Water-soluble chitosan conjugated DOTA-bombesin peptide capped gold nanoparticles as a targeted therapeutic agent for prostate cancer

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.