Evidence map›Paper›PMID 24780268›Full record

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

Protein polymer nanoparticles engineered as chaperones protect against apoptosis in human retinal pigment epithelial cells.

Wan Wang, Parameswaran G Sreekumar, Vinod Valluripalli, Pu Shi, Jiawei Wang, Yi-An Lin, Honggang Cui, Ram Kannan, David R Hinton, J Andrew MacKay

Abstract 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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022
    Review
  8. Article
  9. Small Heat Shock Proteins in Retinal Diseases.Frontiers in molecular biosciences · 2022
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
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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

10 authors at 3 institutions in 1 country.

Wan Wang *Department of Pharmacology and Pharmaceutical Sciences, University of Southern California Los Angeles, CA; 90033-9121.
Parameswaran G Sreekumar *Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA 90033.
Vinod ValluripalliDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Los Angeles, CA; 90033-9121.
Pu ShiDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Los Angeles, CA; 90033-9121.
Jiawei WangDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Los Angeles, CA; 90033-9121.
Yi-An LinDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, 21218, USA.
Honggang CuiDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, 21218, USA.
Ram KannanArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA 90033.
David R HintonDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033.
J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California Los Angeles, CA; 90033-9121.
University of Southern California · USDoheny Eye Institute · USJohns Hopkins University · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015
$36.0M
VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
EXPERIMENTAL APPROACH TO MACULOPATHYR01EY001545 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HINTON, DAVID R. · 1985 to 2016
$6.0M
A rapid, reversible switch for controlling intracellular traffickingR21EB012281 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACKAY, JOHN ANDREW · 2010 to 2011
$438k
NCATS NIH HHS UL1 TR000130NCATS NIH HHS UL1TR000130NCI NIH HHS P30 CA014089NEI NIH HHS P30 EY003040NEI NIH HHS P30 RO1EY03040NEI NIH HHS R01 EY001545NEI NIH HHS R01EY01545NIBIB NIH HHS R21 EB012281
6 · The paper itself

Abstract

αB-Crystallin is a protein chaperone with anti-apoptotic and anti-inflammatory activity that is apically secreted in exosomes by polarized human retinal pigment epithelium. A 20 amino acid mini-peptide derived from residues 73-92 of αB-crystallin protects human retinal pigment epithelial (RPE) cells from oxidative stress, a process involved in the progression of age-related macular degeneration (AMD). Unfortunately, due to its small size, its development as a therapeutic requires a robust controlled release system. To achieve this goal, the αB-crystallin peptide was re-engineered into a protein polymer nanoparticle/macromolecule with the purpose of increasing the hydrodynamic radius/molecular weight and enhancing potency via multivalency or an extended retention time. The peptide was recombinantly fused with two high molecular weight (~40kDa) protein polymers inspired by human tropoelastin. These elastin-like polypeptides (ELPs) include the following: (i) a soluble peptide called S96 and (ii) a diblock copolymer called SI that assembles multivalent nanoparticles at physiological temperature. Fusion proteins, cryS96 and crySI, were found to reduce aggregation of alcohol dehydrogenase and insulin, which demonstrates that ELP fusion did not diminish chaperone activity. Next their interaction with RPE cells was evaluated under oxidative stress. Unexpectedly, H2O2-induced stress dramatically enhanced cellular uptake and nuclear localization of both cryS96 and crySI ELPs. Accompanying uptake, both fusion proteins protected RPE cells from apoptosis, as indicated by reduced caspase 3 activation and TUNEL staining. This study demonstrates the in vitro feasibility of modulating the hydrodynamic radius for small peptide chaperones by seamless fusion with protein polymers; furthermore, they may have therapeutic applications in diseases associated with oxidative stress, such as AMD.

Indexed as

Drug CarriersMolecular ChaperonesNanoparticlesProtein EngineeringActive Transport, Cell Nucleusalpha-Crystallin B ChainApoptosisCaspase 3Cells, CulturedChemistry, PharmaceuticalCytoprotectionDelayed-Action PreparationsEnzyme ActivationEpithelial CellsFeasibility StudiesHumansalpha-Crystallin B ChainCASP3 protein, humanCaspase 3Delayed-Action PreparationsDrug CarriersMolecular ChaperonesPeptide FragmentsRecombinant Fusion ProteinsTropoelastinAnti-apoptosisAssemblyCell uptakeChaperoneElastin-like polypeptide (ELPs)

Identifiers

PMID24780268
PMCPMC4222838
OpenAlexW2064938364

What OpenQuestion holds

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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.