Water-Soluble Chitosan Conjugated DOTA-Bombesin Peptide Capped Gold Nanoparticles as a Targeted Therapeutic Agent for Prostate Cancer

Theeranan Tangthong; Thananchai Piroonpan; Velaphi C Thipe; Menka Khoobchandani; Kavita Katti; Kattesh V Katti; Wanvimol Pasanphan

doi:10.2147/NSA.S301942

Water-Soluble Chitosan Conjugated DOTA-Bombesin Peptide Capped Gold Nanoparticles as a Targeted Therapeutic Agent for Prostate Cancer

Nanotechnol Sci Appl. 2021 Mar 18:14:69-89. doi: 10.2147/NSA.S301942. eCollection 2021.

Authors

Theeranan Tangthong^{1

2}, Thananchai Piroonpan², Velaphi C Thipe^{3

4}, Menka Khoobchandani^{4

5}, Kavita Katti^{4

5}, Kattesh V Katti^{4

5

6}, Wanvimol Pasanphan^{1

2}

Affiliations

¹ Department of Materials Science, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
² Center of Radiation Processing for Polymer Modification and Nanotechnology (CRPN), Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
³ Laboratório 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.
⁴ Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65211, USA.
⁵ Department of Radiology, University of Missouri, Columbia, MO, 65211, USA.
⁶ Department of Physics, University of Missouri, Columbia, MO, 65211, USA.

Abstract

Introduction: 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; nanoradiopharmaceutical; prostate cancer; water-soluble chitosan.