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Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination With Photochemical Internalization
- Source :
- Molecular Pharmaceutics, Molecular Pharmaceutics, 16(4), 1633. American Chemical Society
- Publication Year :
- 2019
-
Abstract
- In cancer treatment, polymeric nanoparticles (NPs) can serve as a vehicle for the delivery of cytotoxic proteins that have intracellular targets but that lack well-defined mechanisms for cellular internalization, such as saporin. In this work we have prepared PEGylated poly(lactic acid-co-glycolic acid-co-hydroxymethyl glycolic acid) (PLGHMGA) NPs for the selective delivery of saporin in the cytosol of HER2 positive cancer cells. This selective uptake was achieved by decorating the surface of the NPs with the 11A4 nanobody that is specific for the HER2 receptor. Confocal microscopy observations showed rapid and extensive uptake of the targeted NPs (11A4-NPs) by HER2 positive cells (SkBr3), but not by HER2 negative cells (MDA-MB-231). This selective uptake was blocked upon pre-incubation of the cells with an excess of nanobody. Non-targeted NPs (Cys-NPs) were not taken up by either type of cells. Importantly, a dose-dependent cytotoxic effect was only observed on SkBr3 cells when these were treated with saporin-loaded 11A4-NPs in combination with photochemical internalization (PCI), a technique that uses a photosensitizer and local light exposure to facilitate endosomal escape of entrapped nanocarriers and biomolecules. The combined use of saporin-loaded 11A4-NPs and PCI strongly inhibited cell proliferation and decreased cell viability through induction of apoptosis. Also the cytotoxic effect could be reduced by an excess of nanobody, reinforcing the selectivity of this system. These results suggest that the combination of the targeting nanobody on the NPs with PCI are effective means to achieve selective uptake and cytotoxicity of saporin-loaded NPs.
- Subjects :
- Saporin
Polymers
Receptor, ErbB-2
Pharmaceutical Science
Apoptosis
02 engineering and technology
030226 pharmacology & pharmacy
Drug Delivery Systems
0302 clinical medicine
Drug Discovery
Tumor Cells, Cultured
Cytotoxic T cell
Internalization
Cytotoxicity
health care economics and organizations
media_common
Drug Carriers
Photosensitizing Agents
biology
Chemistry
PLGA
021001 nanoscience & nanotechnology
polymeric nanoparticles
SKBR3
Molecular Medicine
Female
0210 nano-technology
therapeutics
Polyesters
media_common.quotation_subject
education
Antineoplastic Agents
Breast Neoplasms
Article
03 medical and health sciences
mental disorders
Humans
Viability assay
targeting
Cell Proliferation
saporin
photochemical internalization
technology, industry, and agriculture
Single-Domain Antibodies
Saporins
nanobody
Photochemotherapy
Cancer cell
biology.protein
Biophysics
Nanoparticles
Nanocarriers
Subjects
Details
- Language :
- English
- ISSN :
- 15438384
- Database :
- OpenAIRE
- Journal :
- Molecular Pharmaceutics, Molecular Pharmaceutics, 16(4), 1633. American Chemical Society
- Accession number :
- edsair.doi.dedup.....afc07484cb5d51e3a8edb42e1bc0e94a