Complexing of ligands to photosensitizers (Ps) has gained popularity by enhancing solubility, cell-surface recognition and tissue specificity for applications in Photodynamic Therapy (PDT) and fluorescence-based diagnostics. Here we report on nine carbohydrate-functionalized porphyrazine (Pz-galactopyranose/methyl-ribose) derivatives bearing either H2 , Zn(II) or Ni(II) cores for potential use in PDT. Derivatives proved soluble only in organic solvents; dichloromethane (DCM) and tetrahydrofuran (THF). Derivatives were subsequently solubilized using DCM-based PEG-DSPE5000 -PBS encapsulation for biological studies due to THF cytotoxicity. Absorption spectra analyses viewed no correlation between core ion, carbohydrate type and peripheral position though encapsulation efficiency (%EE) followed a general order of Zn(II) (60-92%) > H2 (5-34%) > Ni(II) (4-21%). As such, phototoxicity of Zn(II)Pz derivatives were far superior to H2 Pz and Ni(II)Pz counterparts following 631.4 nm excitation of MCF-7 breast cancer cells. Variation was attributed to persistent aggregation and low %EE when regarding the absorption properties recorded. It is therefore believed that revision of the encapsulation method for H2 Pz and Ni(II)Pz derivatives would render improved phototoxicity. Zn(II)Pz derivatives show promise as agents for PDT of cancer.
Research within the field of photodynamic therapy has escalated over the past 20 years. The required conjunctional use of photosensitizers, particularly of the macrocycle structure, has lead to a vast repertoire of derivatives that branch classes and subclasses thereof. Each exhibits a differential range of physiochemical properties that influence their potential applications within the larger phototherapy field for use in either diagnostics, photodynamic therapy, both or none. Herein, we provide an overview of these properties as they relate to photodynamic therapy and to a lesser extent diagnostics. By summarizing the mechanistics of photodynamic therapy coupled to the photo-energetics displayed by macrocycle photosensitizers, we aimed to highlight the critical aspects any researcher should be aware of and consider when selecting and performing research for therapeutic application purposes. These include photosensitizer, photophysical and structural properties, synthesis design and subsequent attributes, main applications within research, common shortcomings exhibited and the current methods practiced to overcome them.
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Carcinogenesis occurs via mutation of critical genes conferring enhanced survival and protection to the ensuing tissue. Current therapies in use garner success due to their specificity for certain intracellular targets. This particularity, whist beneficial in identifying tumorigenic from normal tissue states, is limited by the variations in geno/phenotypic profiles displayed between tumor tissue types. As such, tissue-specific therapeutic combinations and adjuvants are often required for adequate effect, but present symptomatic complications and occasionally generate secondary carcinogenesis displaying multi-drug resistance (MDR). An accumulation of research over the recent years has suggested that photodynamic therapy (PDT) with macrocycle photosensitizers are a promising alternative. Its administration method and toxicity mechanism present attractive features for potentially overcoming MDR cancers of multiple tissue origins with limited symptomatic onsets. Herein, we highlight these potentials as referenced against existing therapeutics and consider the impact of macrocycle-PDT for broad spectrum application regardless of tumorigenic resistance profiles.
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