Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. ...There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.
Photodynamic therapy (PDT) is a special form of phototherapy in which oxygen is needed, in addition to light and a drug called a photosensitiser (PS), to create cytotoxic species that can destroy ...cancer cells and various pathogens. PDT is often used in combination with other antitumor and antimicrobial therapies to sensitise cells to other agents, minimise the risk of resistance and improve overall outcomes. Furthermore, the aim of combining two photosensitising agents in PDT is to overcome the shortcomings of the monotherapeutic approach and the limitations of individual agents, as well as to achieve synergistic or additive effects, which allows the administration of PSs in lower concentrations, consequently reducing dark toxicity and preventing skin photosensitivity. The most common strategies in anticancer PDT use two PSs to combine the targeting of different organelles and cell-death mechanisms and, in addition to cancer cells, simultaneously target tumour vasculature and induce immune responses. The use of PDT with upconversion nanoparticles is a promising approach to the treatment of deep tissues and the goal of using two PSs is to improve drug loading and singlet oxygen production. In antimicrobial PDT, two PSs are often combined to generate various reactive oxygen species through both Type I and Type II processes.
This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on ...cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.
is an environmental bacterium, an opportunistic premise plumbing pathogen that causes the Legionnaires' disease.
presents a serious health hazard in building water systems, due to its high resistance ...to standard water disinfection methods. Our aim was to study the use of photodynamic inactivation (PDI) against
. We investigated and compared the photobactericidal potential of five cationic dyes. We tested toluidine blue (TBO) and methylene blue (MB), and three 3-
-methylpyridylporphyrins, one tetra-cationic and two tri-cationic, one with a short (CH
) and the other with a long (C
H
) alkyl chain, against
in tap water and after irradiation with violet light. All tested dyes demonstrated a certain dark toxicity against
; porphyrins with lower minimal effective concentration (MEC) values than TBO and MB. Nanomolar MEC values, significantly lower than with TBO and MB, were obtained with all three porphyrins in PDI experiments, with amphiphilic porphyrin demonstrating the highest PDI activity. All tested dyes showed increasing PDI with longer irradiation (0-108 J/cm
), especially the two hydrophilic porphyrins. All three porphyrins caused significant changes in cell membrane permeability after irradiation and
, co-cultivated with
after treatment with all three porphyrins and irradiation, did not recover in amoeba. We believe our results indicate the considerable potential of cationic porphyrins as effective anti-
agents.
The bacterium Legionella pneumophila is still one of the probable causes of waterborne diseases, causing serious respiratory illnesses. In the aquatic systems, L. pneumophila exists inside ...free-living amoebae or can form biofilms. Currently developed disinfection methods are not sufficient for complete eradication of L. pneumophila biofilms in water systems of interest. Photodynamic inactivation (PDI) is a method that results in an antimicrobial effect by using a combination of light and a photosensitizer (PS). In this work, the effect of PDI in waters of natural origin and of different hardness, as a treatment against L. pneumophila biofilm, was investigated. Three cationic tripyridylporphyrins, which were previously described as efficient agents against L. pneumophila alone, were used as PSs. We studied how differences in water hardness affect the PSs’ stability, the production of singlet oxygen, and the PDI activity on L. pneumophila adhesion and biofilm formation and in biofilm destruction. Amphiphilic porphyrin showed a stronger tendency for aggregation in hard and soft water, but its production of singlet oxygen was higher in comparison to tri- and tetracationic hydrophilic porphyrins that were stable in all water samples. All three studied porphyrins were shown to be effective as PDI agents against the adhesion of the L. pneumophila to polystyrene, against biofilm formation, and in the destruction of the formed biofilm, in their micromolar concentrations. However, a higher number of dissolved ions, i.e., water hardness, generally reduced somewhat the PDI activity of all the porphyrins at all tested biofilm growth stages.
Photodynamic therapy (PDT) is broadly used to treat different tumors, and it is a rapidly developing approach to inactivating or inhibiting the replication of fungi, bacteria, and viruses. Herpes ...simplex virus 1 (HSV-1) is an important human pathogen and a frequently used model to study the effects of PDT on enveloped viruses. Although many photosensitizers (PSs) have been tested for their antiviral properties, analyses are usually limited to assessing the reduction in viral yield, and thus the molecular mechanisms of photodynamic inactivation (PDI) remain poorly understood. In this study, we investigated the antiviral properties of TMPyP3-C
H
, a tricationic amphiphilic porphyrin-based PS with a long alkyl chain. We show that light-activated TMPyP3-C
H
can efficiently block virus replication at certain nM concentrations without exerting obvious cytotoxicity. Moreover, we show that the levels of viral proteins (immediate-early, early, and late genes) were greatly reduced in cells treated with subtoxic concentrations of TMPyP3-C
H
, resulting in markedly decreased viral replication. Interestingly, we observed a strong inhibitory effect of TMPyP3-C
H
on the virus yield only when cells were treated before or shortly after infection. In addition to the antiviral activity of the internalized compound, we show that the compound dramatically reduces the infectivity of free virus in the supernatant. Overall, our results demonstrate that activated TMPyP3-C
H
effectively inhibits HSV-1 replication and that it can be further developed as a potential novel treatment and used as a model to study photodynamic antimicrobial chemotherapy.
Summary
Photodynamic therapy (PDT) is becoming an evermore useful tool in oncology but is frequently limited by side‐effects caused by a lack of targeting of the photosensitizer. This problem can ...often be circumvented by the conjugation of photosensitizers to tumour‐specific monoclonal antibodies. An alternative is the use of single chain (sc) Fv fragments which, whilst retaining the same binding specificity, are more efficient at penetrating tumour masses because of their smaller size; and are more effectively cleared from the circulation because of the lack of an Fc domain. Here we describe the conjugation of two isothiocyanato porphyrins to colorectal tumour‐specific scFv, derived from an antibody phage display library. The conjugation procedure was successfully optimized and the resulting immunoconjugates showed no loss of cell binding. In vitro assays against colorectal cell lines showed these conjugates had a selective photocytotoxic effect on cells. Annexin V and propidium iodide staining of treated cells confirmed cell death was mediated principally via an apoptotic pathway. This work suggests that scFv : porphyrin conjugates prepared using isothiocyanato porphyrins show promise for use as targeted PDT agents.
•This review article covers an important emerging field – combining photodynamic sensitizers with radio and optical imaging agents to generate theranostic agents.•Key concepts are introduced such as: ...photophysics and photobiology of PDT, medical imaging and personalised medicine. These concepts lay the foundation as to what properties a new potential theranostic agent should possess.•A critical discussion of highlighted key developments in PET/PDT and PDT/NIR imaging is given.•Lastly, we have reviewed targeted 3rd generation porphyrin-based theranostic agents which show impressive pre-clinical potential.
This review summarises recent research into combining the photosensitizing properties of porphyrins with imaging techniques such as PET and NIR fluorescence for so called “theranostic” applications, which combine biomedical imaging and therapeutic potential into a single administered substance. The photophysical mechanisms of both the therapeutic and diagnostic properties of porphyrins are discussed, as well as key characteristics that are required in order to deliver the most effective treatment.
Sample displacement chromatography (SDC) in reversed phase and ion-exchange modes was introduced at the end of 1980s. This chromatographic method was first used for preparative purification of ...synthetic peptides, and subsequently adapted for protein fractionation, mainly in anion-exchange mode. In the past few years, SDC has been successfully used for enrichment of low- and medium-abundance proteins from complex biological fluids on both monolithic and bulk chromatographic supports. If aqueous mobile phase is used with the application of mild chromatographic conditions, isolated proteins are not denatured and can also keep their biological activity. In this paper, the use of SDC in anion-exchange mode on a high-capacity chromatographic resin for separation of proteins from complex biological mixtures such as human plasma is demonstrated. By use of three and more columns coupled in series during sample application, and subsequent parallel elution of detached columns, additional separation of bound proteins was achieved. Highly enriched human serum albumin fraction and a number of physiologically active medium- and low-abundance proteins could be fractionated and detected by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS). The use of the aforementioned columns that can be sanitized with 1 M sodium hydroxide for further application of SDC in biotechnology and food technology was discussed.
Display omitted
•Photophysical properties of two porphyrin photosensitizers studied.•Absorption and fluorescence spectra measured in different solvents.•Fluorescence decays measured by ...time-correlated single photon counting.•Optimized structures calculated at the TD-B3LYP/6-31++G(d,p) level of theory.•The triplet excited state lifetimes measured by laser flash photolysis.
The spectral and photophysical properties of two porphyrins, 5-(4-acetamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (1) and its Zn(II) complex 2 were investigated in different solvents by absorption, steady-state and time-resolved fluorescence spectroscopy, and laser flash photolysis. The findings were corroborated by computations at the TD-B3LYP/6-31++G(d,p) level of theory. The absorption spectra of 1 and 2 are the typical for porphyrins and their Zn complexes with the Soret bands at ≈ 420 nm and 430 nm, respectively, and the Q-bands at 515–650 nm, and 560–605 nm. Smaller differences in the absorption spectra compared to the symmetric porphyrins were assigned to more pronounced HOMO and HOMO-1 energy levels splitting in the asymmetric molecules. The temperature dependence of the absorption spectra with hypsochromic shifts suggests the formation of H-aggregates. The emission spectra are situated at 600–700 nm, and the vibronic resolution of the spectra for 1 depends on the solvent and the excitation wavelength, which was assigned due to the tautomerism by H-transfer within the porphyrin core. Quantum yields of fluorescence for 1 and 2 in methanolic solutions are Φf = 0.072 and 0.051, respectively. Although, the steady-state fluorescence spectra do not indicate that 1 and 2 form aggregates in methanolic and aqueous solutions (at <10-4 M), singlet decays measured by time-correlated single photon counting for both compounds were fit to multiexponential functions, which was explained by formation of aggregates in more concentrated solutions. Furthermore, at very high concentrations of 1 in CH3OH (>10-4 M), the dynamic formation of aggregates was evidenced by new bathochromically shifted band in the emission spectrum and the growth kinetics in the time-resolved fluorescence measurement. Triplet excited states of 1 and 2 were probed by laser flash photolysis. The triplets are populated with quantum yields of intersystem crossing, ΦISC = 0.34 and 0.41, respectively and lifetimes of the triplet excited states are in millisecond time-scale. Both triplets are quenched by O2 with the rate constants approaching diffusion limits. Relative quantum yields for the singlet oxygen formation are 0.86 and 0.92 respectively, rendering porphyrins 1 and 2 applicable for photodynamic therapy.
PDF
