دورية أكاديمية
أعرض في EDS

Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy.

التفاصيل البيبلوغرافية
العنوان: Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy.
المؤلفون: Hong J; Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, Kyungpook National University, School of Medicine, Daegu, 41944, Republic of Korea., Sim D; Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, Kyungpook National University, School of Medicine, Daegu, 41944, Republic of Korea., Lee BH; Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, Kyungpook National University, School of Medicine, Daegu, 41944, Republic of Korea., Sarangthem V; Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, Kyungpook National University, School of Medicine, Daegu, 41944, Republic of Korea. devi1703@gmail.com., Park RW; Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, Kyungpook National University, School of Medicine, Daegu, 41944, Republic of Korea. nwpark@knu.ac.kr.
المصدر: Journal of nanobiotechnology [J Nanobiotechnology] 2024 May 27; Vol. 22 (1), pp. 293. Date of Electronic Publication: 2024 May 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, 2003-
مواضيع طبية MeSH: MicroRNAs*/genetics , Elastin*/chemistry , Peptides*/chemistry , Nanoparticles*/chemistry, Animals ; Mice ; Humans ; Cell Line, Tumor ; Neoplasms/therapy ; Neoplasms/drug therapy ; Drug Carriers/chemistry ; Female ; Elastin-Like Polypeptides
مستخلص: Background: The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation.
Results: Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice.
Conclusions: Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 2021R1A5A2021614 National Research Foundation of Korea (NRF); 2021R1A5A2021614 National Research Foundation of Korea (NRF); 2021R1A5A2021614 National Research Foundation of Korea (NRF); 2021R1A5A2021614 National Research Foundation of Korea (NRF); 4199990714163 Brain Korea 21(BK21), Republic of Korea; 4199990714163 Brain Korea 21(BK21), Republic of Korea; 4199990714163 Brain Korea 21(BK21), Republic of Korea
فهرسة مساهمة: Keywords: 3D spheroid; Apoptosis; Cell penetrating peptide; ELP nanoparticle; IL-4 receptor; Tumor inhibition; Tumor targeting; miRNA-34a
المشرفين على المادة: 0 (MicroRNAs)
9007-58-3 (Elastin)
0 (Peptides)
0 (Drug Carriers)
0 (Elastin-Like Polypeptides)
تواريخ الأحداث: Date Created: 20240527 Date Completed: 20240528 Latest Revision: 20240530
رمز التحديث: 20240530
مُعرف محوري في PubMed: PMC11131307
DOI: 10.1186/s12951-024-02559-5
PMID: 38802812
قاعدة البيانات: MEDLINE
الوصف
تدمد:1477-3155
DOI:10.1186/s12951-024-02559-5