Abstract
Peptide nucleic acids (PNAs) are a class of artificial oligonucleotide mimics that have garnered much attention as precision biotherapeutics for their efficient hybridization properties and their exceptional biological and chemical stability. However, the poor cellular uptake of PNA is a limiting factor to its more extensive use in biomedicine; encapsulation in nanoparticle carriers has therefore emerged as a strategy for internalization and delivery of PNA in cells. In this study, we demonstrate that PNA can be readily loaded into porous silicon nanoparticles (pSiNPs) following a simple salt-based trapping procedure thus far employed only for negatively charged synthetic oligonucleotides. We show that the ease and versatility of PNA chemistry also allows for producing PNAs with different net charge, from positive to negative, and that the use of differently charged PNAs enables optimization of loading into pSiNPs. Differently charged PNA payloads determine different release kinetics and allow modulation of the temporal profile of the delivery process. In vitro silencing of a set of specific microRNAs using a pSiNP-PNA delivery platform demonstrates the potential for biomedical applications.
Original language | English |
---|---|
Pages (from-to) | 4123-4131 |
Number of pages | 9 |
Journal | ACS Biomaterials Science and Engineering |
Volume | 8 |
Issue number | 10 |
DOIs | |
State | Published - Oct 10 2022 |
Bibliographical note
Publisher Copyright:© 2022 American Chemical Society. All rights reserved.
Funding
This work has been partially funded by the European Commission through a MSCA-RISE Project Nano Oligomed (grant no. 778133) and from the NSF (grant No. CBET-1603177) and the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC) (grant No. DMR-2011924). This research benefited from equipment and core facilities provided by the COMP-HUB Initiative of the Department of Chemistry, Life Sciences and Environmental Sustainability of the University of Parma and funded by the \u201CDepartments of Excellence\u201D program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022) and the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (grant no. ECCS-1542148). R.C. and R.G. acknowledge partial support from Fondazione Fibrosi Cistica (FFC#7/2018). This project received funding from the European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement No 704120 \u201CMIRNANO\u201D (A.B). This work has been partially funded by the European Commission through a MSCA-RISE Project Nano Oligomed (grant no. 778133) and from the NSF (grant No. CBET-1603177) and the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC) (grant No. DMR-2011924). This research benefited from equipment and core facilities provided by the COMP-HUB Initiative of the Department of Chemistry, Life Sciences and Environmental Sustainability of the University of Parma and funded by the \u201CDepartments of Excellence\u201D program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022) and the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure which is supported by the National Science Foundation (grant no. ECCS-1542148). R.C. and R.G. acknowledge partial support from Fondazione Fibrosi Cistica (FFC#7/2018). This project received funding from the European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement No 704120 \u201CMIRNANO\u201D (A.B).
Funders | Funder number |
---|---|
Department of Chemistry and Division of Medicinal Chemistry and Pharmaceutics | |
Life Sciences and Environmental Sustainability of the University of Parma | |
MSCA-RISE | |
Marie Skłodowska-Curie fellowship | |
European Commission | |
Department of Chemistry, University of York | |
UC San Diego Materials Research Science and Engineering Center | |
Ministero dell’Istruzione, dell’Università e della Ricerca | 2018-2022 |
Fondazione Fibrosi Cistica | FFC#7/2018 |
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China | 2011924, 1542148, CBET-1603177 |
H2020 Marie Skłodowska-Curie Actions | 704120 |
Horizon 2020 Framework Programme | 778133 |
Materials Research Science and Engineering Center, University of California, San Diego | DMR-2011924 |
Keywords
- anti-microRNA therapeutics
- drug delivery
- nanomaterials
- oligonucleotide mimics
- release kinetics
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering