Academic Journal
Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy
| Title: | Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy |
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| Authors: | Jisan Hong, Dahye Sim, Byung-Heon Lee, Vijaya Sarangthem, Rang-Woon Park |
| Source: | Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-24 (2024) |
| Publisher Information: | BMC, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Biotechnology LCC:Medical technology |
| Subject Terms: | miRNA-34a, Tumor targeting, ELP nanoparticle, IL-4 receptor, Cell penetrating peptide, Apoptosis, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5 |
| More Details: | Abstract 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. Graphical Abstract |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1477-3155 |
| Relation: | https://doaj.org/toc/1477-3155 |
| DOI: | 10.1186/s12951-024-02559-5 |
| Access URL: | https://doaj.org/article/d8f88be1330842fbaaca5ff448507bb2 |
| Accession Number: | edsdoj.8f88be1330842fbaaca5ff448507bb2 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 14773155 |
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| DOI: | 10.1186/s12951-024-02559-5 |
| Published in: | Journal of Nanobiotechnology |
| Language: | English |