Wednesday, August 15, 2018

PLGA-NHS from PolySciTech used in development of hybrid nanoparticles for photo-immunotherapy as cancer treatment


The visible spectrum of light encompasses only a small sliver of available electromagnetic range. Light with wavelengths just slightly past the human visible range are referred to as near-infra-red light and such light is routinely used in house-hold items such as television remote controls and garage-door sensors. This light has the ability to pierce through human tissue and illuminate regions inside which gives it promise for use as a photo-activation method for cancer treatment. In photo-therapy, a medicine is applied which is not active until it encounters light. Afterwards, the region of the tumor is illuminated so that the therapy is activated only in that location. Recently, researchers from Yeungnam University, Daegu Haany University, and Hanyang University (Korea) used PLGA-NHS (PolyVivo AI097) from PolySciTech (www.polyscitech.com) to develop imatinib-loaded nanoparticles and conjugate the activated n-hydroxysuccinimide ester endcap of the PLGA to glucocorticoid-induced TNF receptor. These nanoparticles were tested and found to be activated by exposure to tissue-penetrating near-infrared light at 780 nm resulting in tumor necrosis. This research holds promise for treating cancers with minimal side-effects. Read more: Ou W, Jiang L, Thapa RK, Soe ZC, Poudel K, Chang JH, Ku SK, Choi HG, Yong CS, Kim JO. Combination of NIR therapy and regulatory T cell modulation using layer-by-layer hybrid nanoparticles for effective cancer photo-immunotherapy. Theranostics 2018; 8(17):4574-4590. doi:10.7150/thno.26758. Available from http://www.thno.org/v08p4574.htm

“The efficacy of combined near-infrared (NIR) and immune therapies for inhibiting tumor growth and recurrence has gained increasing research attention. Regulatory T cells in the tumor microenvironment constitute a major obstacle in achieving robust CD8+ T cell antitumor immunotherapy. In the present study, we designed a photoimmunotherapy-based strategy involving a combination of photothermal and photodynamic therapies, followed by Treg cell suppression, for eliciting an immune response with IR-780- and imatinib-loaded layer-by-layer hybrid nanoparticles. Methods: The layer-by-layer hybrid nanoparticles were prepared through electrostatic interactions. Their photothermal effect, photodynamic effect as well as their effect on inhibiting Treg cells' suppressive function were investigated in vitro and in vivo. Their antitumor effect was evaluated using B16/BL6 and MC-38 tumor-bearing mice. Results: The layer-by-layer hybrid nanoparticles, which were pH-sensitive, enabled the release of IR-780 dye for NIR-induced photothermal and photodynamic effects, and the release of imatinib-loaded glucocorticoid-induced TNF receptor family-related protein/poly(lactic-co-glycolic acid) (GITR-PLGA) nanoparticles to initiate antitumor immunotherapy. The photothermal and photodynamic effects caused by IR-780 under NIR exposure resulted in direct tumor apoptosis/necrosis and the production of tumor-associated antigen, promoted dendritic cell maturation, and enhanced the presentation of tumor-associated antigen to T cells, while the imatinib-loaded GITR-PLGA cores reduced the suppressive function of Treg cells, and consequently activated effective CD8+ T cells towards tumors. Conclusion: With the significant photothermal, photodynamic and immunotherapies, the system successfully eradicated tumor growth, diminished tumor recurrence, and improved survival in vivo. The proposed nanoparticles provide a novel and versatile approach to boost antitumor photoimmunotherapy. Keywords: imatinib, immunotherapy, IR-780, layer by layer, photodynamic therapy, photothermal therapy, Treg cell”

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