Tangthong Theeranan, Piroonpan Thananchai, Thipe Velaphi C, Khoobchandani Menka, Katti Kavita, Katti Kattesh V, Pasanphan Wanvimol
Department of Materials Science, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
Center of Radiation Processing for Polymer Modification and Nanotechnology (CRPN), Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
Nanotechnol Sci Appl. 2021 Mar 18;14:69-89. doi: 10.2147/NSA.S301942. eCollection 2021.
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.
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.
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).
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 AuNPs theragnostic nanoradiopharmaceutical for use in cancer diagnosis and therapy.
用金纳米颗粒（AuNPs）和赖氨酸-赖氨酸3（1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸）-蛙皮素1-14（DOTA-BBN）肽对水溶性壳聚糖（WSCS）纳米胶体进行功能化处理，为生产前列腺肿瘤细胞特异性纳米药物制剂提供了一条创新途径，这些制剂在分子成像和治疗方面具有潜在应用价值。
制备过程包括通过γ射线（80 kGy）辐照生产并全面表征水溶性壳聚糖（WSCS），随后进行DOTA-BBN偶联，以便后续用作合成肿瘤细胞特异性AuNPs-WSCS-DOTA-BBN的有效模板。
WSCS-DOTA-BBN聚合物纳米颗粒（86 ± 2.03 nm）在肿瘤细胞靶向AuNPs的整体模板合成中起到了还原剂和稳定剂的多种作用。用WSCS和WSCS-DOTA-BBN包覆的AuNPs的平均金核直径分别为17 ± 8 nm和20 ± 7 nm，流体动力学直径分别为56 ± 1 nm和67 ± 2 nm。AuNPs-WSCS-DOTA-BBN在生物相关溶液中表现出最佳的体外稳定性。靶向AuNPs对前列腺癌细胞（PC-3和LNCaP）中过表达的GRP受体显示出选择性亲和力。
AuNPs-WSCS-DOTA-BBN对PC-3和LNCaP癌细胞显示出细胞毒性作用，同时对人主动脉内皮细胞（HAECs）正常细胞具有安全性。AuNPs-WSCS-DOTA-BBN显示出对肿瘤细胞的协同靶向作用以及AuNPs对PC-3和LNCaP细胞的选择性细胞毒性。我们的研究提供了令人信服的证据，表明用WSCS-DOTA-BBN功能化的AuNPs是一种用于GRP受体阳性肿瘤分子成像和治疗的创新纳米医学方法。AuNPs-WSCS-DOTA-BBN的模板合成可作为开发用于癌症诊断和治疗的相应AuNPs诊断治疗纳米放射性药物的优秀非放射性替代方法。
