Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

Abstract

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.

Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site

“…with lasers and light-emitting diode (LED) sources are classically used in perspective of skin rejuvenation, aiming at reducing wrinkles by stimulating a deposition of substantial amounts of collagens, which defeats the goal of improving nanotherapeutics delivery in the frame of cancer therapy. Photodynamic therapy (PDT) is a nonthermal therapeutic modality based on nontoxic photoactive photosensitiser molecules that spatiotemporally produce reactive molecular species such as reactive oxygen species (ROS) at the site of light irradiation[105]. The tumoricidal dose of ROS is only delivered after activation or 'turned on' when a certain kind of light irradiates the site of treatment and provoke tumour cell death by apoptosis or necrosis.…”

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress

“…PDT uses visible light to electronically excite a PS to generate RMS that are toxic to nearby targets [48,135,136]. The spatial and temporal control inherent to PDT has been leveraged to target various tumor compartments: (i) non-cellular stromal components (e.g., hyaluronic acid and collagen), (ii) stromal cells (e.g., fibroblasts), or (iii) tumor cells directly [137]. A limited set of studies have assessed PDT-related regimens in the context of physical stress in the tumor microenvironment [137,138].…”

“…The spatial and temporal control inherent to PDT has been leveraged to target various tumor compartments: (i) non-cellular stromal components (e.g., hyaluronic acid and collagen), (ii) stromal cells (e.g., fibroblasts), or (iii) tumor cells directly [137]. A limited set of studies have assessed PDT-related regimens in the context of physical stress in the tumor microenvironment [137,138]. PDT can help decrease solid stress and, thereby, modulate microenvironmental factors that influence tumor growth and treatment response, such as hypoxia and interstitial fluid pressure [139][140][141][142][143][144].…”

Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology

“…This approach has been in use for oncological treatments for several decades under the name of photodynamic therapy (PDT). Although PDT is well-established as a therapeutic treatment, there are serious disadvantages that still jeopardize the modality (Sorrin et al, 2020). Indeed, low actinic light penetration is cited as one of the severest (Fan et al, 2016).…”