The cationic porphyrin meso-tetra(4-[Formula: see text]-methylpyridyl)porphine (TMPyP) has a high yield of singlet oxygen generation upon light activation and a strong affinity for DNA. These advantageous properties have turned it into a promising photosensitizer for use in photodynamic therapy (PDT). In this review, we have summarized the current state-of-the-art applications of TMPyP for the treatment of cancer as well as its implementation in antimicrobial PDT. The most relevant studies reporting its pharmacokinetics, subcellular localization, mechanism of action, tissue biodistribution and dosimetry are discussed. Combination strategies using TMPyP-PDT together with other photosensitizers and chemotherapeutic agents to achieve synergistic anti-tumor effects and reduce resistance to therapy are also explored. Finally, we have addressed emerging applications of this porphyrin, including nanoparticle-mediated delivery, controlled drug release, biosensing and G-quadruplex stabilization for tumor growth inhibition. Altogether, this work highlights the great potential and versatility that TMPyP can offer in different fields of biomedicine such us cancer treatment or antimicrobial therapy.
Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment.
Pancreatic ductal adenocarcinoma remains one of the worst types of cancers mainly due to its late diagnosis, lack of effective therapies for advance disease and high chemoresistance. Novel therapeutic options that could improve patient quality of life and overall survival are therefore imperative. In this study, we describe the use of an original strategy based on photochemical internalisation (PCI) technology for pancreatic cancer treatment. Subcellular localisation of the photosensitiser meso-tetraphenylporphine-disulfonate (TPPS2a) was performed in PANC-1 cells, showing its preferential accumulation in lysosomes. Treatments with increasing concentrations of the ribosome-inactivating protein saporin or TPPS2a alone were compared with PCI-saporin. Metabolic activity and cell viability of PANC-1 cells were determined 96h post-illumination by MTT and trypan blue assays, respectively. Our results show that PCI using the photosensitiser TPPS2a, synergistically enhances the cytotoxic effects of saporin in PANC-1 cells and could offer more effective treatment options for pancreatic cancer.
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