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Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第2期13卷 879-896页

作者： Jianjun Cheng Haitian Zhao Bin Li Hua Zhang Qianyu Zhao Shiyao Fu Ying Han Weihong Lu Jiahua Shi Xin Yang School of Medicine and Health Harbin Institute of TechnologyHarbin 150001China Academician Workstation Jiangxi University of Chinese MedicineNanchang 330004China School of Chemistry and Chemical Engineering Harbin Institute of TechnologyHarbin 150001China Chongqing Research Institute Harbin Institute of TechnologyChongqing 401135China National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental NutrientsHarbin 150001China Key Laboratory of Natural Medicine and Immune-Engineering of Henan province Henan UniversityKaifeng 475004China

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer ***,developing multifunctional biodegradable,biocompatible,low-toxic but highly efficient,and clinically available transformed nano-immunostimulants remains a challenge and is in great ***,we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid(BA),a water-soluble chitosan oligosaccharide(COS),and a low toxic photosensitizer chlorin e6(Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer *** show that the designed nanodrugs harbored a smart and distinctive“dormancy”characteristic in chemotherapeutic effect with desired lower cytotoxicity,and multiple favorable therapeutic features including improved^(1)O_(2)generation induced by the reduced energy gap of Ce6,pH-responsiveness,good biodegradability,and biocompatibility,ensuring a highly efficient,synergistic ***,when combined with anti-PD-L1 therapy,both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy(PDT)could effectively activate antitumor immunity when treating primary or distant tumors,opening up potentially attractive possibilities for clinical immunotherapy.

关键词： Cancer immunotherapy Nano-immunostimulants Chemotherapeutic dormancy pro-drug Self-assembly Natural small molecule Betulinic acid Photodynamic therapy

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Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 35-52页

作者： Haijie Han Su Li Yueyang Zhong Yue Huang Kai Wang Qiao Jin Jian Ji Ke Yao Eye Center the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Zhejiang provincial Key Lab of Ophthalmology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.

关键词： Gemcitabine pro-drug Nano-drug Cancer therapy

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Inhibition of human gastric carcinoma cell growth by atofluding derivative N_3-o-toluyl-fluorouracil

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World Journal of Gastroenterology 2006年第42期12卷 6766-6770页

作者： Jian Liu Wen-Fang Xu Shu-Xiang Cui Yong Zhou Yun-Xia Yuan Ming-Hui Chen Ruo-Han Wang Ruo-Yan Gai Masatoshi Makuuchi Wei Tang Xian-Jun Qu Department of Pharmacology School of Pharmaceutical Sciences Shandong University Jinan 250012 Shandong Province China Department of Pharmacy Second Affiliated Hospital Shandong Traditional Chinese Medical University Jinan 250001 Shandong Province China Department of Pharmacology The Institute of Materia Medica Shandong Academy of Medical Sciences Jinan 250062 Shandong Province China Center for drug Evvaluation and Certification of Shandong Jinan 250014 Shandong Province China Hepato-Biliary-Pancreatic Surgery Division Department of Surgery Graduate School of Medicine The University of Tokyo 113-8655 Tokyo Japan

AIM： To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil （TFU） on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS： Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS： TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In v/vo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION： TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil （5-FU） mediated by the enzymes.

关键词： N3-o-toluyl-fluorouracil Gastric carcinoma cells pro-drug Growth inhibition

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