Preparation Of Multifunctional Folate Carbon Dots And Study Of Anti-tumor Activity

Photodynamic therapy（PDT）and chemodynamic therapy（CDT）are promising new cancer treatment methods mediated by reactive oxygen species（ROS）,with the advantages of minimally invasive,non-multi-drug resistance,no systemic toxicity,and local selectivity.However,due to the influence of tumor microenvironment（TME）and poor tumor-targeting,the therapeutic effect has been seriously reduced.Carbon dots（CDs）have great potential for development in the diagnosis and treatment of cancer due to their unique properties.The research content of this paper is divided into two parts.1.Organic disulfide-modified folate carbon dots for tumor-targeted synergistic chemodynamic/photodynamic therapy.3,3’-dithiodipropionic acid（DTPA）and Pyropheophorbide-a（PPa）modified folate carbon dots FCPPD were prepared for tumor treatment.Based on the synergistic effect of Photo-chemodynamic therapy,the restriction of tumor microenvironment was overcome,and the glutathione（GSH）consumption of disulfides cascaded to amplify the ROS level.FCPPD is targeted and enriched at tumor sites mediated by folate receptor（FR）.The Fenton-Like reaction of folate carbon dots were reported for the first time.It catalyzes the decomposition of hydrogen peroxide in tumor cells to generate cytotoxic hydroxyl radicals,and kills cancer cells with the assistance of glutathione consumed by disulfide bonds.This demonstrates the potential application of metal free carbon dots in diagnosis and treatment.In vitro and in vivo experiments,FCPPD exhibits excellent anti-tumor activity.This study provides a new idea for the design of multifunctional anti-tumor carbon dots.2.Carbon dots@layered double hydroxides nanocomplexes for multi-modal cancer synergistic therapy.A highly efficient multi-modal combined anti-tumor nanoplatform LDHs@CDs@HA was prepared with the ability to deplete GSH（DG）in large quantities,possessing p H sensor capability and effective inactivation of cancer cells by combined CDT/PTT effect.CuCoFe-LDHs can catabolize tumor endogenous H₂O₂ overexpression by CDT effect and provide oxygen and significantly downregulate the expression of hypoxic factor HIF-1α.The surface modification of LDHs using red light carbon dot R-CDs with PTT effect enhanced the PTT effect.Meanwhile,enhanced PTT can effectively improve CDT treatment.HA provides cellular CD44 target specificity and wrapping HA can effectively enhance LDHs aqueous solubility.LDHs@CDs@HA has tumor targeting and powerful CDT/PTT/DG synergistic therapeutic ability,which significantly enhances host immunogenicity.Combined with anti-PD-L1immune checkpoint blockade therapy can achieve a systemic anti-tumor immune response,fundamentally remove the primary tumor,effectively suppress untreated distal tumors,and hopefully inhibit tumor metastasis.