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Fab-conjugated PLGA...
Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6
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- Kennedy, Patrick J. (author)
- 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
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- Sousa, Flavia (author)
- 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
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- Ferreira, Daniel (author)
- Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal
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- Pereira, Carla (author)
- Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal
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- Nestor, Marika, 1976- (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Oliveira, Carla (author)
- Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal;Univ Porto, FMUP Fac Med, Porto, Portugal
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- Granja, Pedro L. (author)
- Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal;Univ Porto, FMUP Fac Med, Dept Engn Met & Mat, Porto, Portugal
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- Sarmento, Bruno (author)
- Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Inst Invest & Formacao Avancada Ciencias & Tecnol, CESPU, Gandra, Portugal;Inst Univ Ciencias Saude, Gandra, Portugal;Queens Univ Belfast, Sch Pharm, Ctr Med Biol, Belfast, Antrim, North Ireland
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 81, s. 208-218
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Human CD44v6
- Targeted drug delivery
- Antibody-conjugated nanoparticles
- PLGA nanoparticles
- Theranostics
Publication and Content Type
- ref (subject category)
- art (subject category)
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