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| 1 | GSH-sensitive polymeric prodrug: Synthesis and loading with photosensitizers as nanoscale chemo-photodynamic anti-cancer nanomedicine显示文摘Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug(molecular weight,MW: 93.5 k Da) was produced by reversible addition-fragmentation chain transfer(RAFT) polymerization. The amphiphilic block polymer-doxorubicin(DOX) prodrug was employed to deliver a hydrophobic photosensitizer(PS), chlorin e6(Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione(GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 k Da in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4 T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition(TGI,58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent. | Lei Luo Yiming Qi Hong Zhong Shinan Jiang Hu Zhang Hao Cai Yahui Wu Zhongwei Gu Qiyong Gong Kui Luo | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 3 |
| 2 | Design, preparation and pharmacodynamics of ICG-Fe(Ⅲ) based HCPT nanocrystals against cancer显示文摘The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry.However,the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin,which have potential toxicity risks including hemolysis and allergies.Here,we designed an amorphous nanocrystal drug complex(IHNC),which is stabilizer-free and composed of indocyanine green(ICG)framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin(HCPT).Considering the possibility of industrial manufacturing,IHNC was simply prepared with the assistance of ferric ion(III)via supramolecular assembly strategy.The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III)framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio.The IHNC was stable at physiological pH,with excellent PTT/PDT efficacy,and in vivo probing characteristics.The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo.Moreover,such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%.These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy. | Qiongzhe Ren Xuefeng Tang Yi Lu Qing Li Zhiqian Liao Shinan Jiang Haoli Zhang Zhigang Xu Lei Luo | 2022 | Asian Journal of Pharmaceutical Sciences2022，17，4： | 0 |
| 3 | Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway显示文摘Acute lung injury(ALI)is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers,resulting in high incidence and mortality rates.Currently,there is a lack of safe and effective drugs for the treatment of ALI.In a previous clinical study,we observed that Jinyinqingre oral liquid(JYQR),a Traditional Chinese Medicine formulation prepared by the Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings.However,the potential role of JYQR in ALI/acute respiratory distress syndrome(ARDS)and its anti-inflammatory mechanism remains unexplored.Thus,the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide(LPS)-induced ALI and an in vitro RAW264.7 cell model.JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues.Additionally,JYQR administration led to a noteworthy reduction in total protein levels within the BALF,a decrease in MPAP,and attenuation of pleural thickness.These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI.Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins,namely NLRP3 and GSDMD,as well as proinflammatory cytokine levels in mice and RAW2647 cells.Consequently,JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway.JYQR exerts a protective effect against LPS-induced ALI in mice,and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway. | WANG Shuhui LEI Pan FENG Ying JIANG Mingzhu LIU Zegan SHEN Ting MA Shinan WANG Libo GUO Xingrong DU Shiming 无 | 2023 | Chinese Journal of Natural Medicines2023，21，6： | 0 |
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