Abstract
Chemotherapy is a key medical method for cancer treatment because a large amount of patients are not suitable for surgeries, and the multi-drug resistance (MDR) and drug toxicity are still the major obstacles for clinical advancement. Here, we report the development of a nanoliposomal multi-drug delivery system with lapatinib and doxorubicin co-loaded in PEGylated nanoliposomes (Lip-LPT-DOX). Lip-LPT-DOX showed great chemosensitization of two human lung adenocarcinoma cell lines. LPT loaded in nanoliposomes could inhibit the function of ABC transporters, which could pump drugs out of cancer cells and lead to decreased intracellular drug accumulation. Lip-LPT-DOX showed a uniform size distribution and high loading efficiency with negligible drug leakage. Compared to clinical formulation, liposomal DOX (Lip-DOX), both intracellular DOX accumulation and therapeutic efficiency of Lip-LPT-DOX were significantly improved. Lip-LPT-DOX with half amount of DOX as Lip-DOX showed higher therapeutic efficiency, and it exhibited negligible toxicity to somatic cells, indicating the significantly reduced side effects. This novel nanoliposomal multi-drug delivery system provided a promising chemosensitization strategy that could likely overcome MDR and reduce the administration dose of DOX in cancer chemotherapy.
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