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Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6
Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal.
Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal;Inst Invest & Formacao Avancada Ciencias & Tecnol, CESPU, Gandra, Portugal;Inst Univ Ciencias Saude, Gandra, Portugal.
Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal.
Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal.
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2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 81, p. 208-218Article in journal (Refereed) Published
Abstract [en]

Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 mu g/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6(+) carcinomas. Statement of Significance The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.

Place, publisher, year, edition, pages
2018. Vol. 81, p. 208-218
Keywords [en]
Human CD44v6, Targeted drug delivery, Antibody-conjugated nanoparticles, PLGA nanoparticles, Theranostics
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-372718DOI: 10.1016/j.actbio.2018.09.043ISI: 000451937500016PubMedID: 30267881OAI: oai:DiVA.org:uu-372718DiVA, id: diva2:1276656
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved

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Nestor, Marika

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