at O/W interfaces for fabricating nanoscale emulsion droplets with applicable potential in nanomedicine. Here, we show that it is possible to fabricate the nanodroplets by assembling highly deformable nanogels into the nanoscale suprastructures at spatially confined O/W interfaces. The compressed assembly of the nanogels induced the formation of the nanoscale suprastructures upon energy input at the nanoscale O/W interface. The hydrogen bonding interaction between the nanogels at the O/W interface are possibly responsible for the stabilization of the nanoscale suprastructures. The nanoscale suprastructures are further employed to stabilize the paclitaxel-loaded nanodroplets, which are found to provide sustained release of the drug, enhanced in vitro cytotoxicity, and prolonged in vivo blood circulation. Furthermore, the tissue distribution and antitumor efficacy studies show that the nanodroplets could induce a higher drug accumulation at the tumor site and enhance tumor growth inhibition when compared with the commercial product. This approach provides a novel universal strategy to fabricate nanoscale suprastructures for stabilizing nanodroplets with built-in payloads using deformable nanoparticles and displays a promising potential in nanomedicine. © 2011 American Chemical Society.

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