The role of photodynamic therapy on multidrug resistant breast cancer

Abstract

Breast cancer heterogeneity allows cells with different phenotypes to co-exist, contributing to treatment failure and development of drug resistance. In addition, abnormal signal transduction and dysfunctional DNA repair genes are common features with breast cancer resistance. Chemo-resistance of breast cancer associated with multidrug resistance events utilizes ATP-binding cassette (ABC) efflux transporters to decrease drug intracellular concentration. Photodynamic therapy (PDT) is the treatment that involves a combination of a photosensitizer (PS), light and molecular oxygen to induce cell death. This treatment modality has been considered as a possible approach in combatting multidrug resistance phenomenon although its therapeutic potential towards chemo-resistance is still unclear. Attempts to minimize the impact of efflux transporters on drug resistance suggested concurrent use of chemotherapy agents, nanotechnology, endolysosomal release of drug by photochemical internalization and the use of structurally related compound inhibitors to block the transport function of the multidrug resistant transporters. In this review, we briefly summarize the role of membrane ABC efflux transporters in therapeutic outcomes and highlight research findings related to PDT and its applications on breast cancer with multidrug resistance phenotype. With the development of an ideal PS for photodynamic cancer treatment, it is possible that light activation may be used not only to sensitize the tumour but also to enable release of PS into the cytosol and as such bypass efflux membrane proteins and inhibit escape pathways that may lead to resistance.

Photodynamic Therapy in Primary Breast Cancer

“…We consider that future studies should focus first on the best way to deliver PDT (e.g., drug dose and targeting, light dose, multiple fibers). Much current PDT research focuses on looking for ways of increasing the selectivity of PDT between tumors and their organ of origin, such as linking photosensitizers to tumor-specific antibodies, the use of nano-carriers for photosensitizing drug delivery, the latter particularly in multidrug-resistant breast cancer, where the photodynamic effect may play a role in bypassing and inhibiting escape pathways [29][30][31]. However, we see the best potential of PDT in breast cancer in the multi-therapy setting in patients with a poor or incomplete response to NAT or in cases where NAT and surgery are not possible.…”

Green Synthesis of Yellow-fluorescent Carbon Nano-Dots for Cancer-Cell Image and Photocatalytic Inactivation by Using Microplasma

“…During PDT, cancer cells can be killed by cytotoxic ROS generated by the endocytosed photosensitizer under appropriate irradiation conditions [34,35]. ROS can inactivate target cells by apoptosis or necrosis with little side effects via PDT in several diseases [36][37][38][39]. Inspection of Figure 4A shows that ROS reagent emits red fluorescence, indicating the generation of ROS, which is well overlapped with the fluorescence of CQDs.…”

Role of Photoactive Phytocompounds in Photodynamic Therapy of Cancer

“…More than 300 chemical compounds have already been identified as potential candidates to be used as PSs. Amongst these, a few were authorised for clinical application in PDT, and others were medically evaluated, whereas some are still under examination [ 33 , 34 ]. We have tabulated some PSs which are used in various cancer treatments in Table 1 .…”

“…Photosensitisers are naturally or chemically produced compound conjugated with a visible light-absorbing chromophore group with a strong chemical absorbance. Choosing the correct PS is the most important phase in PDT for a successful outcome [ 33 , 34 ]. The purity and the presence of a tetrapyrrole structure with good storage stability are the preferable properties of most PSs used in PDT.…”

“…PDT’s cancer cell death mechanism starts after the activation of administrated PS by a specific wavelength of light. The PS’s hydrophilic, hydrophobic, and ionic charge-related interaction nature plays an important role in the targeting of particular cancer cell receptor (globulins and Low-Density Lipoprotein (LDL) receptors) [ 34 ]. After the activation of PSs, the cancer cell death mechanism might occur in three main pathways ( Figure 1 ), namely, apoptosis, necrosis, and autophagy [ 33 , 65 , 66 ].…”