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

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...

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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
Online Access	Get full text
ISSN	0141-8130 1879-0003 1879-0003
DOI	10.1016/j.ijbiomac.2024.130783

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Abstract	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.
AbstractList	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) 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. 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) 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) 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.
ArticleNumber	130783
Author	Kang, Ji Hee De, Anindita Sauraj Lee, O Hyun Ko, Young Tag
Author_xml	– sequence: 1 givenname: Anindita surname: De fullname: De, Anindita email: aninditanirupa@gmail.com – sequence: 2 givenname: Ji Hee surname: Kang fullname: Kang, Ji Hee – sequence: 3 surname: Sauraj fullname: Sauraj – sequence: 4 givenname: O Hyun surname: Lee fullname: Lee, O Hyun – sequence: 5 givenname: Young Tag surname: Ko fullname: Ko, Young Tag email: youngtakko@gachon.ac.kr
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CitedBy_id	crossref_primary_10_3390_biomedicines12081822 crossref_primary_10_1089_adt_2024_121 crossref_primary_10_1016_j_ejpb_2024_114292
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Keywords	Thermosassemble Ionizable reverse pluronic Bcl2 siRNA Blood brain barrier crossing Long-term stability
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Snippet	Thermosassemble Ionizable Reverse Pluronic (TIRP) platform stands out for its distinctive combination of thermoassemble and ionizable features, effectively...
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SubjectTerms	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
Title	Optimizing long-term stability of siRNA using thermoassemble ionizable reverse pluronic-Bcl2 micelleplexes
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