PCL-PEI from PolySciTech used in development of Immunotherapy system

 

Immunotherapy is a promising area of treatment for cancer as it allows the bodies natural defense system to attack the tumor directly. Recently, researchers at Yeungnam University, Hanyang University, Daegu Haany University (Korea), Phenikaa University, and PHENIKAA Research and Technology Institute (Vietnam) used PCL-PEI (AO043) from PolySciTech (www.polyscitech.com) to create dabrafenib and miR-200c loaded nanoparticles to modify the immune response against cancer. This research holds promise to improve therapy against cancer. Read more: Nguyen, Hanh Thuy, Cao Dai Phung, Tuan Hiep Tran, Tung Thanh Pham, Tiep Tien Nguyen, Jee-Heon Jeong, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong, and Jong Oh Kim. "Manipulating immune system using nanoparticles for an effective cancer treatment: Combination of targeted therapy and checkpoint blockage miRNA." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920305514

“Abstract: Accumulating clinical data shows that less than half of patients are beneficial from PD-1/PD-L1 blockage therapy owing to the limited infiltration of effector immune cells into the tumor and abundant of the immunosuppressive factors in the tumor microenvironment. In this study, PD-L1 inhibition therapy and BRAF-targeted therapy, which showed clinical benefit, were combined in a CXCR4-targeted nanoparticle co-delivering dabrafenib (Dab), a BRAF inhibitor, and miR-200c which can down-regulate PD-L1 expression. The cationic PCL-PEI core containing Dab- and miR-200c- were coated with poly-L-glutamic acid conjugated with LY2510924, a CXCR-4 antagonist peptide, (PGA-pep) to obtain miR@PCL-PEI/Dab@PGA-pep nanoformulation. The stimulus pH- and redox- reactive of PGA-pep was ascribed to exhibit an enhanced release of drug in the tumor microenvironment as well as improve the stability of miR-200c during the blood circulation. In addition, the presence of LY2510924 peptide would enhance the binding affinity of miR@PCL-PEI/Dab@PGA-pep NPs to cancer cells, leading to improved cellular uptake, cytotoxicity, and in vivo accumulation into tumor area. The in vivo results indicated that both, the immunogenic cell death (ICD) and the inhibition of PD-L1 expression, induced by treatment with CXCR-4 targeted nanoparticles, enables to improve the DC maturation in lymph node and CD8+ T cell activation in the spleen. More importantly, effector T cells were increasingly infiltrated into the tumor, whereas the immunosuppressive factors like PD-L1 expression and regulatory T cells were significantly reduced. They, all together, promote the immune responses against the tumor, indicating the therapeutic efficiency of the current strategy in cancer treatment.”