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明胶基碳量子点-分子印迹聚合物:安全的光致发光核壳纳米载体,用于 pH 响应性抗癌药物输送。

Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery.

机构信息

Department of Organic Chemistry, Shahid Beheshti University, Daneshjou Boulevard, Tehran, 1983969411, Iran.

Department of Organic Chemistry, Shahid Beheshti University, Daneshjou Boulevard, Tehran, 1983969411, Iran.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 2):134669. doi: 10.1016/j.ijbiomac.2024.134669. Epub 2024 Aug 14.

Abstract

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

摘要

本研究旨在通过沉淀自由基聚合过程,以甲氨蝶呤(MTX)为模型抗癌模板,合成基于核壳明胶的碳量子点-分子印迹聚合物(MIP@g-CQD)。为了研究所制备的光致发光 MIP@g-CQD 作为 pH 响应纳米载体的效率,通过将药物溶液浸泡将 MTX 载入 MIP@g-CQD 中,并在必要的 pH 值(7.4、5)下评估载药的释放行为。使用 PL、TEM、FE-SEM、DLS 和 FT-IR 分析对材料的成功合成进行了表征。有趣的是,核壳纳米载体中的空腔可以与 MTX 分子有效相互作用,从而增加载药量。根据 Langmuir 吸附等温线获得的结果,计算了印迹因子(IF=4.91)。此外,MTX 的结合动力学揭示了在核壳聚合物网络中形成了特定的识别位点。载有 MTX 的 MIP@g-CQD 在模拟生理环境(pH 7.4,37°C)下显示出低释放率和有限释放,但在肿瘤组织(pH 5,41°C)条件下释放率增加,可导致 MTX 在目标中的长期和持续释放。MIP@g-CQD 的这种特性可以避免 MTX 在正常生理条件下的释放,减少 MTX 药物的可能副作用。由于纳米载体结构中存在酰胺官能团及其带负电荷的性质,MTX 负载的纳米载体对乳腺癌细胞系(MCF-7)的 MTT 测定显示出良好的细胞毒性。根据获得的结果,制备的具有适当 pH 响应性的安全光致发光 MIP@g-CQD 具有作为抗癌和生物检测剂的高应用能力。

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