水溶性壳聚糖偶联DOTA-Bombesin肽包覆金纳米颗粒作为前列腺癌靶向治疗剂。

IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY
Nanotechnology, Science and Applications Pub Date : 2021-03-18 eCollection Date: 2021-01-01 DOI:10.2147/NSA.S301942
Theeranan Tangthong, Thananchai Piroonpan, Velaphi C Thipe, Menka Khoobchandani, Kavita Katti, Kattesh V Katti, Wanvimol Pasanphan
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引用次数: 16

摘要

摘要:水溶性壳聚糖(WSCS)纳米胶体与金纳米粒子(AuNPs)和LyslLys3(1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸)-bombesin 1-14 (DOTA-BBN)肽的功能化为生产前列腺肿瘤细胞特异性纳米药物提供了一条创新途径,在分子成像和治疗方面具有潜在的应用前景。方法:通过γ (γ)射线(80 kGy)照射制备水溶性壳聚糖(WSCS)并对其进行全面表征,随后将DOTA-BBN偶联,作为合成肿瘤细胞特异性AuNPs-WSCS-DOTA-BBN的有效模板。结果:WSCS-DOTA-BBN纳米聚合物(86±2.03 nm)在肿瘤细胞靶向AuNPs的整体模板合成中具有还原和稳定作用。经WSCS和WSCS- dota - bbn封顶的AuNPs平均au核直径分别为17±8 nm和20±7 nm,水动力直径分别为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对前列腺癌细胞中过表达的GRP受体(PC-3和LNCaP)具有选择性亲和力。讨论:AuNPs-WSCS-DOTA-BBN对PC-3和LNCaP癌细胞显示细胞毒性作用,同时对HAECs正常细胞具有安全性。AuNPs- wscs - dota - bbn对肿瘤细胞具有协同靶向作用,对PC-3和LNCaP细胞具有选择性细胞毒性。我们的研究提供了令人信服的证据,证明WSCS-DOTA-BBN功能化的AuNPs是一种创新的纳米医学方法,可用于GRP受体阳性肿瘤的分子成像和治疗。通过模板合成AuNPs-WSCS-DOTA-BBN,为开发相应的用于癌症诊断和治疗的198AuNPs诊断性纳米放射药物提供了良好的非放射性替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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

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

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.

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来源期刊
Nanotechnology, Science and Applications
Nanotechnology, Science and Applications NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
11.70
自引率
0.00%
发文量
3
审稿时长
16 weeks
期刊介绍: Nanotechnology, Science and Applications is an international, peer-reviewed, Open Access journal that focuses on the science of nanotechnology in a wide range of industrial and academic applications. The journal is characterized by the rapid reporting of reviews, original research, and application studies across all sectors, including engineering, optics, bio-medicine, cosmetics, textiles, resource sustainability and science. Applied research into nano-materials, particles, nano-structures and fabrication, diagnostics and analytics, drug delivery and toxicology constitute the primary direction of the journal.
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