Evidence map›Paper›PMID 24810114›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2014

Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis.

Hamed Laroui, Emilie Viennois, Bo Xiao, Brandon S B Canup, Duke Geem, Timothy L Denning, Didier Merlin

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 153 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Hamed LarouiDepartment Chemistry and Biology, Center Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA. Electronic address: hlaroui@gsu.edu.
Emilie ViennoisInstitute for Biomedical Sciences, USA; Department Chemistry and Biology, Center Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA; Veterans Affair Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA.
Bo XiaoInstitute for Biomedical Sciences, USA; Department Chemistry and Biology, Center Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA.
Brandon S B CanupDepartment Chemistry and Biology, Center Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA.
Duke GeemInstitute for Biomedical Sciences, USA; Center for Inflammation, Immunity, & Infection, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA.
Timothy L DenningInstitute for Biomedical Sciences, USA; Center for Inflammation, Immunity, & Infection, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA.
Didier MerlinInstitute for Biomedical Sciences, USA; Department Chemistry and Biology, Center Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA; Veterans Affair Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Center for Inflammation, Immunity, & Infection, Georgia State University, 100 Piedmont Avenue, Atlanta, GA 30303, USA.
Georgia State University · USFoundation for Biomedical Research · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008169 · NIGMS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 1987 to 2021
$20.3M
ROLE OF CD98 IN INTESTINAL PERMEABILITYR01DK071594 · NIDDK · GEORGIA STATE UNIVERSITY · PI MERLIN, DIDIER · 2006 to 2017
$3.3M
Role of CD98 Glycoprotein in Intestinal InflammationK01DK097192 · NIDDK · GEORGIA STATE UNIVERSITY · PI LAROUI, HAMED · 2012 to 2016
$500k
NIDDK NIH HHS K01 DK097192NIDDK NIH HHS K01-DK-097192NIDDK NIH HHS R01 DK071594NIDDK NIH HHS R01-DK-071594NIGMS NIH HHS T32 GM008169
6 · The paper itself

Abstract

Patients suffering from inflammatory bowel disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab' portion of the F4/80 Ab (Fab'-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab'-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab'-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab'-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab'-bearing NPs loaded with TNFα siRNA than without the Fab'-bearing. Grafting the Fab'-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab'-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages.

Indexed as

AnimalsAntibodiesAntigens, DifferentiationCell LineColitisColonDextran SulfateImmunoglobulin Fab FragmentsMacrophagesMiceNanoparticlesPolyethylene GlycolsRNA, Small InterferingTumor Necrosis Factor-alphaAntibodiesAntigens, DifferentiationDextran SulfateImmunoglobulin Fab Fragmentsmonocyte-macrophage differentiation antigenmonomethoxypolyethyleneglycol-polylactide block copolymerPolyethylene GlycolsRNA, Small InterferingTumor Necrosis Factor-alphaDSS induced colitisLigand-mediated targetingTargeted siRNA releaseTNF secretion

Identifiers

PMID24810114
PMCPMC4100604
OpenAlexW1992529637

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.