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Functional Nanocarriers for Drug Delivery by Surface Engineering of Polymeric Nanoparticle Post-Polymerization-Induced Self-Assembly
KTH, Polymera material.ORCID iD: 0000-0002-5010-5391
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2021 (English)In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 4, no 1, p. 1045-1056Article in journal (Refereed) Published
Abstract [en]

Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e., corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse, and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. The surface engineering of the PAA-b-PBA NP post-PISA were explored using a two-step approach. The hydrophilic NP-shell corona was modified with allyl groups under mild conditions, using allylamine in water, which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bioconjugation. The allyl-NPs were subsequently conjugated with a thiol-functional fluorescent dye (BODIPY-SH) to the allyl groups using "thiol-ene"-click chemistry, to mimic the attachment of a thiol-functional target ligand. The successful attachment of BODIPY-SH to the allyl-NPs was corroborated by UV-vis spectroscopy, showing the characteristic absorbance of the BODIPY-fluorophore at 500 nm. Despite modification of NPs with allyl groups and attachment of BODIPY-SH, the NPs retained their colloidal stability and monodispersity as indicated by DLS. This demonstrates that post-PISA functionalization is a robust method for synthesizing functional NPs. Neither the NPs nor allyl-NPs showed significant cytotoxicity toward RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. The cellular uptake of the NPs using J774A cells in vitro was found to be time and concentration dependent. The anti-cancer drug doxorubicin was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small initial burst release during the first 2 h, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method for functionalizing polymeric NP post-PISA to produce carriers designed for targeted drug delivery.

Place, publisher, year, edition, pages
American Chemical Society , 2021. Vol. 4, no 1, p. 1045-1056
Keywords [en]
doxorubicin (DOX), drug delivery, engineered NPs, nanoparticles (NPs), post-PISA functionalization, RAFT-mediated emulsion polymerization, Cell culture, Controlled drug delivery, Diagnosis, Disease control, Diseases, Emulsification, Emulsion polymerization, Hydrophilicity, Nanoparticles, Organic polymers, Self assembly, Ultraviolet visible spectroscopy, Colloidal Stability, Concentration-dependent, Hydrophobic monomers, N-butyl acrylate (nBA), Polymeric nanoparticles, Reversible addition fragmentation chain transfer, Surface engineering, UV-vis spectroscopy, Targeted drug delivery
National Category
Polymer Chemistry
Identifiers
URN: urn:nbn:se:miun:diva-46886DOI: 10.1021/acsabm.0c01552ISI: 000643599900082Scopus ID: 2-s2.0-85099056390OAI: oai:DiVA.org:miun-46886DiVA, id: diva2:1728837
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QC 20210525

Available from: 2021-04-15 Created: 2023-01-19Bibliographically approved

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Nilsson, FritjofHedenqvist, Mikael S.

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