Evidence map›Paper›PMID 34481054›Full record

ArticleActa biomaterialia2021

A design approach for layer-by-layer surface-mediated siRNA delivery.

Jonathan J Chou, Adam G Berger, Sasan Jalili-Firoozinezhad, Paula T Hammond

Abstract read
In one paragraph

Article in Acta biomaterialia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Targeting and monitoring ovarian cancer invasion with an RNAi and peptide delivery system.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
  9. Article
  10. Review
  11. 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

4 authors.

Jonathan J ChouInstitute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address: jonchou@alum.mit.edu.
Adam G BergerInstitute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address: agberger@mit.edu.
Sasan Jalili-FiroozinezhadKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address: sjalili@mit.edu.
Paula T HammondInstitute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address: hammond@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Delivery of cytokines for cancer immunotherapy using nanolayer-controlled trafficking of liposomal nanoparticlesR01CA235375 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond, Darrell J Irvine · 2019 to 2026
$2.3M
Tunable Nanolayer-Polymer Composite Patches for Cell-Free CMF RepairR01DE024747 · NIDCR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HAMMOND, PAULA T · 2016 to 2020
$2.1M
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA235375NIDCR NIH HHS R01 DE024747
6 · The paper itself

Abstract

The ability to coat scaffolds and wound dressings with therapeutic short interfering RNA (siRNA) holds much potential for applications in wound healing, cancer treatment, and regenerative medicine. Layer-by-layer (LbL) technology is an effective method to formulate polyelectrolyte thin films for local delivery of siRNA; however, the formation and efficacy of LbL coatings as drug delivery systems are highly contingent on the assembly conditions. Here, we investigate the effects of LbL assembly parameters on film composition and consequent siRNA-mediated gene knockdown efficiency in vitro. Films comprising poly(β-amino ester) (PBAE) and siRNA were built on polyglactin 910 (Vicryl) sutures consisting of poly(10% L-lactide, 90% glycolide). A fractional factorial design was employed, varying the following LbL assembly conditions: pH, ionic strength, PBAE concentration, and siRNA concentration. Effects of these parameters on PBAE loading, siRNA loading, their respective weight ratios, and in vitro siRNA-mediated knockdown were elucidated. The parameter effects were leveraged to create a rationally designed set of solution conditions that was predicted to give effective siRNA-mediated knockdown, but not included in any of the original experimental conditions. This level of knockdown with our rationally designed loading conditions (47%) is comparable to previous formulations from our lab while being simpler in construction and requiring fewer film layers, which could save time and cost in manufacturing. This study highlights the importance of LbL solution conditions in the preparation of surface-mediated siRNA delivery systems and presents an adaptable methodology for extending these electrostatically-assembled coatings to the delivery of other therapeutic nucleic acids. STATEMENT OF SIGNIFICANCE: Short interfering RNA (siRNA) therapeutics are powerful tools to silence aberrant gene expression in the diseased state; however, the clinical utility of these therapies relies on effective controlled delivery approaches. Electrostatic self-assembly through the layer-by-layer (LbL) process enables direct siRNA release from surfaces, but this method is highly dependent upon the specific solution conditions used. Here, we use a fractional factorial design to illustrate how these assembly conditions impact composition of siRNA-eluting LbL thin films. We then elucidate how these properties mediate in vitro transfection efficacy. Ultimately, this work presents a significant step towards understanding how optimization of assembly conditions for surface-mediated LbL delivery can promote transfection efficacy while reducing the processing and material required.

Indexed as

Drug Delivery SystemsWound HealingPolyelectrolytesRNA, Small InterferingTransfectionPolyelectrolytesRNA, Small InterferingDeliveryDesign of experimentLayer-by-layerPBAEsiRNA

Identifiers

PMID34481054
PMCPMC9316412

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.