Optimizing long-term stability of siRNA using thermoassemble ionizable reverse pluronic-Bcl2 micelleplexes

• Published in: International journal of biological macromolecules Vol. 264; no. Pt 2; p. 130783
• Main Authors: De, Anindita, Kang, Ji Hee, Sauraj, Lee, O Hyun, Ko, Young Tag
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2024
• Subjects: Bcl2 siRNA; Blood brain barrier crossing; blood-brain barrier; Cell Line, Tumor; fever; Gene Silencing; genes; glioblastoma; Glioblastoma - metabolism; Humans; Ionizable reverse pluronic; Long-term stability; Micelles; nanocarriers; Nanoparticles - chemistry; particle size; Poloxamer - chemistry; RNA, Small Interfering - chemistry; Thermosassemble; Tumor Microenvironment; Thermosassemble; Ionizable reverse pluronic; Bcl2 siRNA; Blood brain barrier crossing; Long-term stability
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.130783

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. [Display omitted] •TIRP tech tackles siRNA hurdles with thermoassembly & ionizable characteristics overcoming past limitations.•TIRP-Bcl2's flexi-rigid response to hyperthermia boosts tissue penetration, siRNA release, and gene silencing in cancer.•Dual ionizable headgroup boosts siRNA loading; while reverse pluronic's unique orientation stabilizes encapsulated siRNA.