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  • Title: Lipopepsomes: A novel and robust family of nano-vesicles capable of highly efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride in vivo.
    Author: Qiu M, Sun H, Meng F, Cheng R, Zhang J, Deng C, Zhong Z.
    Journal: J Control Release; 2018 Feb 28; 272():107-113. PubMed ID: 29355618.
    Abstract:
    Doxil® is the first FDA-approved anti-cancer nano-drug. Notably, no targeted liposomal formulation has advanced to clinical stage despite tremendous work undertaken, partly due to a low stability of liposomes. Here, we report on novel lipopepsomes self-assembled from poly(ethylene glycol)-b-poly(α-aminopalmitic acid) as a stable and versatile alternative to liposomes for highly efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride (Dox·HCl). Interestingly, lipopepsomes could be easily decorated with 20mol% cRGD peptide and loaded with 17.4wt% Dox·HCl, giving cRGD-LPP-Dox with a small size of ~80nm. cRGD-LPP-Dox exhibited a high stability against 10% FBS and restrained drug release under physiological conditions. Flow cytometry, confocal microscopy and MTT assays using αvβ3-overexpressing A549 tumor cells showed obviously more efficient uptake and higher anticancer activity for cRGD-LPP-Dox than for non-targeted LPP-Dox and clinically used liposomal Dox (Lipo-Dox) controls. Notably, cRGD-LPP-Dox exhibited markedly enhanced toleration and tumor accumulation than Lipo-Dox. The therapeutic studies demonstrated that cRGD-LPP-Dox achieved effective suppression of orthotopic A549 human lung tumor in nude mice, resulting in significantly improved survival rate as compared to LPP-Dox and Lipo-Dox groups. Lipopepsomes with small size, efficient loading of Dox·HCl, high stability and versatile ligand decoration have appeared as a highly attractive nanoplatform for targeted tumor chemotherapy.
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