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Cited by 80RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryDendrimers and Hyperbranched Polymers

The Effect of N/ P Ratio on the In Vitro and In Vivo Interaction Properties of PEG ylated Poly[2‐(dimethylamino)ethyl methacrylate]‐ B ased si RNA Complexes

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Gary, Dana J., Min, Jungbin, Kim, Youngwook, Park, Keunchil, Won, You‐Yeon·2013·Macromolecular Bioscience
DOI 10.1002/mabi.201300046PMC PMC4121118
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Abstract

PEG‐PnBA‐PDMAEMA triblock and PEG‐PDMAEMA diblock copolymers are used as model systems for studying the role of N/P ratio on the in vivo behavior of PEGylated siRNA carriers in mice. The presence of a free/uncomplexed polymer population coexisting with siRNA complexes is established. A change in the N/P ratio exerts no significant influence on the in vivo biodistribution and ex vivo blood chemistry properties of the respective systems. Histological analysis of major organs indicates that the presence of uncomplexed polymer elicits toxicity to the organ that is associated with the clearance of the siRNA complexes from the circulation system. This effect can be eliminated by working at N/P ratios near the charge‐neutralization point of the complexes.

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  • The N:P ratio impacts both nucleic acid delivery and toxicity, with higher ratios leading to diminishing returns in cellular transfection due to increased cell death.

    “Previous studies have demonstrated that the N:P ratio impacts both nucleic acid delivery and toxicity, with higher ratios leading to diminishing returns in cellular transfection due to increased cell death (31).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [31]

    The Introduction (page not provided) says high N:P ratios can enhance intracellular delivery and in vitro gene expression, with higher toxicity as a trade-off. It does not say that cell death causes diminishing returns in cellular transfection; the toxicity it describes is systemic and linked to interactions with blood components. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Gary, D. J., Min, J., Kim, Y., Park, K., & Won, Y.
Affiliations
  • Purdue University West Lafayette (US)
  • Samsung Medical Center (KR)
  • Medical Nanoelement Development Center Samsung Medical Center Seoul 135‐710 Republic of Korea
Corresponding author
Park, Keunchil
ORCID
Venue
Macromolecular Bioscience
Publisher
Wiley
Published
2013-07-05
Volume
13
Issue
8
Pages
1059-1071
ISSN
  • 1616-5187 (ISSN-L)
  • 1616-5195
DOI
10.1002/mabi.201300046
PMC
PMC4121118
OpenAlex
W1895163001
Cited by
80
References
0
Citations by year
2026: 5 · 2025: 13 · 2024: 5 · 2023: 10 · 2022: 12 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2
FWCI
1.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Macromolecular Bioscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • US National Science Foundation (CBET-0828574 and DMR-0906567)
  • IUSM/CTR, NIH/NCRR (RR025761)
  • Korean Health 21 R&D Project Grant from the Ministry of Health & Welfare of the Korean Government (A040041)
  • Samsung Biomedical Research Institute (C-H1-103)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
N:P ratio, siRNA delivery, PDMAEMA, tissue distribution, serum biochemistry, organ toxicity, in vivo clearance
MeSH terms
Animals, Blood Chemical Analysis, Male, Methacrylates, Mice, Inbred BALB C, Mice, Inbred C57BL, Nitrogen, Nylons, Phosphates, Polyethylene Glycols, Polymers, Serum Albumin, Bovine, RNA Interference, RNA, Small Interfering, Mice

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