Dacarbazine-primed carbon quantum dots coated with breast cancer cell-derived exosomes for improved breast cancer therapy

• Published in: Journal of controlled release 2024-01, Vol.365, p.43-59
• Main Authors: Tiwari, Pratiksha, Shukla, Ravi Prakash, Yadav, Krishna, Singh, Neha, Marwaha, Disha, Gautam, Shalini, Bakshi, Avijit Kumar, Rai, Nikhil, Kumar, Ankit, Sharma, Deepak, Mishra, Prabhat Ranjan
• Format: Article
• Language: English
• Subjects: apoptosis; breast neoplasms; cancer therapy; carbon; drug therapy; exosomes; heparan sulfate; membrane potential; mitochondrial membrane; nanocarriers; nanoparticles; pharmacokinetics; proteoglycans; toxicity
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2023.11.005

Imprecise targeting of chemotherapeutic drugs often leads to severe toxicity during breast cancer therapy. To address this issue, we have devised a strategy to load dacarbazine (DC) into fucose-based carbon quantum dots (CQDs), which are subsequently coated with exosomes (Ex-DC@CQDs) derived from breast cancer cells. Nanoparticle tracking analysis and western blotting revealed that Ex-DC@CQDs retained the structural and functional characteristics of exosomes. We found that exosomes facilitated the transport of DC@CQDs to cancer cells via heparan sulfate proteoglycan (HSPG) receptors, followed by an augmented depolarization of the mitochondrial membrane potential, ROS generation, and induction of apoptosis leading to cell death. In vivo imaging and pharmacokinetic studies demonstrated enhanced antitumor targeting and efficacy compared to free DC which we attribute to an improved pharmacokinetic profile, a greater tumor accumulation via exosome-mediated- HSPG receptor-driven cell uptake, and sustained release of the Ex-DC@CQDs. Our findings may pave the way for the further development of biologically sourced nanocarriers for breast cancer targeting.