Functional paclitaxel plus honokiol micelles destroying tumour metastasis in treatment of non-small-cell lung cancer

Abstract

Treatment effect of chemotherapy for aggressive non-small-cell lung cancer (NSCLC) is usually unsatisfactory for non-selective distributions of anticancer drugs, generation of vasculogenic mimicry (VM) channels, high metastasis and recurrence rate. Therefore, we developed a kind of dequalinium (DQA) modified paclitaxel plus honokiol micelles in this study to destroy VM channels and inhibit tumour metastasis. In vitro assays indicated that the targeting paclitaxel micelles with ideal physicochemical characteristics could exhibit not only the powerful cytotoxicity on Lewis lung tumour (LLT) cells but also the effective suppression on VM channels and tumour metastasis. Action mechanism studies manifested that DQA modified paclitaxel plus honokiol micelles could activate apoptotic enzymes caspase-3 and caspase-9 as well as down-regulate FAK, PI3K, MMP-2 and MMP-9. In vivo assays indicated that polymeric micelles could increase selective accumulation of chemotherapeutic drugs at tumour sites and showed a conspicuous antitumour efficacy. Hence, the DQA modified paclitaxel plus honokiol micelles prepared in this study provided a potential treatment strategy for NSCLC.