Tryptophan-Conjugated Carbon Dots with Enhanced Cellular Uptake as a Potential Drug Delivery System for Melanoma

Melanoma is a rare but highly aggressive form of skin cancer that can rapidly metastasize, leading to a significant mortality rate. A main challenge in chemotherapy is the lack of selectivity in drug delivery to tumor sites, which affects both tumor and healthy tissues. Developing drug delivery systems (DDS) capable of preferentially interacting with transporters expressed on cancer cells may help address this issue. Carbon dots (CDs) have emerged as promising tools for the advancement of DDS due to their distinctive fluorescent characteristics, good water solubility, biocompatibility, and straightforward fabrication. In this work, CDs were synthesized via a facile method and conjugated with tryptophan (Trp) to evaluate their potential application as a DDS in melanoma. The fabricated CDs were characterized for their size, surface charge, optical properties, functional groups, and elemental analysis. LAT1 expression was examined by immunofluorescence, confirming higher levels in SK-MEL-2 melanoma cells compared to HK-2 normal kidney cells. Biocompatibility was established before conjugating CDs with tryptophan (Trp), ditryptophan (di-Trp), and tritryptophan (tri-Trp) and assessing their size, functional groups, and optical characteristics. Cellular uptake studies showed preferential uptake of Trp-conjugated CDs in SK-MEL-2 cells over HK-2 cells, indicating that tri-Trp-CDs exhibited the highest uptake. Molecular dynamics simulations suggested potential CDs-LAT1 interactions via van der Waals and electrostatic interactions. Trp-conjugated CDs were biocompatible with both SK-MEL-2 and HK-2 cells and could be electrostatically loaded with doxorubicin (DOX), exhibiting enhanced cytotoxicity against SK-MEL-2 cells compared to DOX alone. A trend toward greater selectivity for SK-MEL-2 cells over normal cells was observed, with tri-Trp/DOX showing the most pronounced effect, possibly reflecting LAT1-1 mediated uptake. These findings suggest that Trp-modified CDs may serve as promising DDS candidates for melanoma treatment.