双修饰新型仿生纳米载体改善脑胶质瘤靶向和治疗效果。

Dual-Modified Novel Biomimetic Nanocarriers Improve Targeting and Therapeutic Efficacy in Glioma.

机构信息

State Key Laboratory of Toxicology and Medical Countermeasures , Beijing Institute of Pharmacology and Toxicology , Beijing 100850 , China.

Jiamusi University , Jiamusi 154002 , China.

出版信息

ACS Appl Mater Interfaces. 2019 Jan 16;11(2):1841-1854. doi: 10.1021/acsami.8b18664. Epub 2019 Jan 4.

Abstract

Glioma is a fatal disease with limited treatment options and very short survival. Although chemotherapy is one of the most important strategies in glioma treatment, it remains extremely clinically challenging largely due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Thus, the development of nanoparticles with both BBB and BBTB penetrability, as well as glioma-targeting feature, is extremely important for the therapy of glioma. New findings in nanomedicine are promoting the development of novel biomaterials. Herein, we designed a red blood cell membrane-coated solid lipid nanoparticle (RBCSLN)-based nanocarrier dual-modified with T7 and NGR peptide (T7/NGR-RBCSLNs) to accomplish these objectives. As a new kind of biomimetic nanovessels, RBCSLNs preserve the complex biological functions of natural cell membranes while possessing physicochemical properties that are needed for efficient drug delivery. T7 is a ligand of transferrin receptors with seven peptides that is able to circumvent the BBB and target to glioma. NGR is a peptide ligand of CD13 that is overexpressed during angiogenesis, representing an excellent glioma-homing property. After encapsulating vinca alkaloid vincristine as the model drug, T7/NGR-RBCSLNs exhibited the most favorable antiglioma effects in vitro and in vivo by combining the dual-targeting delivery effect. The results demonstrate that dual-modified biomimetic nanoparticles provide a potential method to improve drug delivery to the brain, hence increasing glioma therapy efficacy.

摘要

神经胶质瘤是一种致命疾病,治疗选择有限,患者生存时间极短。尽管化疗是神经胶质瘤治疗中最重要的策略之一,但由于血脑屏障 (BBB) 和血脑肿瘤屏障 (BBTB) 的存在,它在临床上仍然极具挑战性。因此,开发具有 BBB 和 BBTB 穿透性以及神经胶质瘤靶向性的纳米颗粒对于神经胶质瘤的治疗至关重要。纳米医学的新发现正在推动新型生物材料的发展。在此,我们设计了一种红细胞膜包覆的固体脂质纳米颗粒(RBCSLN)基纳米载体,该载体同时修饰了 T7 和 NGR 肽(T7/NGR-RBCSLNs),以实现这些目标。作为一种新型仿生纳米容器,RBCSLN 保留了天然细胞膜的复杂生物学功能,同时具有高效药物递送所需的物理化学性质。T7 是转铁蛋白受体的配体,具有能够绕过 BBB 并靶向神经胶质瘤的七个肽。NGR 是一种在血管生成过程中过度表达的 CD13 肽配体,具有出色的神经胶质瘤归巢特性。将长春碱类药物长春新碱包封作为模型药物后,T7/NGR-RBCSLNs 通过双重靶向递药作用表现出最有利的体外和体内抗神经胶质瘤效果。结果表明,双重修饰仿生纳米颗粒为提高药物向大脑的递送提供了一种潜在方法,从而提高神经胶质瘤的治疗效果。

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