研究进展 情报发生 2026-10-31 · 发布于 2026-11-01

工程化天然膜囊泡外泌体递送 Torin2:靶向治疗甲状腺未分化癌

来源:Int J Nanomedicine · PMID 42948446 · DOI 10.2147/ijn.s633252 · 来源:IMA 知识库《文献层·文献监控卡片》2026-10-31 期 · 全文级(file_id dmlmcfQeUyzO,实际下载核验) · 全文已获取并通过归属校验

时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31

研究问题

The iRGD peptide (CRGDKGPDC) was selected for its unique tumor-penetrating properties: unlike conventional RGD peptides that only bind to integrins αvβ3 on tumor vasculature, iRGD undergoes proteolytic cleavage to expose a C-end Rule (CendR) motif that binds neuropilin-1, enabling active transcellular penetration into the tumor parenchyma., Leveraging this receptor not only facilitates selective drug delivery to the tumor microenvironment but also enables the design of ligand-modified nanocarriers with enhanced tumor-penetrating capabilities, thereby addressing the dual challenges of poor target specificity and insufficient intratumoral drug distribution.;However, native exosomes display limited intrinsic tropism toward tumor tissue, which restricts their clinical utility in tumor-targeted therapy.

方法

Given the retrospective nature of this study and the extended archival period of over ten years for the specimens, during which some patients had deceased, the requirement for individual informed consent was waived by the overseeing ethics committee.;The study protocol was reviewed and approved by the Institutional Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No.;Paraffin-embedded tissue sections from matched pairs of ATC tissues and adjacent non-neoplastic thyroid tissues were subjected to immunohistochemical staining using a rabbit polyclonal anti-integrin αvβ3 antibody (bs-1310R, Bioss, China) at a working dilution of 1:200, according to the manufacturer’s instructions.;These lentiviral expression vectors were used to transduce HEK-293T cells, followed by a 48-hour incubation.

核心结论

The iRGD peptide mediates tumor-selective extravasation and penetration by binding to integrin αvβ3 or αvβ5, which are often overexpressed on tumor vasculature and cancer cells.,, To assess the feasibility of iRGD peptide-based targeting in ATC, we first evaluated the expression of its cognate receptors, integrin αvβ3.;Immunohistochemical analysis of 10 matched ATC patient tissue pairs revealed substantially higher expression levels of integrin αvβ3 in malignant tissues compared to their adjacent noncancerous counterparts ().;Thus, we identified ATC as a viable candidate for iRGD peptide therapeutic strategies. ‖ 结论:We believe these findings constitute a substantial advancement over our prior work and offer a promising strategy for integrin αvβ3-overexpressing malignancies.

局限

Nevertheless, the long-term safety of repeated dosing and the potential effects of exosomal components on hepatic function warrant further investigation.;Third, although the liver showed substantial exosome uptake, the drug may be sequestered within endosomal/lysosomal compartments of Kupffer cells and hepatocytes, limiting its availability to exert cytotoxic effects on hepatocytes.;To explore these mechanisms, future studies should include comprehensive pharmacokinetic and biodistribution analyses using LC-MS/MS to quantify Torin2 levels in plasma, tumor, liver, kidney, and other major organs over time; investigation of the cellular uptake of Torin2@iRGD-Exos by different liver cell populat

对本项目的价值

★☆☆☆☆ 代谢轴既干预敏感性最高,也是老药新用供给最充足的来源。

全文来源

PMC JATS 全文(正文 39,622 字符,已过标题/DOI 逐字归属校验)

原文题录

  • 英文标题:Engineered Natural Membrane Vesicle Exosomes as a Torin2 Delivery Platform for Targeted Therapy of Anaplastic Thyroid Carcinoma.
  • 期刊与标识:Int J Nanomedicine · PMID 42948446 · DOI 10.2147/ijn.s633252

A 级证据分级:A 级(同行评议人体研究)

本文属人体研究证据,但需注意:观察性或小样本干预的结论不等于已证实临床获益;效应量与长期安全性仍需更大规模、更长随访的试验验证。

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