Increased photodynamic therapy sensitization in tumors using a nitric oxide-based nanoplatform with ATP-production blocking capability

Photodynamic therapy (PDT) efficacy in cancer cells is affected by sub-physiological hypoxia caused dysregulated and chaotic tumor microvasculature. However, current traditional O2-replenishing strategies are undergoing their own intrinsic deficiencies. In addition, resistance mechanisms activated during PDT also lead the present situation far from satisfactory. Methods: We propose a nitric oxide (NO)-based theranostic nanoplatform using biocompatible poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) as carriers, which outer polymeric layer embeds chlorin e6 (Ce6) incorporates L-Arginine (L-Arg). This (L-Arg@Ce6@P can reduce hyperactive O2 metabolism of NO-mediated mitochondrial respiration inhibition, should raise endogenous tension to counteract hypoxia. Furthermore, NO hinder oxidative phosphorylation (OXPHOS) cause intracellular adenosine triphosphate (ATP) depletion, inhibiting proliferation turning more sensitive PDT. Results: When L-Arg@Ce6@P NPs accumulate solid tumors enhanced permeability retention (EPR) effect, locally released L-Arg oxidized abundant H2O2 produce NO. vitro experiments suggest that retard hypoactive save for enhancing under NIR light irradiation. Also, lower ATP hinders DNA, improving sensitization. phototherapeutic increased combining these two complementary vitro/in vivo. Conclusion: show this NO-based be potentially used alleviate sensitize amplify phototherapy guided photoacoustic (PA) imaging.