title: Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and In Vivo Studies.
abstract: The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.
authors.affiliation: Department of Inorganic and Physical Chemistry, ‡Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore- 560012, India.
authors.forename: Anup K
authors.initials: AK
authors.lastname: Pramanik
authors.affiliation: Department of Inorganic and Physical Chemistry, ‡Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore- 560012, India.
authors.lastname: Siddikuzzaman
authors.affiliation: Department of Inorganic and Physical Chemistry, ‡Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore- 560012, India.
authors.forename: Duraippandi
authors.initials: D
authors.lastname: Palanimuthu
authors.affiliation: Department of Inorganic and Physical Chemistry, ‡Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore- 560012, India.
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Somasundaram
authors.affiliation: Department of Inorganic and Physical Chemistry, ‡Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore- 560012, India.
authors.forename: Ashoka G
authors.identifier: http://orcid.org/0000-0001-9416-162X
authors.initials: AG
authors.lastname: Samuelson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D003300:Copper / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006046:Gold / Q000737:chemistry; D006801:Humans; D008819:Mice, Nude; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D008063:Thioctic Acid / Q000737:chemistry; D013882:Thiosemicarbazones / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D058726:Nanoconjugates; D013882:Thiosemicarbazones; D011092:Polyethylene Glycols; D001710:Biotin; D008063:Thioctic Acid; D006046:Gold; D003300:Copper