title: An Integrin-Targeting RGDK-Tagged Nanocarrier: Anticancer Efficacy of Loaded Curcumin.
abstract: Herein we report the design and development of α5β1integrin-specific noncovalent RGDK-lipopeptide-functionalized single-walled carbon nanotubes (SWNTs) that selectively deliver the anticancer drug curcumin to tumor cells. RGDK tetrapeptide-tagged amphiphiles were synthesized that efficiently disperse SWNTs with a suspension stability index of >80 % in cell culture media. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)- and lactate dehydrogenase (LDH)-based cell viability assays in tumor (B16F10 melanoma) and noncancerous (NIH3T3 mouse fibroblast) cells revealed the non-cytotoxic nature of these RGDK-lipopeptide-SWNT conjugates. Cellular uptake experiments with monoclonal antibodies against αvβ3, αvβ5, and α5β1integrins showed that these SWNT nanovectors deliver their cargo (Cy3-labeled oligonucleotides, Cy3-oligo) to B16F10 cells selectively via α5β1integrin. Notably, the nanovectors failed to deliver the Cy3-oligo to NIH3T3 cells. The RGDK-SWNT is capable of delivering the anticancer drug curcumin to B16F10 cells more efficiently than NIH3T3 cells, leading to selective killing of B16F10 cells. Results of Annexin V binding based flow cytometry experiments are consistent with selective killing of tumor cells through the late apoptotic pathway. Biodistribution studies in melanoma (B16F10)-bearing C57BL/6J mice showed tumor-selective accumulation of curcumin intravenously administered via RGDK-lipopeptide-SWNT nanovectors.
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Das
authors.affiliation: Biomaterials Group, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Sahithi
authors.initials: S
authors.lastname: Nimushakavi
authors.affiliation: Biomaterials Group, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Arabinda
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
authors.forename: Prasanta Kumar
authors.initials: PK
authors.lastname: Das
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D039081:Integrin alpha5beta1; D037742:Nanotubes, Carbon; D009842:Oligopeptides; D003474:Curcumin
keywords: cancer; curcumin; drug delivery; integrins; nanotubes; oligonucleotides