Zwitterionic Poly(carboxybetaine) Modified Liposomes for Anti-Tumor Therapy: An In Vitro Study

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Although PEGylated liposomes are a promising application for anti-tumor therapy due to achieving a longer circulation time for the delivery drugs to a tumor via the enhanced permeability and retention (EPR) effect, PEG interferes with antibody-antigen binding, reducing cellular uptake. In this study, we developed a targeted zwitterionic poly(carboxybetaine) (PCB) modified liposomes for anti-tumor therapy in vitro study. PCB raises the polarity of the aqueous phase and enhance the hydration of lipid polar group regions, thus avoiding those membrane-destabilizing issues of PEG. The liposomes were encapsulated with doxorubicin (DOX), which is widely used clinically because of its broad spectrum anti-tumor activity, such as breast cancer and ovarian cancer. Phospholipid DPPE and Cholesterol was modified with PCB. Both modified lipid were used to prepare liposomes. In addition, DPPE-PCB was conjugated with folic acid, which further improved the active targeting to tumors and minimized the nonspecific uptake by normal cells. The FA-PCB-DPPE liposomes were much stable and showed higher cellular uptake to murine breast carcinoma 4T1 cells which overexpressing the folate receptor but not to L929 fibroblast cells. The liposomes composed of DSPC, CHOL-PCB, and DPPE-PCB also achieved high stability; however, due to its prolonged retention, with the lack of targeted effect to cells, the drug could not reach the cells effectively. The results of different liposomes in cell viability were consistent with the results from cellular uptake. PCB-modified liposomes provided slower drug leakage and higher stability than PEGylated liposomes. Furthermore, The FA-PCB-DPPE liposomes loaded with DOX exhibited slowly drug leakage rates, which was similar to DPPE-PCB and DSPE-PEG liposomes. These results indicated that targeted PCB-modified liposomes have great potential as a drug delivery system in anti-tumor therapy.