Shah Nimit, Squire John, Guirguis Mina, Saha Debabrata, Hoyt Kenneth, Wang Ken Kang-Hsin, Agarwal Vijay, Obaid Girgis
Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Cancers (Basel). 2022 Apr 15;14(8):2004. doi: 10.3390/cancers14082004.
With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies.
在过去二十年中，随着纳米材料的不断发展，专门的光纳米药物（光可激活纳米药物，PNMs）已逐渐演变为可被替代能源激发，这些替代能源通常比可见光能更深地穿透组织。这些能源包括位于可见近红外光谱之外的电磁辐射、高能粒子和声波等。各种直接激活机制利用了专门纳米材料的独特特性，如倍频、闪烁和放射增敏等，以及其他一些特性，以激活PNMs。其他间接激活机制则利用了深层穿透能源与组织相互作用的效应来激活近端PNMs。这些间接机制包括声致发光和切伦科夫辐射。这种直接和间接的深层组织激活在临床前环境中已被广泛探索，以促进深层组织抗癌光动力疗法（PDT）；然而，这些方法的临床转化尚未得到探索。本综述总结了PNMs深层组织激发的现状，并探讨了这种激发机制在临床应用中的可转化性。特别强调了如何重新利用当前的临床仪器，通过本综述中讨论的机制实现深层组织PDT，从而进一步加快这些极具前景的策略的转化。
