Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad up-date on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-on-going clinical trials.Metastatic lesions are usually multiple and resistant to conventional therapies, jeopardizing successful surgical resection, chemo and radiation treatment [4] .Light has been known to provide a therapeutic potential for several thousands of years. Over 3000 years ago, since the Ancient, Indian and Chinese civilizations it has been used for the treatment of various diseases [5] mainly in combination with reactive chemicals, for example to treat conditions like vitiligo, psoriasis and skin cancer [6] . After 1895 with the discovery of the phototherapy, which rendered Niels Ryberg Finsen the Nobel prize in Physiology/Medicine in 1903 in recognition of his work on the treatment of diseases, and in particular on the treatment of lupus vulgaris by means of concentrated light rays, many studies with the use of light and chemicals emerged [7] .Photodynamic therapy (PDT) is currently being used as an alternative treatment for the control of malignant diseases [8][9][10] . It is based in the uptake of a photosensitizer (PS) molecule which, upon being excited by light in a determined wavelength, reacts with oxygen and generates oxidant species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death [11,12] . PDT cytotoxic properties have been established to be due to the oxidation of a large range of biomolecules in cells, including nucleic acids, lipids, and proteins, leading to severe alteration in cell signaling cascades or in gene expression regulation [13,14] . Like all the newly proposed treatments, there is still place for improvements and lots of resources have been invested in this field recently. In this review, we set out to perform a broad up-date on PDT and it implication in cancer research and treatment. We have covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent reported preclinical studies and on-going clinical trials. PHOTOCHEMICAL PRINCIPLES AND COMPONENTS OF PDTAs previously stated, PDT involves the photosensitized oxidation of biomolecules which can be separated in two mechanisms. In Type I, light energy passes from exc...
Lack of effective treatments for aggressive breast cancer is still a major global health problem. We have previously reported that photodynamic therapy using methylene blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study, we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness and specificity towards tumor cells. Through lipidomics and biochemical approaches, we demonstrated that MB-PDT efficiency and specificity rely on polyunsaturated fatty acid-enriched membranes and on the better capacity to deal with photo-oxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results also pointed at a cross-talk between lysosome-dependent cell death (LDCD) and necroptosis induction after photo-oxidation, and contributed to broaden the understanding of MB-PDT-induced mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells.
Photodynamic therapy (PDT) appears as a promising alternative in the treatment of breast cancer since it can be highly effective in curing cancer while preserving normal tissue. However, predicting outcomes in PDT still constitutes a great challenge. One of the parameters that are usually empirically determined is the rate of photon flux delivered to the tissue (light fluence rate). In the present study, we intended to understand why monolayers of human cells derived from mammary adenocarcinomas (MDA‐MB‐231 and MCF‐7) respond quite differently to fluence rates (cells were irradiated either for 6 or for 16 min) at a fixed light dose (4.5 J cm−2) delivered with an array of LEDs in a typical methylene blue PDT protocol. While death rates of MDA‐MB‐231 cells were insensitive to the fluence rate, MCF‐7 cells showed a quite impressive (three times) decrease in cell death levels in the shorter irradiation protocol. Independent on cell type cell death was invariably correlated with the depletion of reduced glutathione intracellular levels and consequently with widespread redox misbalance. Our data show the potential to optimize fluence rates to provide exhaustion of the cell antioxidant responses in order to circumvent therapy resistance of breast tumors.
One challenge in point-of-care diagnostics is the lack of room-temperature methods for RNA detection based on enzymatic amplification and visualization steps. Here we perform a reverse transcription ligase chain reaction using our isothermal lesion induced DNA amplification (LIDA) technique that can be tuned to operate at any desired temperature. Using RNA-triggered LIDA, we can detect as little as ~100 attomoles target RNA and can distinguish RNA target from total cellular RNA. Finally, we demonstrate that the resulting DNA amplicons can be detected colorimetrically, also at room temperature, by rapid, targettriggered disassembly of DNA-modified gold nanoparticles. This integrated amplification/detection platform requires no heating or visualization instrumentation, which is an important step towards realizing instrument-free POC testing.
Photodynamic therapy (PDT) has been clinically applied to cure various diseases including cancer. Indeed, photophrin (porfimer sodium, Axcan Pharma, Montreal, Canada), a heterogenous mixture of porphyrins, was the first photosensitizer (PS) approved for the treatment of human bladder cancer in 1993 in Canada. Over the past 10 years the use of PDT in the treatment of benign and malignant lesions has increased dramatically. However, PDT is still considered as an adjuvant strategy due to its limitations, primarily including low tissue penetration by light and inaccurate lesion selectivity by the PSs. To overcome this scenario, new technologies and approaches including nanotechnology have been incorporated into the concept of PS formulations as PS delivery systems, as PSs per se or as energy transducers. The ideal nanophotosensitizer (NPS) for cancer therapy should possess the following characteristics: biocompatibility and biodegradability without toxicity, stability in physiological conditions, tumor specific targeting, strong near infrared absorption for efficient and sufficient light absorbance and large singlet oxygen quantum yield for PDT. To fulfill these requirements, several nanoscale delivery platforms and materials have been developed. In this review we will focus on the state of the art of nanotechnology contributions to the optimization of PDT as a therapeutic alternative to fight against cancer. For this purpose we will start from the basic concepts of PDT, discuss the versatility in terms of NPS formulations and how to tackle the deficiencies of the current therapy. We also give our critical view and suggest recommendations for improving future research on this area.
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