The effective accumulation at tumor sites and endocytosis by tumor cells for anticancer agents in carriers are essential in successful cancer therapy, and both of the processes are affected by the surface charge of drug carriers. In this study, vitamin C (VC) was employed as an "exogenous switch" to trigger the surface charge conversion of DOX-loaded micelles to obtain a better antitumor effect. T micelles formed by poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-PDEA-ss-PMPC) turned their ζ potentials from +1 mV to +18 mV under treatment of 20 mM VC, while the ζ potentials of control R micelles formed by PCL-ss-P(DEA-r-MPC) almost remained unchanged under the same condition. DOX-loaded T@DOX and R@DOX had high DLCs of 12% and 13.8%, respectively, and both showed an accelerated drug release in a reductive environment (10 mM GSH or 20 mM VC) at pH 5.0. Notably, due to the surface charge conversion and fast drug release triggered by VC, T@DOX/VC (T@DOX was pretreated by VC) showed an enhanced cytotoxicity and cellular uptake superior to T@DOX, R@DOX, and R@DOX/VC. T@DOX/VC also displayed the in vivo antitumor effect well, which was comparable to DOX·HCl but with less toxic side effects than DOX·HCl. In summary, VC as an exogenous trigger can induce a better antitumor effect of drug-loaded micelles with a suitable polymer structure by charge conversion, and T@DOX/VC has shown to be as a promising approach to achieve potent treatment of tumors.

中文翻译：

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pH /还原反应性胶束的外源维生素C引发的表面电荷转化，可提高负载的阿霉素的肿瘤特异性活性。

载体中抗癌剂在肿瘤部位的有效积累和肿瘤细胞的内吞作用对于成功的癌症治疗至关重要，并且这两个过程都受到药物载体表面电荷的影响。在这项研究中，维生素C（VC）被用作“外源转换”来触发DOX负载胶束的表面电荷转化，以获得更好的抗肿瘤作用。聚（ε-己内酯）-b-聚（甲基丙烯酸N，N-二乙基氨基乙基酯）-ss-b-聚（2-甲基丙烯酰氧基乙基磷酰胆碱）（PCL-PDEA-ss-PMPC）形成的T胶束的ζ电位从+1在20 mM VC处理下，mV至+18 mV，而由PCL-ss-P（DEA-r-MPC）形成的对照R胶束的ζ电位在相同条件下几乎保持不变。加载DOX的T @ DOX和R @ DOX的DLC分别为12％和13.8％，在还原性环境（10 mM GSH或20 mM VC）和pH 5.0下，二者均显示出加速的药物释放。值得注意的是，由于VC引发的表面电荷转换和快速药物释放，T @ DOX / VC（用VC预处理T @ DOX）显示出优于T @ DOX，R @ DOX和R @的增强的细胞毒性和细胞摄取DOX / VC。T @ DOX / VC还具有很好的体内抗肿瘤作用，与DOX·HCl相当，但毒性副作用比DOX·HCl少。总而言之，VC作为外源性触发剂，可以通过电荷转换诱导具有适当聚合物结构的载药胶束更好的抗肿瘤作用，而T @ DOX / VC已被证明是实现有效治疗肿瘤的一种有前途的方法。由于VC触发的表面电荷转换和快速药物释放，T @ DOX / VC（T @ DOX经过VC预处理）显示出优于T @ DOX，R @ DOX和R @ DOX /的增强的细胞毒性和细胞摄取/ VC。T @ DOX / VC还具有良好的体内抗肿瘤作用，与DOX·HCl相当，但毒性副作用比DOX·HCl少。总而言之，VC作为外源性触发剂，可以通过电荷转换诱导具有适当聚合物结构的载药胶束更好的抗肿瘤作用，而T @ DOX / VC已被证明是实现有效治疗肿瘤的一种有前途的方法。由于VC引发的表面电荷转换和药物快速释放，T @ DOX / VC（T @ DOX经过VC预处理）显示出优于T @ DOX，R @ DOX和R @ DOX /的增强的细胞毒性和细胞摄取/ VC。T @ DOX / VC还具有良好的体内抗肿瘤作用，与DOX·HCl相当，但毒性副作用比DOX·HCl少。总而言之，VC作为外源性触发剂，可以通过电荷转换诱导具有适当聚合物结构的载药胶束更好的抗肿瘤作用，而T @ DOX / VC已被证明是实现有效治疗肿瘤的一种有前途的方法。与DOX·HCl相当，但毒副作用比DOX·HCl小。总之，VC作为外源性触发剂，可以通过电荷转换诱导具有合适聚合物结构的载药胶束更好的抗肿瘤作用，而T @ DOX / VC已被证明是实现有效治疗肿瘤的一种有前途的方法。与DOX·HCl相当，但毒副作用比DOX·HCl小。总而言之，VC作为外源性触发剂，可以通过电荷转换诱导具有适当聚合物结构的载药胶束更好的抗肿瘤作用，而T @ DOX / VC已被证明是实现有效治疗肿瘤的一种有前途的方法。