The role of photodynamic therapy in overcoming cancer drug resistance

Abstract

Many modalities of cancer therapy induce mechanisms of treatment resistance and escape pathways during chronic treatments, including photodynamic therapy (PDT). It is conceivable that resistance induced by one treatment might be overcome by another treatment. Emerging evidence suggests that the unique mechanisms of tumor cell and microenvironment damage produced by PDT could be utilized to overcome cancer drug resistance, to mitigate the compensatory induction of survival pathways and even to re-sensitize resistant cells to standard therapies. Approaches that capture the unique features of PDT, therefore, offer promising factors for increasing the efficacy of a broad range of therapeutic modalities. Here, we highlight key preclinical findings utilizing PDT to overcome classical drug resistance or escape pathways and thus enhance the efficacy of many pharmaceuticals, possibly explaining the clinical observations of the PDT response to otherwise treatment-resistant diseases. With the development of nanotechnology, it is possible that light activation may be used not only to damage and sensitize tumors but also to enable controlled drug release to inhibit escape pathways that may lead to resistance or cell proliferation.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…Moreover, there is no evidence for the development of resistance to PACT, and such resistance is considered highly improbable, because the oxidative stress in PACT is initiated by a PS that is usually present at multiple cellular sites (Tavares et al 2010;Maisch 2015). Similarly, PDT attacks tumours by causing oxidative damage to different cellular components, and even though there are some examples of resistance to PDT, evidence of resensitisation and synergy in chemoresistant tumour cell lines support the notion that PDT could play an important role in overcoming cancer drug resistance (Spring et al 2015).…”

Intracellular “activated” two-photon photodynamic therapy by fluorescent conveyor and photosensitizer co-encapsulating pH-responsive micelles against breast cancer

“…When the tumor volume reached 50-100 mm 3 , the mice were randomized into four groups: group 1, PBSinjection of PBS solution via the tail vein; group 2, laser only; group 3, PL TPA M -injection of PL TPA M intravenously without laser exposure; group 4, PL TPA M + laser -injection of PL TPA M via the tail vein and irradiation with an 808 nm laser at a power intensity of 0. …”

“…[1][2][3] However, most of the PSs applied in clinical settings belong to the porphyrin family, and these compounds are often limited by their poor water solubility. The extended delocalized aromatic π electron system of PS molecules leads to aggregation, which subsequently inhibits ROS generation.…”

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy

“…Therefore, photodynamic therapy (PDT) has emerged as an important therapeutic approach to treat cancer, infections, and other diseases (Almeida et al 2011, Alves et al 2015, Hamblin and Mroz 2008, Van Hillegersberg et al 1994, Spring et al 2015. This methodology combines the action of light at an appropriate wavelength to activate special drugs called photosensitizers (PS); in addition, the presence of an adequate amount of molecular oxygen in the tissue is also required (Van Hillegersberg et al 1994).…”