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用于改善乳腺癌细胞凋亡活性及HER2靶向治疗的肿瘤归巢肽修饰的卡培他滨脂质体:研究

Tumor homing peptide modified liposomes of capecitabine for improved apoptotic activity and HER2 targeted therapy in breast cancer: studies.

作者信息

Singh Mantosh Kumar, Pindiprolu Sai Kiran S S, Reddy Sanapalli Bharat Kumar, Yele Vidyasrilekha, Ganesh G N K

机构信息

Department of Pharmaceutics, JSS College of Pharmacy, Ooty, JSS Academy of Higher Education & Research India

Department of Pharmacology, JSS College of Pharmacy, Ooty, JSS Academy of Higher Education & Research India.

出版信息

RSC Adv. 2019 Aug 12;9(43):24987-24994. doi: 10.1039/c9ra04814f. eCollection 2019 Aug 8.

Abstract

In the present study, we have formulated a liposomal formulation of cytotoxic agent capecitabine (CAP) to overcome its bioavailability issues. Then we have surface modified CAP loaded liposomes (CAP-LPs) with a tumour homing peptide (THP-CAP-LPs) to achieve site specific delivery to breast cancer cells. We found a significant cellular internalization of THP-CAP-LPs when compared to unmodified CAP-LPs. The cytotoxic effect of CAP was also significantly improved with THP-CAP-LPs by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by Western blot analysis. THP-CAP-LPs mediated delivery of CAP can be, therefore, a promising approach for improving antitumor activity and reducing off-target effects.

摘要

在本研究中,我们制备了细胞毒性药物卡培他滨(CAP)的脂质体制剂,以克服其生物利用度问题。然后,我们用肿瘤归巢肽对负载CAP的脂质体(CAP-LPs)进行了表面修饰(THP-CAP-LPs),以实现对乳腺癌细胞的位点特异性递送。我们发现,与未修饰的CAP-LPs相比,THP-CAP-LPs在细胞内的摄取显著增加。通过蛋白质免疫印迹分析观察到,THP-CAP-LPs还通过下调抗凋亡蛋白和上调促凋亡蛋白,显著提高了CAP的细胞毒性作用。因此,THP-CAP-LPs介导的CAP递送可能是一种改善抗肿瘤活性和减少脱靶效应的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468f/9070003/6fe57c4063c6/c9ra04814f-f1.jpg

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