Nanogel–Carbon Dot Conjugates: A Synergistic Approach for Enhanced Cancer Treatment through Combination Therapy

The present study reports the development of a novel nanoconjugate, <b>NG-FACD</b>, comprising a positively charged self-assembled nanogel (NG) derived from a peptide amphiphilic hydrogelator and a negatively charged folic acid-functionalized blue-emitting carbon dot (FACD), bound via electrostatic interactions. <b>NG-FACD</b> was developed to combine the advantages of the individual nanocarriers and overcome their drawbacks. The presence of folic acid enables <b>NG-FACD</b> to be successfully used in selective bioimaging and targeted combination therapy against folate receptor-positive (FR+) B16F10 over FR- cells. <b>NG-FACD</b> demonstrated improved riboflavin (RbF) and paclitaxel (PTX) loading compared to individual nanocarriers that made it ∼1.8- and 1.5-fold more cytotoxic toward FR+ B16F10 cells over RbF- and PTX-loaded individual nanocarriers. The concurrent presence of RbF and PTX on <b>NG-FACD</b> displayed ∼1.9-2.8-fold higher cytotoxicity than single drug-loaded individual nanocarriers and ∼3-4.5-fold higher cytotoxicity through RbF-mediated photodynamic therapy and PTX-induced chemotherapy in synergy compared to free drugs against FR+ B16F10 cells.