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蛙皮素肽偶联水溶性壳聚糖没食子酸酯 - 一种用于快速一锅法合成前列腺肿瘤靶向金纳米粒子的新型纳米药物制剂。

Bombesin Peptide Conjugated Water-Soluble Chitosan Gallate-A New Nanopharmaceutical Architecture for the Rapid One-Pot Synthesis of Prostate Tumor Targeted Gold Nanoparticles.

机构信息

Department of Materials Science, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.

Center of Radiation Processing for Polymer Modification and Nanotechnology (CRPN), Department of Materials Science, Faculty of Science, Kasetsart University Chatuchak, Bangkok, 10900, Thailand.

出版信息

Int J Nanomedicine. 2021 Oct 13;16:6957-6981. doi: 10.2147/IJN.S327045. eCollection 2021.

Abstract

PURPOSE

We report herein bombesin peptide conjugated water-soluble chitosan gallate as a template for rapid one-pot synthesis of gold nanoparticles (AuNPs) with capabilities to target receptors on prostate cancer cells.

METHODS

Water-soluble chitosan (WCS), anchored with gallic acid (GA) and LyslLys3 (1,4,7,10-tetraazacyclo dodecane-1,4,7,10-tetraacetic acid) bombesin 1-14 (DBBN) peptide, provides a tumor targeting nanomedicine agent. WCS nanoplatforms provide attractive strategies with built-in capabilities to reduce gold (III) to gold nanoparticles with stabilizing and tumor-targeting capabilities. WCS-GA-DBBN encapsulation around gold nanoparticles affords optimum in vitro stability.

RESULTS

The DBBN content in the WCS-GA-DBBN sample was ~27%w/w. The antioxidant activities of WCS-GA and WCS-GA-DBBN nanocolloids were enhanced by 12 times as compared to the nascent WCS. AuNPs with a desirable hydrodynamic diameter range of 40-60 nm have been efficiently synthesized using WCS-GA and WCS-GA-DBBN platforms. The AuNPs were stable over 4 days after preparation and ~3 days after subjecting to all relevant biological fluids. The AuNPs capped with WCS-GA-DBBN peptide exhibited superior cellular internalization into prostate tumor (PC-3) cells with evidence of receptor mediated endocytosis.

CONCLUSION

The AuNPs capped with WCS-GA-DBBN exhibited selective affinity toward prostate cancer cells. AuNPs conjugated with WCS-GA-DBBN serve as a new generation of theranostic agents for treating various neoplastic diseases, thus opening-up new applications in oncology.

摘要

目的

我们在此报告一种将蛙皮素肽与水溶性壳聚糖没食子酸缀合作为模板,用于快速一锅法合成具有靶向前列腺癌细胞受体能力的金纳米粒子(AuNPs)。

方法

水溶性壳聚糖(WCS)与没食子酸(GA)和 LyslLys3(1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸)蛙皮素 1-14(DBBN)肽结合,提供了一种肿瘤靶向纳米药物。WCS 纳米平台提供了具有内在能力的有吸引力的策略,可将金(III)还原为具有稳定和肿瘤靶向能力的金纳米粒子。WCS-GA-DBBN 封装在金纳米粒子周围,可提供最佳的体外稳定性。

结果

WCS-GA-DBBN 样品中的 DBBN 含量约为 27%w/w。与新生的 WCS 相比,WCS-GA 和 WCS-GA-DBBN 纳米胶体的抗氧化活性提高了 12 倍。使用 WCS-GA 和 WCS-GA-DBBN 平台,高效合成了具有理想水动力直径范围为 40-60nm 的 AuNPs。AuNPs 在制备后 4 天和经受所有相关生物流体后 3 天内保持稳定。用 WCS-GA-DBBN 肽封端的 AuNPs 表现出对前列腺肿瘤(PC-3)细胞的优越细胞内化能力,并证明了受体介导的内吞作用。

结论

用 WCS-GA-DBBN 封端的 AuNPs 对前列腺癌细胞表现出选择性亲和力。用 WCS-GA-DBBN 缀合的 AuNPs 作为治疗各种肿瘤疾病的新一代治疗诊断试剂,从而为肿瘤学开辟了新的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a288/8520890/49479f5338d3/IJN-16-6957-g0001.jpg

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