Stimulus-responsive nanosystem is a powerful method to improve the bioavailability and reduce the side effects of anticancer agents. In the present study, a customized dual pH-responsive micellar nanoplatform (DOX+LAP-M) based on polycarbonate-doxorubicin conjugate micelles was prepared to co-deliver the chemotherapeutic agent lapatinib for inhibiting tumor growth and metastasis. DOX+LAP-M micelles with spherical morphology had a size of ~112 nm and had an initial negative surface charge, which are favorable characteristics for long-term circulation in the blood. Once the micelles accumulated in tumor tissues, the intrinsic tumor extracellular acidity triggered the charge switch of DOX+LAP-M micelles from -1 to 9 mV, thereby facilitating cell internalization and tumor penetration. Subsequently, the pH-sensitive micellar core accelerated the release of doxorubicin and lapatinib in the acidic intracellular environment. DOX+LAP-M micelles effectively inhibited the proliferation, migration, and invasion of 4T1 cells in vitro; furthermore, the administration of DOX+LAP-M micelles in 4T1 xenograft-bearing mice suppressed solid tumor growth with an inhibitory rate of 90.2% and significantly decreased pulmonary metastatic nodules, without significant systemic toxicity. This multifunctional micellar system has high potential for clinical cancer therapy.

刺激响应的纳米系统是提高生物利用度并减少抗癌药副作用的有效方法。在本研究中，基于聚碳酸酯-阿霉素共轭胶束的定制的双重pH响应胶束纳米平台（DOX + LAP-M）被制备来共同递送化学治疗剂拉帕替尼以抑制肿瘤的生长和转移。具有球形形态的DOX + LAP-M胶束的尺寸约为112 nm，并具有初始的负表面电荷，这对血液在血液中的长期循环是有利的。一旦胶束在肿瘤组织中积累，内在的肿瘤细胞外酸度就会将DOX + LAP-M胶束的电荷开关从-1转移到9 mV，从而促进细胞内在化和肿瘤渗透。后来，pH敏感的胶束核心在酸性细胞内环境中加速了阿霉素和拉帕替尼的释放。DOX + LAP-M胶束有效抑制4T1细胞的增殖，迁移和侵袭体外; 此外，在携带4T1异种移植物的小鼠中施用DOX + LAP-M胶束抑制了实体瘤的生长，抑制率为90.2％，并显着降低了肺转移性结节，而没有明显的全身毒性。这种多功能的胶束系统在临床癌症治疗中具有很高的潜力。