Shockwave‐Assisted Delivery of Berries‐Conjugated Carbon Dots Nanoparticles for Shockwave–Photodynamic Bladder Cancer Treatment

Background: Shockwave–photodynamic therapy (SWPDT) is a novel approach to cancer treatment that combines photodynamic therapy (PDT) and shockwave–dynamic therapy (SWDT) with sensitizers. Although several novel sensitizers for SWPDT have been successfully synthesized, not all of them are being used to their full potential. The tumor microenvironment’s degradation, the sensitizers’ limited capacity to transfer deeply intratumorally, and their restricted tumor‐targeting specificity all contribute to their low antitumor efficacy. To provide an advanced strategy for cancer treatment, this study was conducted with the aim of shockwave (SW)‐assisted drug administration of berries‐conjugated carbon dots (CDs) nanoparticles for in vitro and in vivo SW–photodynamic bladder cancer (BLCA) treatment. Materials and Methods: This study was conducted on BLCA (T‐24) human cells in vitro and on Swiss albino mice in vivo, where the mice were administered only N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) without receiving any treatment for inducing BLCA. The treatment protocol for the BLCA induction study was initiated after the mice BLCA began, and it involved daily administration of Berries‐CDsNP with or without SW and/or laser (IRL) exposure for 3 minutes over a 2‐week period. We used Berries‐CDsNP as SWPDT sensitizer (SWPS), with IRL and SW serving as two sources of energy. Results: The results demonstrated that CDs could be employed as an efficient delivery system for berries to the target BLCA cells. Furthermore, Berries‐CDsNP is a potential SWPS that can be highly successful in treating BLCA‐T‐24 in vitro when combined with SWPDT (cell viability was declined, cell cycle was arrested, and cell death was induced; in a dose‐dependent manner, the population of cells during the G0/G1 phase increased, an increase in the Pre‐G cell population, autophagic cell death, apoptosis early/late phases, and necrosis were observed) and in vivo (BBN‐induced BLCA mice) induction of antiproliferative apoptotic (Bax, p53, TNF‐alpha, Caspase‐3, and Caspase‐9) genes, suppression of antiangiogenic (VEGF) and antiapoptotic (Bcl2) genes, efficiently eliminating cancer cells, restoring deteriorated parameter, enhancing the functions of the kidneys (urea and creatinine) and liver (ALT and AST), conserving redox status homeostasis via regaining antioxidant balance (GPx, GSH, GR, GST, SOD, CAT, and TAC), and lowering oxidative stress (MDA). This process can be connected to sensitization of berries upon the SW and photochemical SWPDT activation mechanism and the antioxidant potential of nonactivated berries. Conclusion: Our research findings indicate that the Berries‐CDsNP shows significant potential as an innovative and effective delivery strategy for SWPDT‐activated BLCA treatment.