Systemic antitumor immune response of doped yttria nanoscintillators under low-dose x-ray irradiation
Inadequate light penetration in tissues restricts photodynamic therapy to treating only superficial tumors. To enable x-ray-excited photodynamic therapy (XPDT) that targets deep-seated tumors, we synthesized a nanoscintillator-photosensitizer complex containing 5% Eu-doped Y<sub>2</sub>O<sub>3</sub> fluorescing at 611 nanometers and decorated with SiO<sub>2</sub> containing the scintillation-coupled photosensitizer methylene blue and a polyethylene glycol coating [PEGylated Y<sub>2</sub>O<sub>3</sub>:Eu@SiO<sub>2</sub>-methylene blue (pYSM)]. When irradiated, pYSMs generate singlet oxygen species in vitro, causing cytotoxicity with hallmarks of immunogenic cell death (calreticulin translocation to the cell membrane). Intravenously administered pYSMs home passively to pancreatic tumor xenografts and, upon 10 gray irradiation, cause significant tumor regression (<i>P</i> < 0.01). On combining XPDT with anti-PD1 immunotherapy, a distant nonirradiated tumor also regresses via an increase in intratumoral activated CD8<sup>+</sup> cytotoxic T cells. Collectively, we advance a systemically delivered XPDT strategy that mediates an antitumor effect in both irradiated and nonirradiated (abscopal) tumors when coupled with immunotherapy, converting an immunologically "cold" tumor to an immunologically "hot" tumor.
Authors
- Bhanu Prasad Venkatesulu (ORCID: https://orcid.org/0000-0003-2541-2055)
- Joseph Byung-Kyu Kim
- Holden R. Wagner (ORCID: https://orcid.org/0000-0001-8718-6474)
- Onur Sahin (ORCID: https://orcid.org/0000-0003-2191-5659)
- Guanhui Gao (ORCID: https://orcid.org/0000-0002-4760-1378)
- Okan Tezcan (ORCID: https://orcid.org/0000-0002-7704-7283)
- Sunil Krishnan (ORCID: https://orcid.org/0000-0002-1340-4771)
- Pulickel M. Ajayan
- Belal Abousaida (ORCID: https://orcid.org/0000-0001-5418-5221)
- Soumyabrata Roy (ORCID: https://orcid.org/0000-0003-3540-1341)
- Meiyazhagan Ashokkumar (ORCID: https://orcid.org/0000-0002-9765-4347)
- Rao V. Papineni (ORCID: https://orcid.org/0000-0002-1263-4292)
- Subhiksha Raghuram
- Pankaj K. Singh (ORCID: https://orcid.org/0000-0001-5299-2177)
- Valeria Gonzalez (ORCID: https://orcid.org/0000-0002-5747-1298)
- Yasmin Zahra (ORCID: https://orcid.org/0000-0003-4419-652X)
- Xiang Zhang (ORCID: https://orcid.org/0000-0003-4004-5185)
- Cheng‐En Hsieh (ORCID: https://orcid.org/0000-0002-2038-4537)
- Yuri Mackeyev (ORCID: https://orcid.org/0000-0003-4456-0563)
- Kristen A. Miller (ORCID: https://orcid.org/0000-0002-5694-3169)
- Sang Hyun Cho (ORCID: https://orcid.org/0000-0002-6357-5042)
- Geraldine V. Vijay
- P. S. FERNANDES (ORCID: https://orcid.org/0000-0002-3452-9661)
- Riaz Mowzoon-Mogharrabi (ORCID: https://orcid.org/0000-0003-3495-9968)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Bexley Hall (US)
- Jacksonville College (US)
- University of Kansas Medical Center (US)
- Connecticut Health Foundation (US)
- University of Pittsburgh Medical Center (US)
- Mayo Clinic in Florida (US)
- The University of Texas Health Science Center (US)
- Rice University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1126/sciadv.adr4008
- Citations
- 2
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 1.35