Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery
The growing significance of messenger RNA (mRNA) therapeutics in diverse medical applications, such as cancer, infectious diseases, and genetic disorders, highlighted the need for efficient and safe delivery systems. Lipid nanoparticles (LNPs) have shown great promise for mRNA delivery, but challeng...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/9/2291 |
| _version_ | 1797577972840923136 |
|---|---|
| author | Xuan Du Erica Yada Yuki Terai Takuya Takahashi Hideyuki Nakanishi Hiroki Tanaka Hidetaka Akita Keiji Itaka |
| author_facet | Xuan Du Erica Yada Yuki Terai Takuya Takahashi Hideyuki Nakanishi Hiroki Tanaka Hidetaka Akita Keiji Itaka |
| author_sort | Xuan Du |
| collection | DOAJ |
| description | The growing significance of messenger RNA (mRNA) therapeutics in diverse medical applications, such as cancer, infectious diseases, and genetic disorders, highlighted the need for efficient and safe delivery systems. Lipid nanoparticles (LNPs) have shown great promise for mRNA delivery, but challenges such as toxicity and immunogenicity still remain to be addressed. In this study, we aimed to compare the performance of polyplex nanomicelles, our original cationic polymer-based carrier, and LNPs in various aspects, including delivery efficiency, organ toxicity, muscle damage, immune reaction, and pain. Our results showed that nanomicelles (PEG-PAsp(DET)) and LNPs (SM-102) exhibited distinct characteristics, with the former demonstrating relatively sustained protein production and reduced inflammation, making them suitable for therapeutic purposes. On the other hand, LNPs displayed desirable properties for vaccines, such as rapid mRNA expression and potent immune response. Taken together, these results suggest the different potentials of nanomicelles and LNPs, supporting further optimization of mRNA delivery systems tailored for specific purposes. |
| first_indexed | 2024-03-10T22:15:42Z |
| format | Article |
| id | doaj.art-bbea13e3452e44a6b84880f314df846f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T22:15:42Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bbea13e3452e44a6b84880f314df846f2023-11-19T12:27:42ZengMDPI AGPharmaceutics1999-49232023-09-01159229110.3390/pharmaceutics15092291Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA DeliveryXuan Du0Erica Yada1Yuki Terai2Takuya Takahashi3Hideyuki Nakanishi4Hiroki Tanaka5Hidetaka Akita6Keiji Itaka7Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo 101-0062, JapanThe growing significance of messenger RNA (mRNA) therapeutics in diverse medical applications, such as cancer, infectious diseases, and genetic disorders, highlighted the need for efficient and safe delivery systems. Lipid nanoparticles (LNPs) have shown great promise for mRNA delivery, but challenges such as toxicity and immunogenicity still remain to be addressed. In this study, we aimed to compare the performance of polyplex nanomicelles, our original cationic polymer-based carrier, and LNPs in various aspects, including delivery efficiency, organ toxicity, muscle damage, immune reaction, and pain. Our results showed that nanomicelles (PEG-PAsp(DET)) and LNPs (SM-102) exhibited distinct characteristics, with the former demonstrating relatively sustained protein production and reduced inflammation, making them suitable for therapeutic purposes. On the other hand, LNPs displayed desirable properties for vaccines, such as rapid mRNA expression and potent immune response. Taken together, these results suggest the different potentials of nanomicelles and LNPs, supporting further optimization of mRNA delivery systems tailored for specific purposes.https://www.mdpi.com/1999-4923/15/9/2291messenger RNA (mRNA)lipid nanoparticle (LNP)polyplex nanomicelle |
| spellingShingle | Xuan Du Erica Yada Yuki Terai Takuya Takahashi Hideyuki Nakanishi Hiroki Tanaka Hidetaka Akita Keiji Itaka Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery Pharmaceutics messenger RNA (mRNA) lipid nanoparticle (LNP) polyplex nanomicelle |
| title | Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery |
| title_full | Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery |
| title_fullStr | Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery |
| title_full_unstemmed | Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery |
| title_short | Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery |
| title_sort | comprehensive evaluation of lipid nanoparticles and polyplex nanomicelles for muscle targeted mrna delivery |
| topic | messenger RNA (mRNA) lipid nanoparticle (LNP) polyplex nanomicelle |
| url | https://www.mdpi.com/1999-4923/15/9/2291 |
| work_keys_str_mv | AT xuandu comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT ericayada comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT yukiterai comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT takuyatakahashi comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT hideyukinakanishi comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT hirokitanaka comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT hidetakaakita comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery AT keijiitaka comprehensiveevaluationoflipidnanoparticlesandpolyplexnanomicellesformuscletargetedmrnadelivery |