Monday, July 9, 2018

Fluorescently-labeled and reactive-endcap polymers from PolySciTech used in development of photo-activated immunotherapy for treatment of cancer


Due to the fact that tumors are comprised of human patient cells, it is very difficult to create therapies which are selective in their damage against tumors. Most conventional treatments (chemotherapy, radiation, and surgical techniques) damage healthy tissue to some degree or another which limits the applicability of the treatment and causes a variety of side-effects for the patient. Recently, researchers at University of Maryland and Harvard University used Polyvivo reactive-endcap PLGA-PEG-COOH (Cat# AI034) and PLGA-PEG-azide (Cat# AI085) as well as fluorescent-endcap mPEG-PLGA-FKR560 (Cat# AV021) from PolySciTech (www.polyscitech.com) to create a photo-immunoconjugated nanoparticle. The unique feature of this particle is that it did not affect tissue until ‘triggered’ to do so by a light source allowing it to be targeted for affecting the cancer with great specificity. The researchers applied a unique technique of using a fluorescent end-cap PEG-PLGA, typically only used for tracking purposes, to serve as the trigger for these nanoparticles. This research holds promise for improved cancer therapies in the future. Read more: Huang, Huang‐Chiao, Michael Pigula, Yanyan Fang, and Tayyaba Hasan. "Immobilization of Photo‐Immunoconjugates on Nanoparticles Leads to Enhanced Light‐Activated Biological Effects." Small (2018): 1800236. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201800236

“Abstract: The past three decades have witnessed notable advances in establishing photosensitizer–antibody photo‐immunoconjugates for photo‐immunotherapy and imaging of tumors. Photo‐immunotherapy minimizes damage to surrounding healthy tissue when using a cancer‐selective photo‐immunoconjugate, but requires a threshold intracellular photosensitizer concentration to be effective. Delivery of immunoconjugates to the target cells is often hindered by I) the low photosensitizer‐to‐antibody ratio of photo‐immunoconjugates and II) the limited amount of target molecule presented on the cell surface. Here, a nanoengineering approach is introduced to overcome these obstacles and improve the effectiveness of photo‐immunotherapy and imaging. Click chemistry coupling of benzoporphyrin derivative (BPD)–Cetuximab photo‐immunoconjugates onto FKR560 dye‐containing poly(lactic‐co‐glycolic acid) nanoparticles markedly enhances intracellular photo‐immunoconjugate accumulation and potentiates light‐activated photo‐immunotoxicity in ovarian cancer and glioblastoma. It is further demonstrated that co‐delivery and light activation of BPD and FKR560 allow longitudinal fluorescence tracking of photoimmunoconjugate and nanoparticle in cells. Using xenograft mouse models of epithelial ovarian cancer, intravenous injection of photo‐immunoconjugated nanoparticles doubles intratumoral accumulation of photo‐immunoconjugates, resulting in an enhanced photoimmunotherapy‐mediated tumor volume reduction, compared to “standard” immunoconjugates. This generalizable “carrier effect” phenomenon is attributed to the successful incorporation of photo‐immunoconjugates onto a nanoplatform, which modulates immunoconjugate delivery and improves treatment outcomes.”

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