To achieve redox-controlled and tumor active targeting synergistic self-delivery of camptothecin and gemcitabine, redox-sensitive rod-shaped nano-micelles are fabricated through co-assembling between camptothecin-disulfide bond-PEG₂₀₀₀-4-carboxyphenylboronic acid and camptothecin-disulfide bond-gemcitabine conjugate. Most of all, for multidrug resistant cancer cell line MCF-7/ADR which is more resistant against CPT, increasing content of CPT in the formulation is favorable for synergistic effect of CPT and GEM drug combination. Benefiting from simple co-assembling strategy, it is easy and convenient to adjust drug ratio of CPT/GEM to optimize the synergism of drug combination. In addition, nano-micelles fabricated from co-assembling are endowed with both high absolute drug concentration and enhanced colloidal stability, which is helpful to in vivo studies. Transmission electron microscopy observation confirmed the rod-shaped morphology, which is beneficial to cellular internalization, of co-assembled nano-micelles resulting from π-π stacking interactions of CPT moieties and appropriate hydrophilic and hydrophobic interactions during co-assembling. Taking advantages of the specific interactions between 4-carboxyphenylboronic acid and sialic acid, co-assembled nano-micelles exerted enhanced cellular internalization. Noteworthy, compared with cocktail mixture of free CPT and GEM, nano-micelles greatly alleviated drug reflux against MCF-7/ADR and 4T1 cells. The nano-micelles realized redox-controlled ratio-metric and synchronous delivery of CPT and GEM, thereby pronounced in vitro synergistic antiproliferative effect against MCF-7/ADR and 4T1cells. Furthermore, in vivo bio-distribution analysis indicated the preferential accumulation of nano-micelles at tumor site, which could increase therapeutic efficacy and decrease side effects of non-selective anticancer drugs. Taken together, the redox-sensitive CPBA decorated co-assembled nano-micelles provided a promising strategy for tumor active targeting and redox-controlled intracellular synergistic combinational delivery of chemotherapeutics.

为了实现喜树碱和吉西他滨的氧化还原控制和肿瘤活性靶向协同自传递，通过喜树碱-二硫键-PEG _2000的共组装制备了氧化还原敏感的棒状纳米胶束。-4-羧苯基硼酸和喜树碱-二硫键-吉西他滨偶联物。最重要的是，对于对CPT更具抵抗力的多药耐药癌细胞系MCF-7 / ADR，制剂中CPT含量的增加有利于CPT和GEM药物组合的协同作用。得益于简单的协同装配策略，调整CPT / GEM的药物比例以优化药物组合的协同作用非常容易。另外，通过共组装制备的纳米胶束具有很高的绝对药物浓度和增强的胶体稳定性，这对体内有帮助学习。透射电子显微镜观察证实了由CPT部分的π-π堆叠相互作用以及在共组装期间适当的亲水和疏水相互作用产生的共组装的纳米胶束的棒状形态，这对细胞内化是有益的。利用4-羧基苯基硼酸和唾液酸之间的特异性相互作用，共组装的纳米胶束发挥了增强的细胞内在化作用。值得注意的是，与游离CPT和GEM的混合物相比，纳米胶束大大减轻了针对MCF-7 / ADR和4T1细胞的药物逆流。纳米胶束实现了CPT和GEM的氧化还原控制比例测量和同步传送，从而在体外显着对MCF-7 / ADR和4T1细胞具有协同抗增殖作用。此外，体内生物分布分析表明纳米胶束优先聚集在肿瘤部位，这可以提高治疗效果并降低非选择性抗癌药的副作用。总之，氧化还原敏感的CPBA装饰的共组装纳米胶束为肿瘤活性靶向和氧化还原控制的细胞内协同化学疗法的联合递送提供了有希望的策略。