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.

Anlotinib是一种新型的小分子多靶酪氨酸激酶抑制剂，具有抑制血管生成和肿瘤生长的作用。迫切需要一个有效的靶向纳米递送系统，以有效地利用anlotinib来治疗黑色素瘤和肺转移。在这项研究中，开发了载有anlotinib的还原敏感纳米胶束，环状RGD肽（cRGDyk）-anlotinib还原敏感胶束（cARM），作为肿瘤微环境响应性递送平台。胶束载体通过还原敏感性两亲共聚物DSPE-SS-PEG2k和DSPE-PEG2k-cRGDyk的自组装形成。胶束两亲性嵌段中的二硫键对肿瘤细胞中GSH的升高有反应，以控制药物的释放。在B16F10荷瘤小鼠模型中，与非还原敏感性胶束相比，cRGDyk-anlotinib-RM（cARM）显示出更好的肿瘤组织积累和内在化。因此，这种降低敏感性的药物递送系统受益于其特异性，延长的血液循环时间，肿瘤细胞的有效吸收以及细胞内药物的快速释放，因此是一种有前途的策略。