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一种 TMVP1 修饰的近红外纳米探针:用于前哨淋巴结转移的分子成像和靶向增强光热治疗。

A TMVP1-modified near-infrared nanoprobe: molecular imaging for tumor metastasis in sentinel lymph node and targeted enhanced photothermal therapy.

机构信息

Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.

National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.

出版信息

J Nanobiotechnology. 2023 Apr 17;21(1):130. doi: 10.1186/s12951-023-01883-6.

Abstract

BACKGROUND

TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging.

RESULTS

In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine.

CONCLUSION

TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.

摘要

背景

TMVP1 是我们实验室筛选的一种新型肿瘤靶向多肽,其核心序列为五个氨基酸 LARGR。它特异性地与血管内皮生长因子受体-3(VEGFR-3)结合,VEGFR-3 主要表达于成人肿瘤转移的前哨淋巴结(SLN)中的新生淋巴管上。在这里,我们使用 TMVP1 修饰的纳米材料制备了一种靶向纳米探针,用于肿瘤转移 SLN 的成像。

结果

在这项研究中,TMVP1 修饰的聚合物纳米材料负载近红外(NIR)荧光染料吲哚菁绿(ICG),以制备分子成像 TMVP1-ICG 纳米颗粒(NPs),以在分子水平上识别 SLN 中的肿瘤转移。采用纳米沉淀法成功制备了 TMVP1-ICG-NPs。测定了其粒径、形态、药物包封率、紫外吸收光谱、细胞毒性、安全性和药代动力学特性。TMVP1-ICG-NPs 的粒径约为 130nm,ICG 包封率为 70%。体外细胞实验和体内小鼠实验证实,TMVP1-ICG-NPs 通过与 VEGFR-3 结合,对原位肿瘤和有肿瘤转移的 SLN 具有良好的靶向能力。体外和体内实验证实了 TMVP1-ICG-NPs 具有有效的光热治疗(PTT)效果。正如预期的那样,TMVP1-ICG-NPs 提高了 ICG 的血液稳定性,靶向肿瘤转移到 SLN,并增强了 PTT/光动力(PDT)治疗,同时没有明显的细胞毒性,使其成为一种有前途的治疗性纳米医学。

结论

TMVP1-ICG-NPs 可识别有肿瘤转移的 SLN,并用于进行成像引导的 PTT,为 SLN 转移患者提供实时 NIR 荧光成像和术中 PTT 提供了一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447c/10108508/c7a2b703dad0/12951_2023_1883_Sch1_HTML.jpg

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