Bismuth/manganese-doped carbon dots in calcium phosphate matrix: Dynamic conformational nanoparticles enhancing tumor accumulation, deep penetration, and radiosensitivity

Radiotherapy is a cornerstone in the treatment of malignant tumors, yet its efficacy is often hindered by intrinsic and acquired resistance mechanisms, notably limited radiation availability and tumor hypoxia within inner tumor region. This study introduces a multifunctional nanosensitizer, CD Bi,Mn-FA @CaP, with high tumor accumulation and deep penetration capabilities via dynamic conformational change. CD Bi,Mn-FA was bismuth manganese-doped carbon dots, offering radiosensitizing properties and catalase-like activity for oxygen generation. Folic acid modification further enhances tumor cell targeting. These carbon dots are encapsulated in calcium phosphate nanoparticles to form CD Bi,Mn-FA @CaP, which demonstrates improved in vivo circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. Upon encountering the acidic tumor microenvironment, the encapsulation degrades, releasing smaller CD Bi,Mn-FA particles that deeply penetrate tumor tissues. In vitro and in vivo experiments establish that CD Bi,Mn-FA @CaP effectively targets tumor tissue, enhances radiotherapy-induced apoptosis, and suppresses tumor growth. Notably, the nanoparticle achieves a 40 % tumor cure rate and ensures 100 % survival within 45 days post-treatment. Biocompatibility studies confirm minimal systemic impact, with efficient renal and fecal elimination, indicating promising clinical translational potential. This study introduces a novel radiation therapy sensitization strategy and underscores the potential of such size changeable nanoparticles as an advanced targeted drug delivery system for tumors.