Department of Chemistry, Faculty of Science, Chulalongkorn University , Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
Program in Biotechnology, Faculty of Science, Chulalongkorn University , Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
Mol Pharm. 2018 Jan 2;15(1):164-174. doi: 10.1021/acs.molpharmaceut.7b00780. Epub 2017 Dec 18.
A zwitterionic copolymer between methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid (MA), PMAMPC is introduced as a potential versatile polymeric stabilizer for gold nanorods (AuNRs). The MA units in the copolymer serve as built-in feature for multiple functionalization, namely introducing additional thiol groups as active sites for binding with the AuNRs and conjugating with doxorubicin (DOX), an anticancer drug via acid-labile hydrazone linkage. The MPC units, on the other hand, provide biocompatibility and antifouling characteristics. The chemically modified PMAMPC can act as an effective stabilizer for AuNRs yielding PMAMPC-DOX-AuNRs with a fairly uniform size and shape with good colloidal stability. In vitro cytotoxicity suggested that PMAMPC can not only improve the AuNRs biocompatibility, but also decrease DOX toxicity to a certain extent. The PMAMPC-DOX-AuNRs were efficiently internalized inside cancer cells and localized in lysosomes, where DOX was presumably acid-triggered released as monitored by confocal laser scanning microscopic analysis and flow cytometry. Furthermore, the combined photothermal-chemo treatment of cancer cells using PMAMPC-DOX-AuNRs exhibited a higher therapeutic efficacy than either single treatment alone. These results suggested that the PMAMPC-DOX-AuNRs could potentially be applied in pH-triggered drug delivery for synergistic cancer therapy.
聚（甲基丙烯酰氧乙基磷酰胆碱-甲基丙烯酸酯）（PMAMPC）是一种甲基丙烯酰氧乙基磷酰胆碱（MPC）和甲基丙烯酸（MA）的两性离子共聚物，被引入作为金纳米棒（AuNRs）的潜在通用聚合物稳定剂。共聚物中的 MA 单元作为内置功能，可以进行多种功能化，即引入额外的巯基作为与 AuNRs 结合的活性位点，并通过酸不稳定的腙键与阿霉素（DOX）结合，DOX 是一种抗癌药物。另一方面，MPC 单元提供生物相容性和抗污特性。化学修饰的 PMAMPC 可以作为 AuNRs 的有效稳定剂，得到具有相当均匀的尺寸和形状以及良好胶体稳定性的 PMAMPC-DOX-AuNRs。体外细胞毒性实验表明，PMAMPC 不仅可以提高 AuNRs 的生物相容性，而且在一定程度上降低 DOX 的毒性。PMAMPC-DOX-AuNRs 被有效地内吞到癌细胞内部，并定位于溶酶体中，在那里 DOX 被推测在酸性条件下释放，这可以通过共聚焦激光扫描显微镜分析和流式细胞术监测到。此外，使用 PMAMPC-DOX-AuNRs 进行光热-化疗联合治疗癌细胞的效果比单一治疗更高。这些结果表明，PMAMPC-DOX-AuNRs 可能应用于 pH 触发的药物传递，用于协同癌症治疗。
