Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization

Molecular Pharmaceutics
Lucía Martínez-JotharSabrina Oliveira

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 preincubation of the cells with an excess of nanobody. Nontargeted 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 comb...Continue Reading

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Citations

Feb 23, 2020·Journal of Clinical Medicine·Waseem JerjesKristian Berg
Aug 14, 2020·Journal of Drug Targeting·Mohd MugheesSaima Wajid
Aug 9, 2020·Macromolecular Rapid Communications·Nicholas L FletcherKristofer J Thurecht
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Nov 27, 2020·Frontiers in Cellular Neuroscience·Marit A de Beer, Ben N G Giepmans
Mar 1, 2020·Drug Discovery Today·Yunfeng LinLei Zhang
Apr 2, 2021·International Journal of Nanomedicine·Shuyang SunXiaoling Lu
Dec 29, 2020·Drug Discovery Today·Rakesh Kumar Dhritlahre, Ankit Saneja
Jun 16, 2021·ACS Applied Materials & Interfaces·Laura Sánchez-GarcíaArio de Marco
Sep 5, 2020·Recent Patents on Anti-cancer Drug Discovery·Long WangZuoyi Jiao

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Methods Mentioned

BETA
electron microscopy
Protein Assay
differential scanning calorimetry
dynamic light scattering
Assay
confocal microscopy

Software Mentioned

GraphPad Prism
ImageJ
ExPASy ProtParam

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