Single-Domain Antibody-Functionalized pH-Responsive Amphiphilic Block Copolymer Nanoparticles for Epidermal Growth Factor Receptor Targeted Cancer Therapy

Thomas J. Gibson, Peter Smyth, William J. McDaid, Daniel Lavery, Jennifer Thom, Graham Cotton, Christopher J. Scott, Efrosyni Themistou

Research output: Contribution to journalArticle

3 Citations (Scopus)
58 Downloads (Pure)

Abstract

Biocompatible antibody–nanoparticle conjugates have attracted interest as anticancer agents due to their potential to selectively target therapeutic agents at disease sites. However, new formulation and conjugation approaches are urgently needed to improve their uniformity for clinical applications. Here, a pH-responsive benzaldehyde-functionalized poly[oligo(ethylene glycol) methacrylate-st-para-formyl phenyl methacrylate]-b-poly[2-(diisopropyl)aminoethyl methacrylate] [P(OEGMA-st-pFPMA)-b-PDPA] block copolymer, prepared by reversible addition–fragmentation chain transfer polymerization, produced PEGylated nanoparticles (pH ∼ 7.4) by a single emulsion-solvent evaporation formulation approach. Efficient site-specific attachment of an aminooxy-functionalized anti-EGFR single-domain antibody (sdAb) on these benzaldehyde-decorated nanoparticles is achieved by oxime bond formation. These nanoconjugates can specifically bind EGFR (modified ELISA) and have enhanced uptake over nonfunctionalized controls in EGFR-positive HeLa cells. Encapsulation of rhodamine 6G dye and its dispersion upon cellular uptake, consistent with nanoparticle stability loss at pH < 5.7, prove their ability to facilitate triggered release in endosomal compartments and highlight their potential for use as next-generation antibody–drug nanoconjugates for therapeutic drug delivery.
Original languageEnglish
Pages (from-to)1010-1015
JournalACS Macro Letters
Volume7
Issue number8
Early online date03 Aug 2018
DOIs
Publication statusPublished - 21 Aug 2018

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Single-Domain Antibodies
Nanoconjugates
Epidermal Growth Factor Receptor
Antibodies
Block copolymers
Nanoparticles
Oximes
Emulsions
Drug delivery
Encapsulation
Antineoplastic Agents
Polyethylene glycols
Evaporation
Coloring Agents
Dyes
Polymerization
Epidermal Growth Factor
benzaldehyde

Cite this

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title = "Single-Domain Antibody-Functionalized pH-Responsive Amphiphilic Block Copolymer Nanoparticles for Epidermal Growth Factor Receptor Targeted Cancer Therapy",
abstract = "Biocompatible antibody–nanoparticle conjugates have attracted interest as anticancer agents due to their potential to selectively target therapeutic agents at disease sites. However, new formulation and conjugation approaches are urgently needed to improve their uniformity for clinical applications. Here, a pH-responsive benzaldehyde-functionalized poly[oligo(ethylene glycol) methacrylate-st-para-formyl phenyl methacrylate]-b-poly[2-(diisopropyl)aminoethyl methacrylate] [P(OEGMA-st-pFPMA)-b-PDPA] block copolymer, prepared by reversible addition–fragmentation chain transfer polymerization, produced PEGylated nanoparticles (pH ∼ 7.4) by a single emulsion-solvent evaporation formulation approach. Efficient site-specific attachment of an aminooxy-functionalized anti-EGFR single-domain antibody (sdAb) on these benzaldehyde-decorated nanoparticles is achieved by oxime bond formation. These nanoconjugates can specifically bind EGFR (modified ELISA) and have enhanced uptake over nonfunctionalized controls in EGFR-positive HeLa cells. Encapsulation of rhodamine 6G dye and its dispersion upon cellular uptake, consistent with nanoparticle stability loss at pH < 5.7, prove their ability to facilitate triggered release in endosomal compartments and highlight their potential for use as next-generation antibody–drug nanoconjugates for therapeutic drug delivery.",
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Single-Domain Antibody-Functionalized pH-Responsive Amphiphilic Block Copolymer Nanoparticles for Epidermal Growth Factor Receptor Targeted Cancer Therapy. / Gibson, Thomas J.; Smyth, Peter; McDaid, William J.; Lavery, Daniel; Thom, Jennifer; Cotton, Graham; Scott, Christopher J.; Themistou, Efrosyni.

In: ACS Macro Letters, Vol. 7, No. 8, 21.08.2018, p. 1010-1015.

Research output: Contribution to journalArticle

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AU - Smyth, Peter

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AU - Lavery, Daniel

AU - Thom, Jennifer

AU - Cotton, Graham

AU - Scott, Christopher J.

AU - Themistou, Efrosyni

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