Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications
| العنوان: | Synthesis and Characterization of Click Nucleic Acid Conjugated Polymeric Microparticles for DNA Delivery Applications |
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| المؤلفون: | Emerson L. Grey, Stephanie J. Bryant, Nicholas J. Bongiardina, Christopher N. Bowman, Alex J. Anderson |
| المصدر: | Biomacromolecules |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Polymers and Plastics, Polymers, Dispersity, Bioengineering, 02 engineering and technology, Conjugated system, 010402 general chemistry, 01 natural sciences, Article, Polymerization, Biomaterials, chemistry.chemical_compound, Nucleic Acids, Complementary DNA, Materials Chemistry, Sulfhydryl Compounds, Particle Size, Microparticle, Dispersion polymerization, Chemistry, DNA, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Thymine, Nucleic acid, Biophysics, 0210 nano-technology |
| الوصف: | Microparticle-mediated nucleic acid delivery is a popular strategy to achieve therapeutic outcomes via antisense gene therapy. However, current methods used to fabricate polymeric microparticles suffer from suboptimal properties such as particle polydispersity and low encapsulation efficiency. Here, a new particulate delivery system based on step-growth thiol-Michael dispersion polymerization, is reported in which a low polydispersity microparticle is functionalized with a synthetic nucleic acid mimic, namely click nucleic acids (CNA). CNA oligomers, exhibiting an average length of approximately four nucleic acid repeat units per chain for both adenine and thymine bases, were successfully conjugated to excess thiols present in the microparticles. Effective DNA loading was obtained by simple mixing; and, up to 6 ± 2 pmol of complementary DNA/mg of particle was achieved, depending on the length of DNA used. In addition, DNA loading was orders of magnitude less for noncomplementary sequences and sequences containing an alternating base mismatch. The DNA release properties were evaluated, and it was found that release could be triggered by sudden changes in temperature but was unaffected over a range of pH. Finally, phagocytosis of loaded microparticles was observed by confocal microscopy and corroborated by an increase in cellular metabolic activity up to 90%. Overall, this work suggests that CNA functionalized microparticles could be a promising platform for controlled DNA delivery. |
| تدمد: | 1526-4602 1525-7797 |
| DOI: | 10.1021/acs.biomac.0c01563 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4a72d5de0db8fa6e7fa91d8c7c35509 https://doi.org/10.1021/acs.biomac.0c01563 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a4a72d5de0db8fa6e7fa91d8c7c35509 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15264602 15257797 |
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| DOI: | 10.1021/acs.biomac.0c01563 |