In situ pain relief during photodynamic therapy by ROS-responsive nanomicelle through blocking VGSC.

Pain in photodynamic therapy (PDT), resulting from the stimulation of reactive oxygen species (ROS) and local acute inflammation, is a primary side effect of PDT that often leads to treatment interruption or termination, significantly compromising the efficacy of PDT and posing an enduring challenge for clinical practice. Herein, a ROS-responsive nanomicelle, poly(ethylene glycol)-b-poly(propylene sulphide) (PEG-PPS) encapsulated Ce6 and Lidocaine (LC), (ESCL) was used to address these problems. The tumor preferentially accumulated micelles could realize enhanced PDT effect, as well as in situ quickly release LC due to its ROS generation ability after light irradiation, which owes to the ROS-responsive property of PSS. In addition, PSS can suppress inflammatory pain which is one of the mechanisms of PDT induced pain. High LC-loaded efficiency (94.56 %) owing to the presence of the thioether bond of the PPS made an additional pain relief by inhibiting excessive inflammation besides blocking voltage-gated sodium channels (VGSC). Moreover, the anti-angiogenic effect of LC offers further therapeutic effects of PDT. The in vitro and in vivo anti-tumor results revealed significant PDT efficacy. The signals of the sciatic nerve in mice were measured by electrophysiological study to evaluate the pain relief, results showed that the relative integral area of neural signals in ESCL-treated mice decreased by 49.90 % compared to the micelles without loaded LC. Therefore, our study not only develops a very simple but effective tumor treatment PDT and in situ pain relief strategy during PDT, but also provides a quantitative pain evaluation method.

Improved Simulated-Daylight Photodynamic Therapy and Possible Mechanism of Ag-Modified TiO2 on Melanoma.

Simulated-daylight photodynamic therapy (SD-PDT) may be an efficacious strategy for treating melanoma because it can overcome the severe stinging pain, erythema, and edema experienced during conventional PDT. However, the poor daylight response of existing common photosensitizers leads to unsatisfactory anti-tumor therapeutic effects and limits the development of daylight PDT. Hence, in this study, we utilized Ag nanoparticles to adjust the daylight response of TiO2, acquire efficient photochemical activity, and then enhance the anti-tumor therapeutic effect of SD-PDT on melanoma. The synthesized Ag-doped TiO2 showed an optimal enhanced effect compared to Ag-core TiO2. Doping Ag into TiO2 produced a new shallow acceptor impurity level in the energy band structure, which expanded optical absorption in the range of 400-800 nm, and finally improved the photodamage effect of TiO2 under SD irradiation. Plasmonic near-field distributions were enhanced due to the high refractive index of TiO2 at the Ag-TiO2 interface, and then the amount of light captured by TiO2 was increased to induce the enhanced SD-PDT effect of Ag-core TiO2. Hence, Ag could effectively improve the photochemical activity and SD-PDT effect of TiO2 through the change in the energy band structure. Generally, Ag-doped TiO2 is a promising photosensitizer agent for treating melanoma via SD-PDT.