" In some X-ray PDT implementations, scintillators and photosensitizers are delivered independently of one another. We also thank you for pointing out our accidental omission of X-PACT and have, accordingly, modified our manuscript at lines 546-553 (and added 2 references that are, temporarily, appended to the References section, pending editorial staff insertion/renumbering at line 553) to read: We truly hope our paper stimulates broader interest in, and appreciation of, this new and potentially paradigm shifting form of photodynamic therapy. We deeply appreciate your in-depth review of our manuscript and kind words of support. The mechanism: the X-ray exciting an Energy Modulator – rare earth oxide Energy Modulator absorbs X-Ray and emits UVA radiation in situ produced UVA excites co-administered psoralen (8-MOP), Psoralen activation generates anti-tumor response, resulting in cell apoptotic death. Very nice, very well written, a huge amount of data and references, I don't have anything else to say, except to add another Energy Down Converting Process Cascade, called XPACT (X-ray psoeral Activated Cancer Therapy, that works in the same way: the photosensitizer is a psoralen derivative. We hope our paper stimulates broader interest in, and appreciation of, this new and potentially paradigm shifting form of photodynamic therapy. This work is well written and could be accepted in its current form. examined the underlying principles and evolution of PDT: from its initial use of light activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of x-ray activated, scintillator-photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. In this manuscript, “X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy” by Souris et al. We too hope our paper stimulates broader interest in, and appreciation of, this new and potentially paradigm shifting form of photodynamic therapy. The work is certainly interesting and the subject can stimulate the attention of a large number of readers. Although there are still many studies to be done to optimize and customize the nanoplatform design for clinical application, this paper reports and clearly demonstrates that X-ray PDT could prove valuable for anticancer therapy both in association with radiotherapy and independently. biodistribution, biocompatibility, bioelimination and possible toxicity. None of the nanoplatforms have entered clinical use yet because further investigations are still needed to evaluate carefully. These nanoplatforms produce large amounts of ROS when irradiated with diagnostic x-ray doses and energies, and enable photodynamic therapy of deeper tissues without surgery or laparoscopy to reach those organs. This manuscript details the principles and evolution of photodynamic therapy starting from that which makes use of small molecule photosensitizers that are activated by light, to the recent development of X-ray activated hybrid scintillator-photosensitizer nanoplatforms that actively target biomarkers of the cancer.
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