title: Apoferritin Nanocage Delivers Combination of Microtubule and Nucleus Targeting Anticancer Drugs.
abstract: An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics and competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find such a unique nanocarrier and to engineer all of the above-mentioned features into it. In this manuscript, we have shown for the first time that apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc), and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation. In addition, we have shown that Apf alone is noncytotoxic in nature and interacts with intracellular tubulin/microtubule. Drug loaded Apf specifically bound and consequently internalized into the human breast cancer cell line (MCF7) and human cervical cancer cell line (HeLa) through receptor mediated endocytosis process and releases either single or combination of drugs in the endosome. We have also checked the binding efficacy of both drugs using molecular docking. Further, using fluorescence microscopy, we have shown that Apf can deliver combination of drugs inside cancer cells and the drugs exerts their effect thereof. Finally, we have studied the efficacy of Apf complexes with individual drugs and in combination compared to free drugs in a tumor mimicking 3D multicellular spheroid model of HeLa cell.
authors: Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors: Subhajit
authors: S
authors: Ghosh
authors: Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology Campus , 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Saswat
authors: S
authors: Mohapatra
authors: Department of Chemistry, Indian Institute of Technology Kanpur , Kanpur 208016, India.
authors: Anisha
authors: A
authors: Thomas
authors: Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors: Debmalya
authors: D
authors: Bhunia
authors: Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors: Abhijit
authors: A
authors: Saha
authors: Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology Campus , 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Gaurav
authors: G
authors: Das
authors: Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors: Batakrishna
authors: B
authors: Jana
authors: Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Biology Campus , 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Surajit
authors: S
authors: Ghosh
mesh_terms: D000970:Antineoplastic Agents; D001052:Apoferritins / Q000737:chemistry*; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D004317:Doxorubicin; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules; D062105:Molecular Docking Simulation; D049329:Nanostructures
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin; D001052:Apoferritins
keywords: apoferritin; cancer cell; combination therapy; drug delivery; spheroid; tubulin/microtubule