Evidence map›Paper›PMID 29232104›Full record

ArticleACS nano2018

The Effects of Biological Fluids on Colloidal Stability and siRNA Delivery of a pH-Responsive Micellar Nanoparticle Delivery System.

Dominic W Malcolm, Jomy J Varghese, Janet E Sorrells, Catherine E Ovitt, Danielle S W Benoit

Abstract read
In one paragraph

Article in ACS nano, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 72 citations in OpenAlex.

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  14. Review
  15. Review
  16. Article
  17. Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023
    Article
  18. Review
  19. Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA delivery.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Dominic W MalcolmDepartment of Biomedical Engineering, University of Rochester , Rochester, New York 14627, United States.
Jomy J VargheseDepartment of Biomedical Engineering, University of Rochester , Rochester, New York 14627, United States.
Janet E SorrellsDepartment of Biomedical Engineering, University of Rochester , Rochester, New York 14627, United States.
Catherine E OvittCenter for Oral Biology, University of Rochester , Rochester, New York 14627, United States.
Danielle S W BenoitDepartment of Biomedical Engineering, University of Rochester , Rochester, New York 14627, United States.ORCID 0000-0001-7137-8164
University of Rochester Medical Center · USUniversity of Rochester · US

Funding

Rochester Resource-Based Center for Bone, Muscle and Orthopaedic Research (ROCSTARR) (Overall Application)P30AR069655 · NIAMS · UNIVERSITY OF ROCHESTER · PI Edward M. Schwarz · 2016 to 2026
$7.8M
Tissue Engineering Strategies to Revitalize Bone AllograftsR01AR064200 · NIAMS · UNIVERSITY OF ROCHESTER · PI Danielle S. Benoit · 2013 to 2026
$4.0M
Engineering scarless repair of flexor tendon injuriesR01AR056696 · NIAMS · UNIVERSITY OF ROCHESTER · PI AWAD, HANI A, BENOIT, DANIELLE S. · 2009 to 2019
$3.6M
Evaluation of a Novel Anti-Caries Approach to Modulate Virulence of S. mutansR01DE018023 · NIDCR · UNIVERSITY OF ROCHESTER · PI KOO, HYUN · 2008 to 2019
$3.4M
Engineered salivary gland tissue chipsUG3DE027695 · NIDCR · UNIVERSITY OF ROCHESTER · PI BENOIT, DANIELLE S., DELOUISE, LISA A · 2017 to 2018
$1.5M
Salivary gland-specific radioprotectionR56DE025098 · NIDCR · UNIVERSITY OF ROCHESTER · PI BENOIT, DANIELLE S., OVITT, CATHERINE · 2016 to 2016
$531k
Engineered Nanoparticles to Radioprotect Salivary TissueF30CA206296 · NCI · UNIVERSITY OF ROCHESTER · PI VARGHESE, JOMY JO · 2016 to 2019
$192k
NCI NIH HHS F30 CA206296NIAMS NIH HHS P30 AR069655NIAMS NIH HHS R01 AR056696NIAMS NIH HHS R01 AR064200NIDCR NIH HHS R01 DE018023NIDCR NIH HHS R56 DE025098NIDCR NIH HHS UG3 DE027695
6 · The paper itself

Abstract

Nanoparticles (NPs) interact with complex protein milieus in biological fluids, and these interactions have profound effects on NP physicochemical properties and function. Surprisingly, most studies neglect the impact of these interactions, especially with respect to NP-mediated siRNA delivery. Here, the effects of serum on colloidal stability and siRNA delivery of a pH-responsive micellar NP delivery system were characterized. Results show cationic NP-siRNA complexes aggregate in ≥2% serum in buffer, but are stable in serum-free media. Furthermore, nonaggregated NP-siRNA delivered in serum-free media result in 4-fold greater siRNA uptake in vitro, compared to aggregated NP-siRNA. Interestingly, pH-responsive membrane lysis behavior, which is required for endosomal escape, and NP-siRNA dissociation, necessary for gene knockdown, are significantly reduced in serum. Consistent with these data, nonaggregated NP-siRNA in serum-free conditions result in highly efficient gene silencing, even at doses as low as 5 nM siRNA. NP-siRNA diameter was measured at albumin and IgG levels mimicking biological fluids. Neither albumin nor IgG alone induces NP-siRNA aggregation, implicating other serum proteins in NP colloidal instability. Finally, as a proof-of-principle that stability is maintained in established in vivo models, transmission electron microscopy reveals NP-siRNA are taken up by ductal epithelial cells in a nonaggregated state when injected retroductally into mouse salivary glands in vivo. Overall, this study shows serum-induced NP-siRNA aggregation significantly diminishes efficiency of siRNA delivery by reducing uptake, pH-responsive membrane lysis activity, and NP-siRNA dissociation. Moreover, these results highlight the importance of local NP-mediated drug delivery and are broadly applicable to other drug delivery systems.

Indexed as

MicellesAnimalsColloidsDelayed-Action PreparationsFemaleGene Transfer TechniquesHumansMiceMice, Inbred C57BLNanoparticlesRNA InterferenceRNA, Small InterferingSalivary GlandsSerumColloidsDelayed-Action PreparationsMicellesRNA, Small Interferingaggregationmesenchymal stem cellmicellenanoparticlesalivary glandserumsiRNA

Identifiers

PMID29232104
PMCPMC5987762
OpenAlexW2775265618

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.