Singh Mantosh Kumar, Pindiprolu Sai Kiran S S, Reddy Sanapalli Bharat Kumar, Yele Vidyasrilekha, Ganesh G N K
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.
RSC Adv. 2019 Aug 12;9(43):24987-24994. doi: 10.1039/c9ra04814f. eCollection 2019 Aug 8.
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.
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。