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

Abstract

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.

Plasma Device Functions and Tissue Effects in the Female Pelvis—A Systematic Review

“…In vitro studies have been conducted on a wide range of gynaecological cell lines (see also Table 1 in the work of Zubor et al [ 68 ]) of cervical cancer [ 69 , 70 , 71 , 72 ], ovarian cancer [ 73 , 74 , 75 , 76 , 77 , 78 ], and colon cancer [ 79 , 80 , 81 ], see Table 3 . With an aim to increase differences in cell response between healthy and cancer cells, more intricate applications are in development, combining CAP with hyperthermia [ 82 ], radiotherapy [ 72 ], or photodynamic therapy using targeted polymeric nanoparticles [ 83 ].…”

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea

“…In our pilot study, CAP was used as a monotherapy. However, different studies have revealed a great potential of CAP as a combination partner with other, in particular Hofmeyer/Weber/Gerds/Emmert/Thiem oncological, treatments [62][63][64]. In rosacea, using CAP in conjunction with other treatments might also be advantageous due to different aspects: On the one hand, CAP combination with topical drugs might increase their efficacy due to its enhancement of stratum corneum permeabilization [65,66].…”

A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma

“…Photosensitizers are indispensable for PDT. Under light conditions, photosensitizer molecules in the excited state interact with substances such as oxygen and water molecules inside tissues to form free radicals, which contribute to cancer cell damage and apoptosis by elevating intracellular oxidative stress levels ( 32 ). However, electrons in the excited state in photosensitizers are usually unstable and prone to be trapped by electron holes in molecules inside or outside and reattributed to the ground state, thus disfavoring the formation of free radicals ( 33 ).…”