John Garner

PEG-PLGAs and PLGA-Fluorescent polymers from PolySciTech used in development of concurrent Chemo-Immuno-Radiotherapy methodology for cancer treatment

Blog Post created by John Garner on Feb 4, 2019

2019 University of North Carolina cancer polyscitech.gif

Lymphoma is a form of cancer which affects immune cells within the human body causing them to grow in pathological ways. It is a very common, and often difficult to treat, form of cancer. Treatments for cancer can take many forms however there has been evidence that combining treatments of multiple types (e.g. chemotherapy and radiotherapy) can have an impact on the cancer which is greater than simply the additive effects of each type of therapy. Recently, researchers at University of North Carolina at Chapel Hill, SHAL Technologies, Inc., and Levine Cancer Institute utilized mPEG-PLGA (AK101), PLA-PEG-NHS (AI068), and PLGA-rhodamine (AV027) from PolySciTech (www.polyscitech.com) to generate doxorubicin-loaded nanoparticles decorated with Selective High-Affinity Ligands (SHAL) for targeting to lymphoma. By combining this nanoparticle therapy with other methods, such as radiotherapy, they were able to eradicate lymphoma at a success rate of 80% in a mouse model. This research holds promise to provide for improved cancer therapy against this common and difficult to treat form of cancer. Read more: Au, Kin Man, Rod Balhorn, Monique C. Balhorn, Steven I. Park, and Andrew Z. Wang. "High-Performance Concurrent Chemo-Immuno-Radiotherapy for the Treatment of Hematologic Cancer through Selective High-Affinity Ligand Antibody Mimic-Functionalized Doxorubicin-Encapsulated Nanoparticles." ACS Central Science (2019). https://pubs.acs.org/doi/abs/10.1021/acscentsci.8b00746

“Abstract: Non-Hodgkin lymphoma is one of the most common types of cancer. Relapsed and refractory diseases are still common and remain significant challenges as the majority of these patients eventually succumb to the disease. Herein, we report a translatable concurrent chemo-immuno-radiotherapy (CIRT) strategy that utilizes fully synthetic antibody mimic Selective High-Affinity Ligand (SHAL)-functionalized doxorubicin-encapsulated nanoparticles (Dox NPs) for the treatment of human leukocyte antigen-D related (HLA-DR) antigen-overexpressed tumors. We demonstrated that our tailor-made antibody mimic-functionalized NPs bound selectively to different HLA-DR-overexpressed human lymphoma cells, cross-linked the cell surface HLA-DR, and triggered the internalization of NPs. In addition to the direct cytotoxic effect by Dox, the internalized NPs then released the encapsulated Dox and upregulated the HLA-DR expression of the surviving cells, which further augmented immunogenic cell death (ICD). The released Dox not only promotes ICD but also sensitizes the cancer cells to irradiation by inducing cell cycle arrest and preventing the repair of DNA damage. In vivo biodistribution and toxicity studies confirm that the targeted NPs enhanced tumor uptake and reduced systemic toxicities of Dox. Our comprehensive in vivo anticancer efficacy studies using lymphoma xenograft tumor models show that the antibody-mimic functional NPs effectively inhibit tumor growth and sensitize the cancer cells for concurrent CIRT treatment without incurring significant side effects. With an appropriate treatment schedule, the SHAL-functionalized Dox NPs enhanced the cell killing efficiency of radiotherapy by more than 100% and eradicated more than 80% of the lymphoma tumors.”

Outcomes