ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Yeneng Dai,Jinzhong Su,Kun Wu,Wenkang Ma,Bing Wang,Meixing Li,Pengfei Sun,Qingming Shen,Qi Wang,Quli Fan
Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG), and the antitumor drug, doxorubicin (DOX), were efficiently coencapsulated into the thermosensitive liposomes based on natural phase-change material. Folate and conjugated gadolinium (Gd) chelate-modified liposome shells enhance active targeting and magnetic resonance performance of the NPs while maintaining the size of the NPs. The ICG/DOX-loaded and gadolinium chelate conjugated temperature-sensitive liposome nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, and photodynamic therapy properties. With the coencapsulated ICG, DOX, and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided combination tumor therapy (chemotherapy, photothermotherapy, and photodynamic therapy). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging-guided NIR-triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.
研究领域:
癌症治疗
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纳米技术
·
生物医学工程
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药学
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医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gels
·
2022
·Vol. 8
·期 9
·570
·
IF 4.432
Qingrong Wu,Yu Fu,Wanying Yang,Shouxin Liu
Hydrogel is a good drug carrier, widely used in the sustained-release aspect of tumor drugs, which can achieve the continuous release of drugs to the tumor sites. In this study, diethylene glycol monomethyl ether methacrylate (MEO2MA) and poly (ethylene glycol) methyl ether methacrylate (OEGMA) are temperature-sensitive monomers. N-Methacryloyl-L-Histidine (Mist) is pH sensitive monomer and ligand for metal coordination bond. The temperature-sensitive monomers and pH sensitive monomer with stereocomplex of modified polylactic acid (HEMA-PLLA30/PDLA30) were mixed, under 2,2’-azobis (2-methylpropionitrile) (AIBN) as radical initiator, polymer was formed by free-radical polymerization. The polymer was then immersed in ZnSO4solution, the imidazole group of Mist monomer forms a tridentate metal coordination bond with Zn2+, temperature/pH double-responsive and physical double-crosslinked hydrogel was finally obtained. Comparing the hydrogen bond hydrogel, hydrogen bond and metal coordination bond double crosslinking hydrogel, metal coordination bond hydrogel, testing thermal stability, viscoelasticity, swelling, and morphology of three hydrogels. In addition, using UV-Visible spectroscopy (UV-Vis) to test the sustained release of the hydrophobic drug doxorubicin hydrochloride (DOX-HCl) in the human tumor environment (37 °C, pH = 5). We found that the temperature/pH double-responsive and physical double-crosslinked hydrogel had the most potential for the sustained drug release.
研究领域:
材料科学
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药学
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生物医学工程
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4 + and CD8 + T cells . Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
研究领域:
肿瘤学
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纳米技术
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免疫学
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药学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Long Xu,Mingying Zhao,Wenxia Gao,Yidi Yang,Jianfeng Zhang,Yuji Pu,Bin He
Thioketal and thioether are moieties used to fabricate reactive oxygen species (ROS)-responsive polymers for drug delivery. In this paper, three amphiphilic copolymers of mPEG-poly(ester-thioether), mPEG-poly(thioketal-ester) and mPEG-poly(thioketal-ester-thioether) were synthesized. The ROS-responsive behaviors of the three copolymers nanoparticles as drug carriers were investigated. The ROS-sensitivity was demonstrated by NMR, DLS, and SEM. mPEG-poly(ester-thioether) nanoparticles exhibited the fastest drug release rate, which possessed the best ROS sensitivity. The in vitro anticancer activity of the DOX-loaded nanoparticles was studied, the results revealed that the mPEG-poly(ester-thioether) nanoparticles showed the most efficient anticancer activity. Notably, all the three ROS-responsive copolymers nanoparticles showed enhanced cellular uptake and anticancer efficacy comparing to the control mPEG- b -PCL nanoparticles.
研究领域:
药学
·
纳米技术
·
癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2024
·
IF 5.5
Junfeng Ding,Tianran Wang,Yan Rong,Chaoliang He,Xuesi Chen
Comprehensive Summary Due to the immunosuppressive tumor microenvironment (TME), T cells are usually inactivated and tend to differentiate into regulatory T cells (Tregs) in the tumor tissues, which seriously hinders the anti-tumor efficiency of immunotherapy. In this study, an immune-stimulating polypeptide hydrogel conjugated with an indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl- D -tryptophan (D1MT), through a glutathione (GSH)-responsive spacer was developed as an immunotherapy platform capable of regulating the TME. A combined immunotherapy system was further constructed through encapsulating doxorubicin (Dox) and immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD-1) in the hydrogel. Dox released from the hydrogel could cause the immunogenic cell death (ICD) of tumor cells and induce the maturation of antigen presenting cells (APCs). After intratumoral injection, the multiple agent-loaded hydrogel elicited effective anti-tumor immunity in mice bearing B16F10 melanoma. Moreover, compared with the control hydrogel without D1MT, the immune-stimulating hydrogel showed better efficiency in improving the immunosuppressive TME with increased number of activated T cells and reduced number of Tregs. Therefore, the immune-stimulating hydrogel has great potential as a stimuli-responsive platform for regulating suppressive TME and enhanced anti-tumor chemo-immunotherapy.
研究领域:
癌症免疫疗法
·
药学
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生物医学工程
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Qingqing Yang,Yang Yang,Lian Li,Wei Sun,Xi Zhu,Yuan Huang
To improve the therapeutic efficacy of anticancer combination therapy, we designed a nanoplatform based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers that allows covalent bonding of two chemotherapeutics acting via different anticancer mechanisms and that can enter target cells by receptor-mediated endocytosis. Doxorubicin (DOX) was covalently conjugated to a nanosized HPMA copolymer using a pH-sensitive hydrazone bond and 5-fluorouracil (5-Fu) was conjugated to the same backbone using an enzymatically degradable oligopeptide Gly-Phe-Leu-Gly sequence. Then, the conjugate was decorated with galectin-3 targeting peptide G3-C12 [P-(G3-C12)-DOX-Fu]. The two drugs showed similar in vitro release profiles, suggesting that they may be able to work synergistically in the codelivery system. In galectin-3 overexpressed PC-3 human prostate carcinoma cells, P-(G3-C12)-DOX-Fu surprisingly exhibited comparable cytotoxicity to free DOX at high concentration by increasing cell internalization and exerting synergistic genotoxic effects of cell cycle arrest, caspase-3 activation, and DNA damage. In mice bearing PC-3 tumor xenografts, the use of tumor-targeting ligand substantially enhanced the intracellular delivery of P-(G3-C12)-DOX-Fu in tumors. The targeted dual drug-loaded conjugate inhibited tumor growth to a greater extent (tumor inhibition of 81.6%) than did nontargeted P-DOX-Fu (71.2%), P-DOX (63%), DOX·HCl (40.5%), P-Fu (32.0%), or 5-Fu (14.6%), without inducing any obvious side effects. These results demonstrate the potential of synergistic combination therapy using targeted nanocarriers for efficient treatment of prostate cancer.
研究领域:
纳米技术
·
药学
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肿瘤学
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Hui Qiao,Wenxia Zhang,Dongmei Zhang,Wenjun Yan,Jianguo Li,Yingqi Li
The redox homeostasis in tumor cells is an innate defense barrier for reactive oxygen species (ROS)-mediated tumor therapy. Herein, an intratumoral cascade-responsive multifunctional nanodiamond-based platform (NPCD) with a hydrodynamic diameter of 191 ± 5 nm triggering redox dyshomeostasis is fabricated by Cu2+-mediated coordination for polylysinated nanodiamond and doxorubicin (DOX) to achieve cancer-specific diagnosis and therapy. The NPCD nanoplatform enables precise tumor fluorescence localization and chemotherapy through a “turn on” effect due to being specifically activated by GSH to trigger DOX release at a low-pH tumor-specific environment instead of normal cells. Furthermore, NPCD realizes Cu+-based chemodynamic therapy (CDT) and induces GSH depletion by Cu2+ reduction to support CDT. These cause intracellular redox dyshomeostasis, making tumor cells more sensitive to the NPCD nanoparticles. Additionally, NPCD also possesses the intrinsic ability to reverse drug resistance. Of note, NPCD mainly accumulates in the tumor site in 4T1 tumor-bearing mice and enhances the efficacy of therapeutic interventions with negligible side effects. More interestingly, combined with programmed cell death ligand 1 antibody (anti-PD-L1) and imiquimod (R837), NPCD significantly suppresses distant tumor growth, indicating a good immune response. Therefore, this work opens perspectives for the further development of synergistic therapy through a Cu2+-mediated intratumoral cascade reaction.
研究领域:
纳米技术
·
癌症治疗
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氧化还原生物学
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药物递送系统
·
免疫肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Dengyue Chen,Jieli Yin,Chen Liu,Jiaqi Guo,Mao Li,Baoyin Chen,Xuewen Zhang,Bing Wang,Xuan Zhu
Both chemodynamic therapy and photodynamic therapy, based on the production of reactive oxygen (ROS), have excellent potential in cancer therapy. However, the abnormal redox homeostasis in tumor cells, especially the overexpressed glutathione (GSH) could scavenge ROS and reduce the anti-tumor efficiency. Therefore, it is essential to develop a simple and effective tumor-specific drug delivery system for modulating the tumor microenvironment (TME) and achieving synergistic therapy at the tumor site. In this study, self-assembled nanoparticles (named CDZP NPs) were developed by copper ion (Cu2+), Doxorubicin (Dox), Zinc phthalocyanine (ZnPc) and a trace amount of poly (2-(di-methylamino) ethylmethacrylate)-poly [(R)-3-hydroxybutyrate]-poly (2-(dimethylamino) ethylmethacrylate (PDMAEMA-PHB-PDMAEMA) through chelation, π-π stacking and hydrophobic interaction. This triple factors-responsive (pH, laser and GSH) nanoparticles demonstrated unique advantages through the synergistic effect. Highly controllable drug release ensured its effectiveness at the tumor site, Dox-induced chemotherapy and ZnPc-mediated fluorescence (FL) imaging exhibited the distribution of nanoparticles. Meanwhile, Cu2+-mediated GSH-consumption not only reduced the intracellular ROS elimination but also produced Cu+ to catalyze hydrogen peroxide (H2O2) and generated hydroxyl radical (∙OH), thereby enhancing chemodynamic and photodynamic therapy. Herein, this study provided a green and relatively simple method for preparing multifunctional nanoparticles that can effectively modulate the TME and improve synergetic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
肿瘤微环境
·
活性氧
·
协同治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Xiaoju Guo,Xiaoxiao Chen,Jiayi Ding,Feng Zhang,Shunyang Chen,Xin Hu,Shiji Fang,Lin Shen,Chenying Lu,Zhongwei Zhao,Jianfei Tu,Gaofeng Shu,Minjiang Chen,Jiansong Ji
Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO 3 by a CaCO 3 -assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2017
·
IF 4.162
Mei-Ling Chen,Shu-Chao Pang,Xue-Min Chen,Yi-Zhang,Lei Li
Developing a nanoscale drug delivery system with magnetic resonance imaging (MRI)/fluorescence imaging (FL) visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance has attracted great attentions in the area of nanomedicine . Herein, a novel permeable yolk-shell structured gadolinium-doped quantum dots nanocomposite was synthesized as a theranostic nanocarrier via an indirectly doping method. The as-prepared permeable nanoparticles with tunable color fluorescent emission, paramagnetic and accessible mesoporous channels could be developed as a novel nanomedical platform for integrated multimodal diagnosis and therapy. The hydrophilic nanocomposites exhibited tunable fluorescence as well as high longitudinal relaxivity (r 1 = 17.32 mM −1 s −1 ) in water with good colloidal stability. In vivo animal experiments further verified CSSP could achieve FL/MRI dual modality imaging. The widely used antineoplastic anthracycline drug doxorubicin (DOX) was absorbed into the permeable nanospheres with 95.3% loading efficiency and released in a pH-sensitive pattern. In vitro cancer cell cytotoxicity tests verified that the DOX-loaded nanocomposites had enhanced cytotoxicity compared with free DOX at the same concentration. The as-prepared nanocomposites present great potential as MRI/FL-visible nanoscale drug carrier to realize imaging-guided personalized therapy.
研究领域:
纳米医学
·
药物递送系统
·
分子成像
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）