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在原位小鼠模型中,用负载上转换纳米颗粒和替莫唑胺的3D支架增强胶质瘤治疗

Enhancing glioma treatment with 3D scaffolds laden with upconversion nanoparticles and temozolomide in orthotopic mouse model.

作者信息

Mishchenko Tatiana A, Klimenko Maria O, Guryev Evgenii L, Savelyev Alexander G, Krysko Dmitri V, Gudkov Sergey V, Khaydukov Evgeny V, Zvyagin Andrei V, Vedunova Maria V

机构信息

Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.

Laboratory of Laser Biomedicine, NRC "Kurchatov Institute", Moscow, Russia.

出版信息

Front Chem. 2024 Oct 21;12:1445664. doi: 10.3389/fchem.2024.1445664. eCollection 2024.

Abstract

Targeted drug delivery for primary brain tumors, particularly gliomas, is currently a promising approach to reduce patient relapse rates. The use of substitutable scaffolds, which enable the sustained release of clinically relevant doses of anticancer medications, offers the potential to decrease the toxic burden on the patient's organism while also enhancing their quality of life and overall survival. Upconversion nanoparticles (UCNPs) are being actively explored as promising agents for detection and monitoring of tumor growth, and as therapeutic agents that can provide isolated therapeutic effects and enhance standard chemotherapy. Our study is focused on the feasibility of constructing scaffolds using methacrylated hyaluronic acid with additional impregnation of UCNPs and the chemotherapeutic drug temozolomide (TMZ) for glioma treatment. The designed scaffolds have been demonstrated their efficacy as a drug and UCNPs delivery system for gliomas. Using the aggressive orthotopic glioma model , it was found that the scaffolds possess the capacity to ameliorate neurological disorders in mice. Moreover, upon intracranial co-implantation of the scaffolds and glioma cells, the constructs disintegrate into distinct segments, augmenting the release of UCNPs into the surrounding tissue and concurrently reducing postoperative damage to brain tissue. The use of TMZ in the scaffold composition contributed to restraining glioma development and the reduction of tumor invasiveness. Our findings unveil promising prospects for the application of photopolymerizable biocompatible scaffolds in the realm of neuro-oncology.

摘要

针对原发性脑肿瘤,尤其是胶质瘤的靶向药物递送,目前是一种有望降低患者复发率的方法。使用可替代支架能够持续释放临床相关剂量的抗癌药物,这有可能减轻患者机体的毒性负担,同时提高他们的生活质量和总体生存率。上转换纳米颗粒(UCNPs)正被积极探索作为检测和监测肿瘤生长的有前景的试剂,以及作为能够提供单独治疗效果并增强标准化化疗的治疗剂。我们的研究重点是使用甲基丙烯酸化透明质酸构建支架,并额外浸渍UCNPs和化疗药物替莫唑胺(TMZ)用于治疗胶质瘤的可行性。所设计的支架已证明其作为胶质瘤的药物和UCNPs递送系统的功效。使用侵袭性原位胶质瘤模型,发现该支架具有改善小鼠神经功能障碍的能力。此外,在将支架与胶质瘤细胞颅内共植入后,构建体分解成不同片段,增加UCNPs向周围组织的释放,同时减少术后对脑组织的损伤。在支架组合物中使用TMZ有助于抑制胶质瘤的发展并降低肿瘤侵袭性。我们的研究结果揭示了可光聚合生物相容性支架在神经肿瘤学领域应用的广阔前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f684/11532134/0f8bd118da27/fchem-12-1445664-g001.jpg

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