Photodynamic and Cold Atmospheric Plasma Combination Therapy Using Polymeric Nanoparticles for the Synergistic Treatment of Cervical Cancer

• Published in: International journal of molecular sciences 2021-01, Vol.22 (3), p.1172
• Main Authors: Ha, Ji-Hui, Kim, Young-Jin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Aqueous solutions; Biomarkers; Cancer therapies; Cell culture; Cell death; Cell Line; Cell Survival; Cervical cancer; Cervix; cold atmospheric plasma; Combination therapy; Combined Modality Therapy; Deoxyribonucleic acid; Disease Management; DNA; Drug delivery systems; Epitopes; Female; Glutamic acid; Human papillomavirus; Humans; Hyaluronic acid; Ligands; Molecular Imaging; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; NMR; Nuclear magnetic resonance; Photochemotherapy - methods; Photodynamic therapy; Plasma; Plasma Gases - therapeutic use; Poly(lactide-co-glycolide); Polyesters - chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemistry; Polylactide-co-glycolide; polymeric nanoparticles; Polymers - chemistry; Reactive oxygen species; Reactive Oxygen Species - metabolism; Self-assembly; Spectrum analysis; Treatment Outcome; Uterine Cervical Neoplasms - diagnostic imaging; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.