PLGA-PEG-Mal from PolySciTech used in development of Saporin-loaded Nanoparticle for HER2+ Breast Cancer Therapy

Human epidermal growth factor receptor 2 (HER2) is a specific marker which is over-expressed on certain types of breast cancer and provides an opportunity for targeting nanoparticles towards the tumor cells. Similar to ricin toxin, saporin inactivates a cells ability to synthesize proteins which ultimately leads to the cells death. Unlike ricin, however, saporin has no inherent mechanism to actually enter a cell and as such presents no toxicity unless a specific mechanism is provided for it to enter the cell. Recently, researchers at Utrecht University (Netherlands) used PLGA-PEG-Mal (AI020) from PolySciTech (www.polyscitech.com) in research to create targeted nanoparticles which bind to HER2 marker on breast cancer and used photochemical delivery to introduce saporin into these cells leading to tumor death. This research holds promise to enable the treatment of highly metastatic and treatment-resistant forms of breast cancer. Read more: Martinez Jothar, Lucia, Nataliia Beztsinna, Cornelus F. van Nostrum, Wim E. Hennink, and Sabrina Oliveira. "Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination With Photochemical Internalization." Molecular Pharmaceutics. https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01318

“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.”

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