期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 82, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jddst.2023.104381
关键词
Gold nanoparticles; Targeted delivery; Somatostatin receptor 2; Lanreotide peptide; Radiosensitization
The aim of this study was to functionalize gold nanoparticles with Lanreotide peptide (LP) to promote their selective delivery in SSTR2-expressing cancer cells and enhance radiosensitization. The LP was coupled with negatively charged citrate-stabilized gold nanoparticles (GNP) through electrostatic interaction. The GNP-LP conjugates showed higher cellular uptake and toxicity in SSTR2-expressing AR42J cells, resulting in enhanced radiosensitization.
Lanreotide peptide (LP), a somatostatin analog with high affinity towards somatostatin receptor 2 (SSTR2) is commonly used in the treatment of neuroendocrine tumors (NETs). The aim of this study is to functionalize gold nanoparticles with LP to promote their selective delivery in SSTR2-expressing cancer cells and enhancement of radiosensitization. The negatively charged citrate-stabilized gold nanoparticles (GNP) were prepared by soft -chemical approach and coupled with positively charged LP through electrostatic interaction. The structural and kinetic properties these LP functionalized GNP (GNP-LP) were studied using various analytical techniques. The formation of appropriately sized and colloidally stable GNP-LP conjugates were evident from transmission electron microscopy and light scattering analyses. In order to investigate the targeting ability of these conjugates, cellular uptake and cytotoxicity studies were performed in AR42J cells (high SSTR2 receptors) and CHO cells (low SSTR2 receptors). It has been found that the GNP-LP conjugates exhibited higher cellular uptake in SSTR2-expressing AR42J cells over CHO cells. Thus, GNP-LP conjugates on gamma ray irradiation exhibited higher toxicity towards AR42J cells due to enhanced radiosensitization. Specifically, the present study demonstrated functionalization of GNP with LP, and their selective delivery and enhanced radiosensitization in SSTR2 over -expressing cancer cells.
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