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Synthesis of a reduction-sensitive Bletilla striata polysaccharide amphiphilic copolymer

Chinese Chemical Letters 2018年第6期29卷 831-833页

作者： Dandan Sun Miao Wang Danyang Ji Jin Qiao Tong He Xin Liu Qingxiang Guan School of Pharmacy Jilin University

Recently, much special attention has been focused on the development of amphiphilic copolymers.Herein, a reduction-sensitive stearic acid grafted-Bletilla striata polysaccharide copolymer（BSP-ss-SA）was synthesized and characterized. BSP-ss-SA copolymer could spontaneously form micelles with an average particle size of（106 ？ 4.36） nm. Particle sizes were dramatically larger under 10 mmol/L dithiothreitol（DTT） than that in absence of 10 mmol/L DTT. Docetaxel loading content and encapsulation efficiency of micelles were 5.94 wt% and 72.75 wt%, respectively. The docetaxel release rate in vitro in micelles could be remarkably accelerated in pH 7.4 phosphate buffer solution（PBS） containing 10 mmol/L DTT compared with that of micelles（0 mmol/L DTT）. Furthermore, MTT results demonstrated the anticancer activities in vitro of docetaxel-loaded BSP-ss-SA micelles on HepG2 were superior to that of docetaxel injection. BSP-ss-SA copolymer might be a promising nanocarrier for cancer chemotherapy drugs.

关键词： Bletilla striata Amphiphilic polymer Micelle reduction sensitivity Anticancer activity

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Stimuli-responsive Nanoparticles for the Efficient Co-delivery of Chemotherapeutic Agents Doxorubicin and siPD-L1 to enhance the anti-tumor effect

Stimuli-responsive Nanoparticles for the Efficient Co-delive...

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2018年第十二届中国药物制剂大会

作者：周烨娟张学农苏州大学药学院

In this work, we designed dual pH/reduction sensitive nanoparticles, which were composed of polyL-lysine-lipoic acid（PLL-LA） as a reduction-responsive core, and modified with a tumor extracellular pH（pHe） triggered detachable PEG layer（sPEG） for the efficient co-delivery of doxorubicin（DOX） and PD-L1 siRNA（siPD-L1）. Under the physiological condition, the PEG layer was stable and led to prolonged circulation time. After accumulated in tumor sites, pHe-sensitive linkage between PEG layer and NPs degraded, which enhanced the internalization of NPs by tumor cells. Then, the high-concentration glutathione（GSH） within tumor cells triggered the destabilization of DOX-siPD-L1/sPEG-PLL-LA NPs, followed by rapid release of payloads DOX and siPD-L1 which diffused to nuclei and siPD-L1 in cytoplasm, respectively. Compared with that at p H 7.4, s PEG-PLL-LA NPs exhibited a higher cellular uptake and improved cytotoxicity against B16 cells in vitro at pH 6.5. Moreover, the sPEG NPs showed good tumor-targeting ability and excellent tumor-penetrating efficacy in tumor tissues. In conclusion, the sPEG modified NPs provided great potentials in cancer treatment.

关键词： PEGylation tumor acidity reduction sensitivity siRNA chemotherapy immunity therapy

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