Concurrent targeted delivery of doxorubicin and curcumin to the cancer cells using simple and versatile ligand-installed multifaceted chitosan-based nanoconjugates

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 13; no. 7; pp. 249 - 253
• Main Authors: Barman, Sourav, Roy, Sayoni Maitra, Kishore, Purvi, Ghosh, Malabika, Bag, Pousali, Sarkar, Ankan Kumar, Ghatak, Tapas, Maji, Partha Sona, Basu, Arnab, Mukherjee, Rupam, Ghosh, Surya K, Chowdhury, Ankan Dutta, Maity, Amit Ranjan
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 12.02.2025
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chitosan; Chitosan - chemistry; Cholesterol; Curcumin; Curcumin - chemistry; Curcumin - pharmacology; Cytosol; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug development; Drug interaction; Drug Screening Assays, Antitumor; Drugs; Folic acid; Folic Acid - chemistry; Graft copolymers; Humans; Hydrophobicity; Immunosuppressive agents; KB cells; Ligands; Nanoconjugates - chemistry; Particle Size; Polymers; Toxicity; Tumors
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb01809e

Existing chemotherapeutic approaches against refractory cancers are ineffective due to off-target effects, inefficient delivery, and inadequate accumulation of anticancer drugs at the tumor site, which causes limited efficiency of drug treatment and toxicity to neighboring healthy cells. The development of nano-based drug delivery systems (DDSs) with the goal of delivering desired therapeutic doses to the diseased cells and has already proven to be a promising strategy to address these challenges. Our study focuses on achieving an efficient tumor-targeted delivery of a combination of drugs for therapeutic benefits by developing a versatile DDS by following a simple one-step chemical approach. We used low-molecular-weight chitosan and modified its primary amine groups with reactive forms of cholesterol and folic acid by simple chemical tools and thus prepared folic acid-chitosan-cholesterol graft copolymer. The polymer contains numerous residual primary amine groups, which offer enough water solubility and positive charge to its polymeric backbone to foster the interaction of negatively charged and/or hydrophobic drugs to load and encapsulate a wide variety of drugs within it via various non-bonding interactions. We used curcumin and doxorubicin as the combination of drugs and thus finally prepared targeted nanoconjugates (targeted NCs). In vitro cellular experiments show that our developed targeted NCs demonstrate 3-5 times higher cellular uptake than non-targeted NCs at various incubation times (2 h, 8 h, and 12 h) in KB cells where folate receptors are overexpressed. This enhanced cellular uptake of targeted NCs and the following delivery of drugs in the cytosol and its disposition to the nucleus exhibit a substantial amount of toxicity to KB cells towards an effective therapeutic strategy for treatment. Targeted nanoconjugates loaded with combination of drugs delivered to cancer cells and exhibited significant cytotoxic effects.