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Functional Nanocarr...
Functional Nanocarriers for Drug Delivery by Surface Engineering of Polymeric Nanoparticle Post-Polymerization-Induced Self-Assembly
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Asem, H. (author)
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Zheng, W. (author)
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- Nilsson, Fritjof, Docent, 1978- (author)
- KTH,Polymera material,KTH, Polymera material
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Zhang, Y. (author)
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- Hedenqvist, Mikael S. (author)
- KTH,Polymera material,KTH, Polymera material
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Hassan, M. (author)
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Malmström, E. (author)
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(creator_code:org_t)
- 2020-12-22
- 2021
- English.
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In: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 4:1, s. 1045-1056
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Kemi -- Polymerkemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Polymer Chemistry (hsv//eng)
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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