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通过共价功能化脂质体进行癌细胞检测与精准靶向给药

Cancer Cell Detection and Precision Targeting Drug Delivery by Covalently Functionalized Liposome.

作者信息

Ghosh Malabika, Dasgupta Uddipan, Barman Sourav, Ray Abhinibesh, Chatterjee Bama Prasanna, Chakraborty Anindita, Das Ujjal, Chakraborty Pampi, Pramanik Goutam, Maity Amit Ranjan, Dutta Chowdhury Ankan

机构信息

Amity Institute of Nanotechnology, Amity University Kolkata, Major Arterial Road, AA II, Newtown, Kolkata, West Bengal 700135, India.

Amity Institute of Biotechnology, Amity University Kolkata, Major Arterial Road, AA II, Newtown, Kolkata, West Bengal 700135, India.

出版信息

ACS Appl Bio Mater. 2025 Sep 15;8(9):8285-8296. doi: 10.1021/acsabm.5c01225. Epub 2025 Sep 2.

Abstract

In diagnostics, targeting ability is still a topic of concern for cancer cell detection as well as the drug delivery process. Selective detection of cancer cells from normal cells is a highly demanding but also crucial and challenging task. Recent emergence of folic acid as a targeting ligand can improve the drug delivery systems specifically targeted to cancer cells due to the high affinity to bind the folate receptor (FR) on the surface of cancer cells. In this study, the potential of covalently conjugated folic acid-liposomes (FA-liposomes) has been applied to detect cancer cells and thereafter for targeted drug delivery. Doxorubicin (Dox) has been used as a standard anticancer drug as well as the fluorophore probe for optical detection. To make a rigid sensor probe and nanocarrier, the amine-functionalized phospholipid modifications have been assembled for liposome formation, followed by Dox-encapsulation (FA-Lip-Dox). The targeting efficiency of FA-Lip-Dox was evaluated using three cell lines: CHO (noncancerous, control), U87MG (cancerous, low FR expression), and KB (cancerous, high FR expression) for cell detection. Additionally, for targeted drug delivery, significant Dox penetration in FR-overexpressed cancerous cells has been observed by fluorescence imaging and flow cytometry, while nontargeting cells exhibited negligible drug accumulation. This targeted delivery approach aims to maximize therapeutic efficacy in malignant cells while minimizing off-target effects and toxicity in healthy cells. The study found low cytotoxicity toward normal cells, highlighting the potential use of FA-Lip-Dox as a targeted nanocarrier for cell detection and effective drug delivery in cancer treatment.

摘要

在诊断中,靶向能力仍然是癌细胞检测以及药物递送过程中备受关注的一个话题。从正常细胞中选择性检测癌细胞是一项要求极高但又至关重要且具有挑战性的任务。叶酸作为一种靶向配体最近的出现,由于其与癌细胞表面叶酸受体(FR)具有高亲和力,能够改善专门靶向癌细胞的药物递送系统。在本研究中,共价偶联叶酸的脂质体(FA-脂质体)的潜力已被应用于检测癌细胞,进而用于靶向药物递送。阿霉素(Dox)已被用作标准抗癌药物以及用于光学检测的荧光团探针。为了制备刚性传感器探针和纳米载体,已组装胺功能化磷脂修饰物以形成脂质体,随后进行阿霉素包封(FA-Lip-Dox)。使用三种细胞系评估了FA-Lip-Dox的靶向效率:CHO(非癌细胞,对照)、U87MG(癌细胞,低FR表达)和KB(癌细胞,高FR表达)用于细胞检测。此外,对于靶向药物递送,通过荧光成像和流式细胞术观察到在FR过表达的癌细胞中有显著的阿霉素渗透,而非靶向细胞显示出可忽略不计的药物积累。这种靶向递送方法旨在使恶性细胞中的治疗效果最大化,同时将健康细胞中的脱靶效应和毒性最小化。该研究发现对正常细胞的细胞毒性较低,突出了FA-Lip-Dox作为用于细胞检测和癌症治疗中有效药物递送的靶向纳米载体的潜在用途。

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