Concerning that the polyethylene glycol surface layer of DOXIL hinders cancer cell uptake, thus leading to low anticancer activity, it is of great importance to promote the cancer cell uptake of liposomal doxorubicin. Herein, we developed the charge-reversal PEGylated liposomal doxorubicin CRDOXIL with enhanced cancer cell uptake and high anticancer activity. Based on the tumor acidity-induced charge-reversal property, the cancer cell uptake of CRDOXIL could be significantly enhanced and the efficient caveolae-mediated endocytosis was achieved. Moreover, CRDOXIL maintained its stable PEGylated structure in neutral normal physiological environment, thus decreasing the side effects of doxorubicin on normal cells. Therefore, CRDOXIL exhibits high anticancer activity to cancer cells and low cytotoxicity against normal cells. It is anticipated that the charge-reversal strategy could be applied in diverse drug delivery systems to meet the requirement in chemotherapy.

关于DOXIL的聚乙二醇表面层阻碍癌细胞摄取，从而导致低的抗癌活性，促进脂质体阿霉素的癌细胞摄取具有重要意义。在这里，我们开发了具有增强的癌细胞摄取和高抗癌活性的电荷逆转聚乙二醇化脂质体阿霉素CRDOXIL。基于肿瘤酸性诱导的电荷逆转特性，可显着提高CRDOXIL的癌细胞摄取，并实现了高效的小窝介导的内吞作用。此外，CRDOXIL在中性正常生理环境中保持其稳定的PEG化结构，从而降低了阿霉素对正常细胞的副作用。因此，CRDOXIL对癌细胞具有高抗癌活性，对正常细胞具有低细胞毒性。