Department of Biomedical Engineering, Daegu Catholic University, Gyeongsan 38430, Korea.
Int J Mol Sci. 2021 Jan 25;22(3):1172. doi: 10.3390/ijms22031172.
Integrating multi-modal therapies into one platform could show great promise in overcoming the drawbacks of conventional single-modal therapy and achieving improved therapeutic efficacy in cancer. In this study, we prepared pheophorbide a (Pheo a)/targeting ligand (epitope analog of oncoprotein E7, EAE7)-conjugated poly(γ-glutamic acid) (γ-PGA)/poly(lactide-co-glycolide)-block-poly(ethylene glycol) methyl ether (MPEG-PLGA)/hyaluronic acid (PPHE) polymeric nanoparticles via self-assembly and encapsulation method for the photodynamic therapy (PDT)/cold atmospheric plasma (CAP) combinatory treatment of human papillomavirus (HPV)-positive cervical cancer, thereby enhancing the therapeutic efficacy. The synthesized PPHE polymeric nanoparticles exhibited a quasi-spherical shape with an average diameter of 80.5 ± 17.6 nm in an aqueous solution. The results from the in vitro PDT efficacy assays demonstrated that PPHE has a superior PDT activity on CaSki cells due to the enhanced targeting ability. In addition, the PDT/CAP combinatory treatment more effectively inhibited the growth of cervical cancer cells by causing elevated intracellular reactive oxygen species generation and apoptotic cell death. Moreover, the three-dimensional cell culture model clearly confirmed the synergistic therapeutic efficacy of the PDT and the CAP combination therapy using PPHE on CaSki cells. Overall, these results indicate that the PDT/CAP combinatory treatment using PPHE is a highly effective new therapeutic modality for cervical cancer.
将多种模式的疗法整合到一个平台上，可能在克服传统单一模式疗法的缺点和提高癌症治疗效果方面具有巨大的潜力。在这项研究中，我们通过自组装和包封方法制备了叶绿酸 a（Pheo a）/靶向配体（癌蛋白 E7 的表位类似物，EAE7）-缀合的聚（γ-谷氨酸）（γ-PGA）/聚（乳酸-共- 乙交酯）-嵌段-聚（乙二醇）甲醚（MPEG-PLGA）/透明质酸（PPHE）聚合物纳米粒子，用于人乳头瘤病毒（HPV）阳性宫颈癌的光动力疗法（PDT）/冷等离体（CAP）联合治疗，从而提高治疗效果。合成的 PPHE 聚合物纳米粒子在水溶液中呈现出准球形形状，平均直径为 80.5 ± 17.6nm。体外 PDT 疗效测定结果表明，由于增强的靶向能力，PPHE 对 CaSki 细胞具有优越的 PDT 活性。此外，PDT/CAP 联合治疗通过增加细胞内活性氧的产生和诱导细胞凋亡，更有效地抑制了宫颈癌细胞的生长。此外，三维细胞培养模型清楚地证实了使用 PPHE 的 PDT 和 CAP 联合治疗对 CaSki 细胞的协同治疗效果。总的来说，这些结果表明，使用 PPHE 的 PDT/CAP 联合治疗是一种治疗宫颈癌的高效新疗法。
