<br>β-糖苷酶敏感口服纳米颗粒用于结直肠癌的光热和化疗联合治疗,Journal of Materials Chemistry B

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β-糖苷酶敏感口服纳米颗粒用于结直肠癌的光热和化疗联合治疗
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2024-01-19 , DOI: 10.1039/d3tb02393a
Jingning Zhou ₁ , Zequn Zhuang ₁ , Rui Gao ₂ , Ran Li ₃ , Yigang Chen ₁

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结直肠癌是世界上最常见的恶性肿瘤之一，其治疗策略主要包括手术切除、化疗、辅助放疗和免疫治疗。其中，化疗由于缺乏肿瘤靶向性，不可避免地产生全身毒性，且长期用药引起的耐药性时常发生，极大地制约了单纯化疗的疗效。为了解决上述问题，采用鼠李糖脂封装化疗药物5-FU和光热剂铋纳米片（BiNS），以壳聚糖作为纳米粒子的壳，BiNS@RHL-CS/5-FU NPs口服给药制剂已成功制备。当在胃和小肠中运输时，鼠李糖脂和壳聚糖壳的双重保护阻止了BiNS和5-FU的早期释放。当转运至结肠时，微环境中存在的β-糖苷酶随着pH的升高而降解壳聚糖外壳，粒径的减小有利于肿瘤组织摄取纳米颗粒，从而大大提高了5-FU的肿瘤靶向能力，并减少了全身毒性。由于BiNS的存在，1.0 W cm ^-2 808 nm激光照射显着升高肿瘤部位的温度，不仅直接杀死肿瘤细胞，而且促进肿瘤组织中纳米粒子的细胞摄取和渗透，加速释放5 -FU并提高肿瘤细胞对化疗的敏感性，最终解决传统单纯化疗的缺点。在体外和体内实验中均取得了优异的抗肿瘤功效。

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β-Glycosidase sensitive oral nanoparticles for combined photothermal and chemo treatment of colorectal cancer

Colorectal cancer is one of the most common malignant tumors in the world, and its treatment strategies mainly include surgical resection, chemotherapy, adjuvant radiotherapy, and immunotherapy. Among them, chemotherapy inevitably produces systemic toxicity due to the lack of tumor targeting properties and drug resistance caused by long-term medication frequently occurs, immensely constraining the efficacy of chemotherapy alone. To solve the above-mentioned problems, rhamnolipid was used to encapsulate the chemotherapeutic drug 5-FU and photothermal agent bismuthene nanosheets (BiNS), chitosan was applied as the shell of the nanoparticle, and BiNS@RHL-CS/5-FU NPs for oral administration was successfully prepared. When transported in the stomach and small intestine, the double protection of rhamnolipid and chitosan shell prevented the early release of BiNS and 5-FU. When transported to the colon, β-glycosidase existing in the microenvironment along with elevated pH degraded the chitosan shell, and the reduction in particle size was beneficial for tumor tissue to uptake nanoparticles, thus greatly improving the tumor targeting ability of 5-FU and reducing the systemic toxicity. Due to the presence of BiNS, 1.0 W cm⁻² 808 nm laser irradiation significantly increased the temperature of the tumor site, not only killing tumor cells directly but also promoting cell uptake and penetration of nanoparticles in the tumor tissue, accelerating the release of 5-FU and improving the sensitivity of tumor cells to chemotherapy, eventually solving the shortcomings of traditional chemotherapy alone. Excellent anti-tumor efficacy has been achieved in both in vitro and in vivo experiments.

更新日期：2024-01-19

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