Tuning the Loading and Release Properties of MicroRNA-Silencing Porous Silicon Nanoparticles by Using Chemically Diverse Peptide Nucleic Acid Payloads

Martina Neri, Jinyoung Kang, Jonathan M. Zuidema, Jessica Gasparello, Alessia Finotti, Roberto Gambari, Michael J. Sailor, Alessandro Bertucci, Roberto Corradini

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 languageEnglish
Pages (from-to)4123-4131
Number of pages9
JournalACS Biomaterials Science and Engineering
Volume8
Issue number10
DOIs
StatePublished - 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).

FundersFunder 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 Ricerca2018-2022
Fondazione Fibrosi CisticaFFC#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 China2011924, 1542148, CBET-1603177
H2020 Marie Skłodowska-Curie Actions704120
Horizon 2020 Framework Programme778133
Materials Research Science and Engineering Center, University of California, San DiegoDMR-2011924

    Keywords

    • anti-microRNA therapeutics
    • drug delivery
    • nanomaterials
    • oligonucleotide mimics
    • release kinetics

    ASJC Scopus subject areas

    • Biomaterials
    • Biomedical Engineering

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