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脂质体介导的顺铂和紫杉醇的位点特异性递送:癌症化疗的有前途的方法。

Site-specific delivery of cisplatin and paclitaxel mediated by liposomes: A promising approach in cancer chemotherapy.

机构信息

Department of Thoracic Surgery, The first Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, PR China.

出版信息

Environ Res. 2023 Dec 1;238(Pt 1):117111. doi: 10.1016/j.envres.2023.117111. Epub 2023 Sep 19.

Abstract

The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.

摘要

药物的靶向递送,特别是抗癌药物,一直是研究人员感兴趣的领域,其原因在于细胞毒性药物在癌细胞中的积累量低。尽管联合癌症疗法在提高癌症药物敏感性方面具有益处,但药物的靶向递送似乎更为有效。在抗癌药物递送中,一种安全、生物相容且高效的纳米级递送系统是脂质体。它们的粒径较小,并且具有其他特性,如可调节的物理化学性质、易于功能化和高包封效率。顺铂是一种已在患者中获得临床批准的化疗药物,但由于缺乏靶向递送,其在癌细胞中的积累量较低,而且重复给药会导致耐药性的产生。顺铂/紫杉醇与基因和药物联合给药可提高肿瘤细胞的敏感性,但癌症治疗仍有进一步发展的空间。脂质体递送电化疗药物顺铂/紫杉醇可增加药物在肿瘤细胞中的积累,并破坏外排泵的活性,从而促进细胞毒性。此外,顺铂/紫杉醇递送联合光疗可以提高肿瘤抑制的潜力。包括 pH 敏感纳米颗粒在内的智能纳米颗粒可提供顺铂/紫杉醇的靶向递送。通过配体对脂质体进行功能化,可以提高其对肿瘤细胞的靶向性,从而介导顺铂/紫杉醇的靶向递送。最后,脂质体可以介导顺铂/紫杉醇与药物或基因的共递送,从而增强肿瘤抑制作用。由于药物耐药性导致癌症患者的治疗失败,而且顺铂/紫杉醇是常用的化疗药物之一,因此这些药物的递送可介导癌症的靶向抑制,防止耐药性的产生。由于脂质体的生物相容性和安全性,它们目前正在临床试验中用于癌症患者的治疗。在未来,应该在临床试验中确定使用脂质体的最佳剂量和在脂质体纳米载体上加载顺铂/紫杉醇的最佳浓度。

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