College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, South Korea..
College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, South Korea.
Int J Biol Macromol. 2024 Apr;264(Pt 2):130783. doi: 10.1016/j.ijbiomac.2024.130783. Epub 2024 Mar 11.
Thermosassemble Ionizable Reverse Pluronic (TIRP) platform stands out for its distinctive combination of thermoassemble and ionizable features, effectively overcoming challenges in previous siRNA delivery systems. This study opens up a formation for long-term stabilization, and high loading of siRNA, specifically crafted for targeting oncogenic pathways. TIRP-Bcl2 self-assembles into a unique micelle structure with a nanodiameter of 75.8 ± 5.7 nm, efficiently encapsulating Bcl2 siRNA while maintaining exceptional colloidal stability at 4 °C for 8 months, along with controlled release profiles lasting 180 h. The dual ionizable headgroup enhance the siRNA loading and the revers pluronic unique structural orientation enhance the stability of the siRNA. The thermoassemble of TIRP-Bcl2 facilitates flexi-rigid response to mild hyperthermia, enhancing deep tissue penetration and siRNA release in the tumor microenvironment. This responsive behavior improves intracellular uptake and gene silencing efficacy in cancer cells. TIRP, with its smaller particle size and reverse pluronic nature, efficiently transports siRNA across the blood-brain barrier, holding promise for revolutionizing glioblastoma (GBM) treatment. TIRP-Bcl2 shows significant potential for precise, personalized therapies, promising prolonged siRNA delivery and in vitro/in vivo stability. This research opens avenues for further exploration and clinical translation of this innovative nanocarrier system across different cancers.
Thermosassemble Ionizable Reverse Pluronic (TIRP) 平台以其独特的热组装和可离子化特性脱颖而出，有效地克服了以前 siRNA 递药系统的挑战。这项研究为长期稳定和高负载 siRNA 的形成开辟了道路，特别针对致癌途径进行了设计。TIRP-Bcl2 自组装成一种独特的胶束结构，纳米直径为 75.8±5.7nm，有效地包裹 Bcl2 siRNA，同时在 4°C 下保持卓越的胶体稳定性长达 8 个月，并具有长达 180h 的控制释放曲线。双离子化头基增强了 siRNA 的负载，而可逆 pluronic 独特的结构取向增强了 siRNA 的稳定性。TIRP-Bcl2 的热组装促进了对温和热疗的灵活刚性响应，增强了在肿瘤微环境中的深层组织穿透和 siRNA 释放。这种响应行为提高了癌细胞内的摄取和基因沉默效果。TIRP 具有较小的粒径和反向 pluronic 性质，能够有效地将 siRNA 穿过血脑屏障，有望彻底改变胶质母细胞瘤（GBM）的治疗方法。TIRP-Bcl2 显示出在精确、个性化治疗方面的巨大潜力，有望延长 siRNA 的递药时间和体外/体内稳定性。这项研究为进一步探索和临床转化这种创新的纳米载体系统在不同癌症中的应用开辟了道路。
