Construction and antitumor effects of antitumor micelles with cyclic RGD-modified anlotinib

• DOI: 10.1016/j.nano.2020.102224
• Publication Date: 2020-05-17T02:03:43Z
• Authors: Yan Zhang; Hui Chen; Nannan Feng; Xiangying Xin; Yue Xu; Pengchao Huo; Xuesong Wang; Nan Zhang
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Wound Healing; Indoles; Blotting, Western; Melanoma, Experimental; Peptides, Cyclic; 3. Good health; Mice; 03 medical and health sciences; Cell Line, Tumor; Quinolines; Animals; Humans; Melanoma; Micelles; Cell Proliferation

Anlotinib is a new type of small-molecule multi-target tyrosine kinase inhibitor with inhibitory effects against angiogenesis and tumor growth. An effective targeted nano-delivery system is urgently needed to effectively utilize anlotinib for the treatment of melanoma and lung metastases. In this study, an anlotinib-loaded reduction-sensitive nanomicelle, cyclic RGD peptide (cRGDyk)-anlotinib-reduction sensitive micelles (cARM), was developed as a tumor microenvironment-responsive delivery platform. The micelle carrier was formed by the self-assembly of reduction-sensitive amphiphilic copolymers DSPE-SS-PEG2k and DSPE-PEG2k-cRGDyk. The disulfide bonds in the amphiphilic block of micelles are responsive to elevated GSH in tumor cells for controlled drug release. In a B16F10 tumor-bearing mouse model, cRGDyk-anlotinib-RM (cARM) showed better tumor tissue accumulation and internalization than those for non-reduction-sensitive micelles. Therefore, this reduction-sensitive drug delivery system benefits from its specificity, prolonged blood circulation time, effective absorption by tumor cells, and rapid release of intracellular drugs and is therefore a promising strategy.