Fischell Department of Bioengineering, University of Maryland, College Park, MD.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, North Carolina State University, Raleigh, NC.
Photochem Photobiol. 2020 Mar;96(2):232-259. doi: 10.1111/php.13209. Epub 2020 Mar 5.
Targeting the tumor microenvironment (TME) provides opportunities to modulate tumor physiology, enhance the delivery of therapeutic agents, impact immune response and overcome resistance. Photodynamic therapy (PDT) is a photochemistry-based, nonthermal modality that produces reactive molecular species at the site of light activation and is in the clinic for nononcologic and oncologic applications. The unique mechanisms and exquisite spatiotemporal control inherent to PDT enable selective modulation or destruction of the TME and cancer cells. Mechanical stress plays an important role in tumor growth and survival, with increasing implications for therapy design and drug delivery, but remains understudied in the context of PDT and PDT-based combinations. This review describes pharmacoengineering and bioengineering approaches in PDT to target cellular and noncellular components of the TME, as well as molecular targets on tumor and tumor-associated cells. Particular emphasis is placed on the role of mechanical stress in the context of targeted PDT regimens, and combinations, for primary and metastatic tumors.
靶向肿瘤微环境（TME）为调节肿瘤生理学、增强治疗剂的递送、影响免疫反应和克服耐药性提供了机会。光动力疗法（PDT）是一种基于光化学的非热方法，在光激活部位产生反应性分子物质，目前已用于非肿瘤和肿瘤的应用。PDT 所具有的独特机制和精确的时空控制能力使选择性调节或破坏 TME 和癌细胞成为可能。机械应激在肿瘤生长和存活中起着重要作用，对治疗设计和药物输送的影响越来越大，但在 PDT 及其基于 PDT 的组合中研究甚少。本文综述了 PDT 中靶向 TME 的细胞和非细胞成分以及肿瘤和肿瘤相关细胞上的分子靶点的药物工程和生物工程方法。特别强调了机械应力在针对原发性和转移性肿瘤的靶向 PDT 方案及其组合中的作用。
