Albumin-stabilized manganese-based nanocomposites with sensitive tumor microenvironment responsivity and their application for efficient SiRNA delivery in brain tumors

纳米复合材料 响应度 癌症研究 化学 白蛋白 脑瘤 材料科学 纳米技术 医学 病理 光电子学 生物化学 光电探测器 有机化学
作者
Kai Xu,Zhenghuan Zhao,Junfeng Zhang,Wei Xue,Haipeng Tong,Heng Liu,Weiguo Zhang
出处
期刊:Journal of Materials Chemistry B [Royal Society of Chemistry]
卷期号:8 (7): 1507-1515 被引量:25
标识
DOI:10.1039/c9tb02341k
摘要

Mn(iv)-Based nanoparticles (NPs) are effective in improving tumor oxygenation (hypoxia) and reducing endogenous hydrogen peroxide and acidity in the tumor region. However, the optimized reduction conditions of conventional Mn(iv)-based NPs are generally reported at pH ≤ 6.5, while the usual pH range of the tumor microenvironment (TME) is 6.5-7.0. The dissatisfactory imaging performance in the weakly acidic environment may limit their further application in tumor diagnosis. In this study, Mn(iii) was introduced in a nanoplatform, because it is reduced into Mn(ii) in weakly acidic environments. Arg-Gly-Asp (RGD) peptide-decorated bovine serum albumin (BSA) was employed as the stabilizer and scaffold to fabricate Mn(iii)- and Mn(iv)-integrated nanocomposites (RGD-BMnNPs) with suitable size, good stability, and excellent biocompatibility. The as-prepared NPs showed clear contrast enhancement at pH 6.5-6.9 in vitro as well as sensitive and rapid T1-weighted imaging performance within the tumor region in a glioblastoma (U87MG) orthotopic model, owing to the intrinsic disproportionation reaction of Mn(iii) in the weakly acidic environment. In addition, these NPs could be used for efficient siRNA delivery. They showed superior advantages in this process, including increased tumour uptake, improved tumor accumulation and enhanced therapeutic effects with the modulation of the TME. These novel albumin-stabilized manganese-based NPs combined with efficient drug delivery capacity hold great potential to serve as intelligent theranostic agents for further clinical translation.
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