Evidence map›Paper›PMID 33578893›Full record

ArticlePharmaceutics2021

Intracellular Delivery of Active Proteins by Polyphosphazene Polymers.

Bareera Qamar, Melani Solomon, Alexander Marin, Thomas R Fuerst, Alexander K Andrianov, Silvia Muro

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

6 authors at 2 institutions in 2 countries.

Bareera QamarCollege of Mathematical and Natural Sciences, University of Maryland, College Park, MD 20742, USA.
Melani SolomonInstitute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
Alexander MarinInstitute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
Thomas R FuerstInstitute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
Alexander K AndrianovInstitute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, USA.ORCID 0000-0001-6186-6156
Silvia MuroInstitute for Bioscience and Biotechnology Research, University of Maryland, College Park, MD 20742, USA.
University of Maryland, College Park · USInstitute for Bioengineering of Catalonia · ES

Funding

Targeted replacement of defective lysosomal enzymes in the lung and brainR01HL098416 · NHLBI · UNIV OF MARYLAND, COLLEGE PARK · PI MURO, SILVIA · 2010 to 2020
$3.3M
Ministerio de Ciencia, Innovación y Universidades SAF2017-91909-EXPNHLBI NIH HHS R01 HL098416NIH HHS R01 HL98416University of Maryland MPower Program IBBR Seed Grant
6 · The paper itself

Abstract

Achieving intracellular delivery of protein therapeutics within cells remains a significant challenge. Although custom formulations are available for some protein therapeutics, the development of non-toxic delivery systems that can incorporate a variety of active protein cargo and maintain their stability, is a topic of great relevance. This study utilized ionic polyphosphazenes (PZ) that can assemble into supramolecular complexes through non-covalent interactions with different types of protein cargo. We tested a PEGylated graft copolymer (PZ-PEG) and a pyrrolidone containing linear derivative (PZ-PYR) for their ability to intracellularly deliver FITC-avidin, a model protein. In endothelial cells, PZ-PYR/protein exhibited both faster internalization and higher uptake levels than PZ-PEG/protein, while in cancer cells both polymers achieved similar uptake levels over time, although the internalization rate was slower for PZ-PYR/protein. Uptake was mediated by endocytosis through multiple mechanisms, PZ-PEG/avidin colocalized more profusely with endo-lysosomes, and PZ-PYR/avidin achieved greater cytosolic delivery. Consequently, a PZ-PYR-delivered anti-F-actin antibody was able to bind to cytosolic actin filaments without needing cell permeabilization. Similarly, a cell-impermeable Bax-BH3 peptide known to induce apoptosis, decreased cell viability when complexed with PZ-PYR, demonstrating endo-lysosomal escape. These biodegradable PZs were non-toxic to cells and represent a promising platform for drug delivery of protein therapeutics.

Indexed as

cytosolic deliverycytotoxicitydelivery of apoptotic peptidesendosomal escapeintracellular delivery of antibodyintracellular protein deliverypolyphosphazene polymers

Identifiers

PMID33578893
PMCPMC7916676
OpenAlexW3127792700

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.