期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 180, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejps.2022.106336
关键词
Gallium-68; DOTA; Virus-like particle; Hepatitis E viral nanoparticles; LXY30; HCT 116 colorectal cancer cells
Integrins are cell surface receptors that play important roles in cellular functions. This study explores the overexpression of α13-integrins in tumor cells, making them potential biomarkers for diagnostic imaging and tumor-targeted drug delivery. The research focuses on the evaluation of HEVNPs as drug delivery agents, and the conjugation of LXY30 peptide to enhance the binding and internalization of HEVNPs to α3131 integrin expressing cells.
Integrins are cell surface receptors involved in multiple functions vital for cellular proliferation. Various tumor cells overexpress & alpha;13-integrins, making them ideal biomarkers for diagnostic imaging and tumor-targeted drug delivery. LXY30 is a peptide that can specifically recognize and interact with the integrin & alpha;3131, a molecule overexpressed in breast, ovarian and colorectal cancer. Hepatitis E virus nanoparticles (HEVNPs) are virus-like particles that have been investigated as drug delivery agents for the targeted delivery of nucleic acids and small proteins. HEVNPs can be a theranostic platform for monitoring and evaluating tumor-targeted therapies if tagged with a suitable diagnostic marker. Herein, we describe the radiolabeling and biological evaluation of integrin & alpha;3131-targeted HEVNPs. HEVNPs were conjugated with DOTA and radiolabeled with gallium-68 (t1/2 = 67.7 min), a short-lived positron emitter used in positron emission tomography (PET). The synthesized [68Ga]GaDOTA-HEVNPs were used to evaluate the efficacy of conjugated LXY30 peptide to improve HEVNPs binding and internalization to integrin & alpha;3131 expressing human colorectal HCT 116 cells. In vivo tumor accumulation of [68Ga] Ga-DOTA-HEVNP-LXY30 was evaluated in HCT 116 colorectal tumor-bearing mice. [68Ga]Ga-DOTA-HEVNPLXY30 and non-targeted [68Ga]Ga-DOTA-HEVNP were radiolabeled with radiochemical yields (RCY) of 67.9 & PLUSMN; 3.3% and 73.7 & PLUSMN; 9.8%, respectively. [68Ga]Ga-DOTA-HEVNP-LXY30 exhibited significantly higher internalization in HCT 116 cells than the non-targeted [68Ga]Ga-DOTA-HEVNPs (21.0 & PLUSMN; 0.7% vs. 10.5 & PLUSMN; 0.3% at 3 h, ****P<0.0001). After intravenous administration to mice, accumulation of [68Ga]Ga-DOTA-HEVNP-LXY30 to HCT 116 xenograft tumors was at its highest rate of 0.8 & PLUSMN; 0.4%ID/g at 60 min. [68Ga]Ga-DOTA-HEVNP-LXY30 accumulated mainly in the liver and spleen (39.8 & PLUSMN; 13.0%%ID/g and 24.6 & PLUSMN; 24.1%ID/g, respectively). Despite the low targeting efficiency in vivo, we demonstrated that [68Ga]Ga-DOTA-HEVNP is a promising diagnostic platform for quantitative analysis of HEVNP distribution in vivo. This nanosystem can be utilized in future studies assessing the success of further engineered HEVNP structures with optimized targeting efficiency in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据