用于肿瘤靶向多柔比星递送和成像的细胞穿透肽 GRP78 配体偶联氧化铁磁性纳米颗粒,ACS Applied Bio Materials

当前位置： X-MOL 学术 › ACS Appl. Bio Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

用于肿瘤靶向多柔比星递送和成像的细胞穿透肽 GRP78 配体偶联氧化铁磁性纳米颗粒
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2023-03-02 , DOI: 10.1021/acsabm.2c00897
Mahdiyeh Hasani ₁ , Samira Jafari ₂ , Hamid Akbari Javar ₃ , Hossein Abdollahi ₄ , Hamid Rashidzadeh _{1,

5}

Affiliation

尽管化学疗法被视为癌症治疗中必不可少的选择，但它仍远非完美。肿瘤药物浓度不足和全身毒性以及广泛的生物分布已经削弱了化学疗法的效用。肿瘤靶向肽缀合的多功能纳米平台已成为癌症治疗和成像中定点肿瘤组织的有效策略。在此，成功开发了Pep42 靶向氧化铁磁性纳米粒子 (IONPs)，该纳米粒子用含有多柔比星 (DOX) 的 β-环糊精 (ßCD) 功能化 (Fe ₃ O _{4 -ßCD-Pep42-DOX)。}所制备的 NP 的物理效应通过采用各种技术进行表征。透射电子显微镜 (TEM) 图像显示，开发的 Fe ₃O ₄ -ßCD-Pep42-DOX纳米平台具有球形形态和核壳结构，尺寸接近17 nm。傅立叶变换红外 (FT-IR) 光谱表明，β-环糊精、DOX 和 Pep42 分子已成功加载到 IONP 上。体外细胞毒性分析表明，制备的多功能 Fe ₃ O ₄ -ßCD-Pep42 纳米平台对 BT-474、MDA-MB468（癌细胞）和 MCF10A 正常细胞具有优异的生物安全性，而 Fe ₃ O ₄ -ßCD-Pep42-DOX表现出很强的癌细胞杀伤能力。高细胞摄取以及 Fe ₃ O _{4的细胞内运输}-ßCD-Pep42-DOX 突出了 Pep42 靶向肽的实用性。体内结果强烈支持体外结果，即通过将 Fe ₃ O ₄ -ßCD-Pep42-DOX单剂量注射到荷瘤小鼠中，观察到肿瘤大小显着减小。有趣的是， Fe ₃ O ₄ -ßCD-Pep42-DOX的体内MR 成像 (MRI)揭示了肿瘤细胞的T _{2对比改善和癌症治疗的治疗能力。}总之，这些发现为 Fe ₃ O _{4的潜在能力提供了强有力的证据}-ßCD-Pep42-DOX 作为癌症治疗和成像的多功能纳米平台，开辟了该领域的新研究途径。

"点击查看英文标题和摘要"

Cell-Penetrating Peptidic GRP78 Ligand-Conjugated Iron Oxide Magnetic Nanoparticles for Tumor-Targeted Doxorubicin Delivery and Imaging

Although chemotherapy is regarded as an essential option in cancer treatment, it is still far from being perfect. Inadequate tumor drug concentration and systemic toxicity along with broad biodistribution have diminished the utility of chemotherapy. Tumor-targeting peptide-conjugated multifunctional nanoplatforms have emerged as an effective strategy for site-directed tumor tissues in cancer treatment and imaging. Herein, Pep42-targeted iron oxide magnetic nanoparticles (IONPs) functionalized with β-cyclodextrin (ßCD) containing doxorubicin (DOX) (Fe₃O₄-ßCD-Pep42-DOX) were successfully developed. The physical effects of the prepared NPs were characterized by employing various techniques. Transmission electron microscopy (TEM) images disclosed that the developed Fe₃O₄-ßCD-Pep42-DOX nanoplatforms had a spherical morphology and a core–shell structure with a size of nearly 17 nm. Fourier transform infrared (FT-IR) spectroscopy showed that β-cyclodextrin, DOX, and Pep42 molecules were successfully loaded on the IONPs. In vitro cytotoxicity analysis revealed that the fabricated multifunctional Fe₃O₄-ßCD-Pep42 nanoplatforms possessed excellent biosafety toward BT-474, MDA-MB468 (cancerous cells), and MCF10A normal cells, while Fe₃O₄-ßCD-Pep42-DOX exhibited great cancer cell killing ability. The high cellular uptake along with intracellular trafficking of Fe₃O₄-ßCD-Pep42-DOX highlights the usefulness of the Pep42-targeting peptide. In vivo results strongly supported the in vitro results, i.e., significant tumor size reduction was observed by single-dose injection of Fe₃O₄-ßCD-Pep42-DOX into tumor-bearing mice. Interestingly, in vivo MR imaging (MRI) of Fe₃O₄-ßCD-Pep42-DOX revealed T₂ contrast improvement in the tumor cells and therapeutic ability in cancer theranostics. Taken together, these findings provided strong evidence for the potential capability of Fe₃O₄-ßCD-Pep42-DOX as a multifunctional nanoplatform in cancer therapy and imaging and opens up a new avenue of research in this area.

更新日期：2023-03-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>