Department of Chemistry, Indian Institute of Science Education and Research (IISER Pune), Dr Homi Bhabha Road, Pune 411008, Maharashtra, India.
Laboratory of Neural Circuits and Behaviour (LNCB), Department of Biology, Indian Institute of Science Education and Research (IISER Pune), Dr Homi Bhabha Road, Pune 411008, Maharashtra, India.
Nanoscale. 2024 Nov 28;16(46):21582-21593. doi: 10.1039/d4nr02636e.
Nanocarrier-mediated therapeutic delivery to brain tissue is impeded by tightly controlled transportation across the blood-brain barrier (BBB). Herein, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM; a single polymer entity) as an efficient BBB-breaching nanoparticle for brain-specific administration of the fluorescent anticancer drug doxorubicin and mapping of brain tissues by the near-infrared biomarker IR780 in mice. The star-UMM was engineered by precisely programming the polymer topology having hydrophobic and hydrophilic polycaprolactone blocks and in-built with lysosomal enzyme-biodegradation stimuli to deliver the payloads at intracellular compartments. imaging in mice revealed prolonged circulation of star-UMM in blood for >72 h, and whole-organ image-quantification substantiated its efficient ability to breach the BBB. Star UMM exhibited excellent stability in blood circulation and reduced cardiotoxicity, was non-hemolytic, had substantial uptake in the cortical neurons of the mouse brain, had lysosomal enzymatic-biodegradation, and exhibited negligible immunogenicity or necrosis. This newly designed star-UMM could have long-term applications in brain-specific drug delivery.
纳米载体介导的脑内治疗输送受到血脑屏障 (BBB) 严格控制的跨膜转运的阻碍。在此，我们报告了一种结构明确的核壳星形单分子胶束 (星形 UMM；单一聚合物实体)，它是一种有效的 BBB 破坏纳米颗粒，可用于将荧光抗癌药物阿霉素脑内特异性给药，并通过近红外生物标记物 IR780 在小鼠中对脑组织进行成像。星形 UMM 通过精确编程聚合物拓扑结构来设计，具有疏水性和亲水性聚己内酯嵌段，并内置溶酶体酶降解刺激，以将有效载荷递送至细胞内隔室。在小鼠中的成像研究表明，星形 UMM 在血液中的循环时间超过 72 h，全器官图像定量证实了其有效穿透 BBB 的能力。星形 UMM 在血液循环中表现出优异的稳定性和降低的心脏毒性，非溶血，在小鼠大脑的皮质神经元中有大量摄取，具有溶酶体酶降解作用，并且表现出可忽略不计的免疫原性或坏死作用。这种新设计的星形 UMM 可能在脑内特异性药物输送方面具有长期应用前景。
