Multifunctional (3-in-1) cancer theranostics applications of hydroxyquinoline-appended polyfluorene nanoparticles

Abstract

The accumulation of fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles and their utility for multi-color bio-imaging and drug delivery for cancer treatment are reported. The formation of nanoparticles (PF-HQ) containing hydrophobic pockets via three-dimensional growth of a polymeric backbone in a higher water fraction (THF : H₂O = 1 : 9) was observed. The nanoparticles showed incredible dual-state optical and fluorescence properties, which were further explored in multi-color cell imaging in both cancer and normal cells. The cell viability assay in various normal cells confirmed the biocompatible nature of PF-HQ, which was further supported by an ex vivo (chick chorioallantoic membrane assay) model. This encouraged us to fabricate PF-HQ-based new drug delivery systems (DDS: PF-HQ–DOX) upon conjugation with the FDA-approved anti-cancer drug doxorubicin (DOX) by filling the hydrophobic pockets of the polymer nanoparticles. The enhanced anti-cancer activity of the DDS (PF-HQ–DOX) compared with that of free DOX was observed in mouse melanoma cancer cells (B16F10) and a subcutaneous mouse (C57BL6/J) melanoma tumor model upon administration of PF-HQ–DOX. Ex vivo biodistribution studies using a fluorescence quantification method demonstrated the enhanced accumulation of DOX in tumor tissues in the PF-HQ–DOX-treated group compared to that of the free drug, signifying the drug delivery efficacy of the delivery system by a passive targeting manner. Based on the above biological data (in vitro and in the pre-clinical model), these robust and versatile fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles could be effectively utilized for multifunctional biomedical applications (as they are biocompatible and can be used for bio-imaging and as a drug delivery vehicle).