Intracellular Delivery of Active Proteins by Polyphosphazene Polymers

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dc.contributor.authorQamar, Bareera
dc.contributor.authorSolomon, Melani
dc.contributor.authorMarin, Alexander
dc.contributor.authorFuerst, Thomas R.
dc.contributor.authorAndrianov, Alexander K.
dc.contributor.authorMuro, Silvia
dc.date.accessioned2023-11-06T19:19:13Z
dc.date.available2023-11-06T19:19:13Z
dc.date.issued2021-02-10
dc.description.abstractAchieving 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.
dc.description.urihttps://doi.org/10.3390/pharmaceutics13020249
dc.identifierhttps://doi.org/10.13016/dspace/qnhb-gntd
dc.identifier.citationQamar, B.; Solomon, M.; Marin, A.; Fuerst, T.R.; Andrianov, A.K.; Muro, S. Intracellular Delivery of Active Proteins by Polyphosphazene Polymers. Pharmaceutics 2021, 13, 249.
dc.identifier.urihttp://hdl.handle.net/1903/31283
dc.language.isoen_US
dc.publisherMDPI
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtChemistry & Biochemistryen_us
dc.relation.isAvailableAtCollege of Computer, Mathematical & Natural Sciencesen_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectpolyphosphazene polymers
dc.subjectintracellular protein delivery
dc.subjectendosomal escape
dc.subjectcytosolic delivery
dc.subjectintrecellular delivery of antibody
dc.subjectdelivery of apoptotic peptides
dc.subjectcytotoxicity
dc.titleIntracellular Delivery of Active Proteins by Polyphosphazene Polymers
dc.typeArticle
local.equitableAccessSubmissionNo

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