Transferrin Tethered Fluorescent Organic Nanoparticles for Receptor‐Mediated Targeted Delivery of Paclitaxel to Cancer Cells

Cancer remains a critical global issue, marked by its high mortality rates. Despite achieving remarkable progress in cancer treatments, conventional chemotherapeutic drugs face numerous limitations. To this end, nanomaterial-based targeted drug delivery systems have emerged as a hope of promise. In this study, we report the design and development of transferrin (Tf) tethered naphthalene-diimide-based fluorescent organic nanoparticles (NDI-OH-Tf) for targeted delivery of paclitaxel to cancer cells with over expressed transferrin receptors (TfR). Spherical NDI-OH FONPs were fabricated through J-type of aggregation of NDI-OH amphiphiles in a 1:99 (v/v) DMSO-H₂O mixture. These NDI-OH FONPs exhibited aggregation induced emission (AIE) at an emission wavelength of λ_em = 594 nm. The hydroxyl groups on the surface of the NDI-OH FONPs were conjugated with carboxyl groups of transferrin, forming NDI-OH-Tf FONPs. These NDI-OH-Tf FONPs were successfully used for targeted bioimaging and drug delivery to TfR+ cancer cells through ligand receptor interaction between transferrin and TfR. Notably, paclitaxel loaded NDI-OH-Tf exhibited ∼2.9-fold higher efficacy toward TfR+ cancer cells compared to normal cells and ∼3.3-fold higher cytotoxicity than free PTX due to transferrin mediated targeted accumulation of PTX in cancer cells.