Nanotechnology, Science and Applications (Mar 2021)
Water-Soluble Chitosan Conjugated DOTA-Bombesin Peptide Capped Gold Nanoparticles as a Targeted Therapeutic Agent for Prostate Cancer
Abstract
Theeranan Tangthong,1,2 Thananchai Piroonpan,2 Velaphi C Thipe,3,4 Menka Khoobchandani,4,5 Kavita Katti,4,5 Kattesh V Katti,4– 6 Wanvimol Pasanphan1,2 1Department of Materials Science, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand; 2Center of Radiation Processing for Polymer Modification and Nanotechnology (CRPN), Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand; 3Laboratório de Ecotoxicologia - Centro de Química e Meio Ambiente - Instituto de Pesquisas Energéticase Nucleares (IPEN) - Comissão Nacional de Energia Nuclear- IPEN/CNEN-SP, São Paulo, Brasil; 4Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65211, USA; 5Department of Radiology, University of Missouri, Columbia, MO, 65211, USA; 6Department of Physics, University of Missouri, Columbia, MO, 65211, USACorrespondence: Wanvimol PasanphanDepartment of Materials Science, Faculty of Science, Kasetsart University, 50 Ngam Wong Wan Road, Lat Yao, Chatuchak, Bangkok, 10900, ThailandTel +66 2562 5555 (Ext. 646518)Email [email protected] V KattiInstitute of Green Nanotechnology, University of Missouri, Columbia, MO, 65211, USATel +1 573 882-5656Fax +1 573 884-5679Email [email protected]: Functionalization of water-soluble chitosan (WSCS) nanocolloids with, gold nanoparticles (AuNPs), and LyslLys3 (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-bombesin 1– 14 (DOTA-BBN) peptide affords an innovative pathway to produce prostate tumor cell-specific nanomedicine agents with potential applications in molecular imaging and therapy.Methods: The preparation involves the production and full characterization of water-soluble chitosan (WSCS), via gamma (γ) rays (80 kGy) irradiation, followed by DOTA-BBN conjugation for subsequent use as an effective template toward the synthesis of tumor cell-specific AuNPs-WSCS-DOTA-BBN.Results: The WSCS-DOTA-BBN polymeric nanoparticles (86 ± 2.03 nm) served multiple roles as reducing and stabilizing agents in the overall template synthesis of tumor cell-targeted AuNPs. The AuNPs capped with WSCS and WSCS-DOTA-BBN exhibited average Au-core diameter of 17 ± 8 nm and 20 ± 7 nm with hydrodynamic diameters of 56 ± 1 and 67± 2 nm, respectively. The AuNPs-WSCS-DOTA-BBN showed optimum in vitro stability in biologically relevant solutions. The targeted AuNPs showed selective affinity toward GRP receptors overexpressed in prostate cancer cells (PC-3 and LNCaP).Discussion: The AuNPs-WSCS-DOTA-BBN displayed cytotoxicity effects against PC-3 and LNCaP cancer cells, with concomitant safety toward the HAECs normal cells. The AuNPs-WSCS-DOTA-BBN showed synergistic targeting toward tumor cells with selective cytotoxicity of AuNPs towards PC-3 and LNCaP cells. Our investigations provide compelling evidence that AuNPs functionalized with WSCS-DOTA-BBN is an innovative nanomedicine approach for use in molecular imaging and therapy of GRP receptor-positive tumors. The template synthesis of AuNPs-WSCS-DOTA-BBN serves as an excellent non-radioactive surrogate for the development of the corresponding 198AuNPs theragnostic nanoradiopharmaceutical for use in cancer diagnosis and therapy.Keywords: DOTA-bombesin, gold nanoparticle, water-soluble chitosan, nanoradiopharmaceutical, prostate cancer
