Doxorubicin-loaded pH-responsive porphyrin-derived carbon dots as a promising biocompatible drug delivery system for effective chemotherapy of breast cancer

Abstract

Doxorubicin (DOX), a widely used chemotherapy drug for breast cancer, suffers from limitations such as non-specific toxicity and drug resistance. To address these challenges, we developed a novel drug delivery system (DDS) using porphyrin-derived carbon dots (CDs) as carriers for DOX. Porphyrin-based CDs were synthesized solvothermally from tetrakis(4-carboxyphenyl) porphyrin (TCPP) and urea. DOX was non-covalently loaded onto the CDs to form the DOX@CDs nanocomposite. The resulting CDs exhibited desirable properties like excellent water solubility, stability, and biocompatibility. Moreover, the DOX@CDs complex showed a high drug loading efficiency of 93% and a pH-responsive release profile, with enhanced release at acidic tumor microenvironments. The DOX@CDs nanocomposite demonstrated significantly improved cytotoxicity against human breast cancer MCF-7 and MDA-MB-231 cell lines (at IC₅₀ values 24.08 ± 1.446 and 10.587 ± 0.815 μg mL⁻¹) compared to free DOX (at IC₅₀ values = 262.96 ± 1.807 and 261.6 ± 0.907 μg mL⁻¹). Analysis by fluorescence microscopy and flow cytometry demonstrated that the enhanced cytotoxicity of the DOX@CDs complex compared to free DOX correlated with its greater cellular uptake and localization in cancerous cells. Notably, the nanocomposite exhibited reduced hemolytic activity, indicating enhanced biocompatibility. Our findings suggest that porphyrin-derived CDs hold promise as a safe and effective nanocarrier for targeted DOX delivery, offering a potential strategy to improve the therapeutic efficacy of breast cancer chemotherapy.