Treatment with either radiation alone or with a nanoparticle containing a 'scrambled' siRNA molecule had no effect on either tumor growth or survival of the mice.
Administering an iRGD-guided nanoparticle carrying EGFR/PD-L1-targeting siRNAs without radiation pretreatment had a moderate effect on tumor growth and increased survival from 21 to 24 days.
Radiation pretreatment plus a siRNA-carrying nanoparticle without an effective guiding peptide also had a moderate effect on both tumor growth and survival.
Radiation pretreatment plus an iRGD-guided nanoparticle carrying the EGFR/PD-L1-targeting siRNAs had the greatest benefit, increasing survival to 38 days.

Examination of tissue from the tumor sites found that the combined therapy decreased expression of PD-L1 and increased recruitment of CD8 T cells, indicating an increased antitumor immune response.

An associate professor of Neurology at Harvard Medical School, Tannous explains that radiation is known to counteract the immunosuppressive glioblastoma microenvironment in several ways, suggesting a dual action of both increasing nanoparticle delivery and enhancing the antitumor immune response. While aspects such as the optimum dose and timing of radiation pretreatment have yet to be determined, he notes, the same approach could be used to treat other aggressive tumors with siRNAs targeting different molecular pathways.


Additional co-authors of the ACS Nano paper are Litia Carvalho, PhD, Tian Tian and Max Zinter, MGH Neuro-Oncology; Hasan Akbaba, PhD, and Ayse Gulten Kantarci, Ege University, Ismir, Turkey; Pierre Obeid, University of Balamand, Tripoli, Lebanon; E. Antonio Chiocca, MD, PhD, Brigham and Women's Hospital; and Ralph Weissleder, MD, PhD, MGH Center for Systems Biology. Support for the study includes National Cancer Institute grant P01 CA069246, National Institute for Neurological Disorders and Stroke grant P30 NS04776, and a Scientific and Technological Research Council of Turkey scholarship.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $925 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2018 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

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