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Dynamic tumor therapies (mainly including photodynamic therapy (PDT) and sonodynamic therapy (SDT)) offer new approaches to cancer treatment. They are often characterized by their noninvasive nature, high selectivity, and low toxicity. Sensitizers are crucial for dynamic therapy. Developing efficient sensitizers with good biocompatibility and controllability is an important aim in dynamic therapy. Porphyrins and metalloporphyrins attract great attention due to their excellent photophysical properties and low cytotoxicity under non-light. Compared to porphyrins, metalloporphyrins show greater potential for dynamic therapy due to their enhanced photochemical and photophysical properties after metal ions coordinate with porphyrin rings. This paper reviews some metalloporphyrin-based sensitizers used in photo/sonodynamic therapy and combined therapy. In addition, the probable challenges and bottlenecks in clinical translation are also discussed. [ABSTRACT FROM AUTHOR]

Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic Aliivibrio fischeri cells in the Microtox® test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115—melanoma, MRC-5—lung fibroblasts, and PHDF—primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: Candida albicans, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm2) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in Staphylococcus aureus survival of over 5.4 log. [ABSTRACT FROM AUTHOR]

Ruthenium(II) polypyridyl complexes are being tested as potential anticancer agents in different therapies, which include conventional chemotherapy and light-activated approaches. A mechanistic study on a recently synthesized dual-action Ru(II) complex [Ru(bpy)2(sora)Cl]+ is described here. It is characterized by two mono-dentate leaving ligands, namely, chloride and sorafenib ligands, which make it possible to form a di-aquo complex able to bind DNA. At the same time, while the released sorafenib can induce ferroptosis, the complex is also able to act as a photosensitizer according to type II photodynamic therapy processes, thus generating one of the most harmful cytotoxic species, 1O2. In order to clarify the mechanism of action of the drug, computational strategies based on density functional theory are exploited. The photophysical properties of the complex, which include the absorption spectrum, the kinetics of ISC, and the character of all the excited states potentially involved in 1O2 generation, as well as the pathway providing the di-aquo complex, are fully explored. Interestingly, the outcomes show that light is needed to form the mono–aquo complex, after releasing both chloride and sorafenib ligands, while the second solvent molecule enters the coordination sphere of the metal once the system has come back to the ground-state potential energy surface. In order to simulate the interaction with canonical DNA, the di-aquo complex interaction with a guanine nucleobase as a model has also been studied. The whole study aims to elucidate the intricate details of the photodissociation process, which could help with designing tailored metal complexes as potential anticancer agents. [ABSTRACT FROM AUTHOR]

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT. [ABSTRACT FROM AUTHOR]

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an effective method for treating microbial infections by leveraging the unique photophysical properties of photosensitizing agents, but issues such as fluorescence quenching and the restricted generation of reactive oxygen species (ROS) under hypoxic conditions still remain. In this study, we successfully synthesized and designed a coumarin-based aggregation-induced emission luminogen (AIEgen), called ICM, that shows a remarkable capacity for type I ROS and type II ROS generation. The 1O2 yield of ICM is 0.839. The ROS it produces include hydroxyl radicals (HO•) and superoxide anions (O2•−), with highly effective antibacterial properties specifically targeting Staphylococcus aureus (a Gram-positive bacterium). Furthermore, ICM enables broad-spectrum fluorescence imaging and exhibits excellent biocompatibility. Consequently, ICM, as a potent type I photosensitizer for eliminating pathogenic microorganisms, represents a promising tool in addressing the threat posed by these pathogens. [ABSTRACT FROM AUTHOR]

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer. [ABSTRACT FROM AUTHOR]

Perylenediimides (PDIs) are composed of a central perylene ring, on which are grafted two imide groups at the peri positions. Thionated PDIs are characterized by the substitution of one or more oxygen atoms of these imide functions with sulfur atoms. This structural modification alters the electronic properties with a redshift of the optical absorption accompanied by modification of the charge transport characteristics compared to their non-thionated counterparts. These properties make them suitable candidates for applications in optoelectronic devices, such as organic light-emitting diodes and organic photovoltaics. Moreover, the presence of sulfur atom(s) can favor the promotion of reactive oxygen species production for photodynamic and photothermal therapies. These thionated PDIs can be synthesized through the post-functionalization of PDIs by using a sulfurizing reagent. Nevertheless, the main drawbacks remain the difficulties in adjusting the degree of thionation and obtaining tri- and tetrathionated PDIs. Up to now, this thionation reaction has been described almost exclusively using Lawesson's reagent. In the current study, we present our first investigations into an alternative reagent to enhance selectivity and achieve a greater degree of thionation. The association of phosphorus pentasulfide with hexamethyldisiloxane (Curphey's reagent) clearly demonstrated higher reactivity compared with Lawesson's reagent to attain multi-thionated PDIs. [ABSTRACT FROM AUTHOR]

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer. [ABSTRACT FROM AUTHOR]

Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level. [ABSTRACT FROM AUTHOR]

The field of molecular cages has attracted increasing interest in relation to the development of biological applications, as evidenced by the remarkable examples published in recent years. Two key factors have contributed to this achievement: First, the remarkable and adjustable host–guest chemical properties of molecular cages make them highly suitable for biological applications. This allows encapsulating therapeutic molecules to improve their properties. Second, significant advances have been made in synthetic methods to create water-soluble molecular cages. Achieving the necessary water solubility is a significant challenge, which in most cases requires specific chemical groups to overcome the inherent hydrophobic nature of the molecular cages which feature the organic components of the cage. This can be achieved by either incorporating water-solubilizing groups with negative/positive charges, polyethylene glycol chains, etc.; or by introducing charges directly into the cage structure itself. These synthetic strategies allow preparing water-soluble molecular cages for diverse biological applications, including cages' anticancer activity, anticancer drug delivery, photodynamic therapy, and molecular recognition of biological molecules. In the review we describe selected examples that show the main concepts to achieve water solubility in molecular cages and some selected recent biological applications. [ABSTRACT FROM AUTHOR]

Gold nanoclusters (Au NCs) with bright emission and unique chemical reactivity characters have been widely applied for optical sensing and imaging. With a combination of surface modifications, effective therapeutic treatments of tumors are realized. In this review, we summarize the recently adopted biosensing and therapy events based on Au NCs. Homogeneous and fluorometric biosensing systems toward various targets, including ions, small molecules, reactive oxygen species, biomacromolecules, cancer cells, and bacteria, in vitro and in vivo, are presented by turn-off, turn-on, and ratiometric tactics. The therapy applications are concluded in three aspects: photodynamic therapy, photothermal therapy, and as a drug carrier. The basic mechanisms and performances of these systems are introduced. Finally, this review highlights the challenges and future trend of Au NC-based biosensing and therapy systems. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis(N-alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N-alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms (Zn-C8). [ABSTRACT FROM AUTHOR]

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Dynamic tumor therapies (mainly including photodynamic therapy (PDT) and sonodynamic therapy (SDT)) offer new approaches to cancer treatment. They are often characterized by their noninvasive nature, high selectivity, and low toxicity. Sensitizers are crucial for dynamic therapy. Developing efficient sensitizers with good biocompatibility and controllability is an important aim in dynamic therapy. Porphyrins and metalloporphyrins attract great attention due to their excellent photophysical properties and low cytotoxicity under non-light. Compared to porphyrins, metalloporphyrins show greater potential for dynamic therapy due to their enhanced photochemical and photophysical properties after metal ions coordinate with porphyrin rings. This paper reviews some metalloporphyrin-based sensitizers used in photo/sonodynamic therapy and combined therapy. In addition, the probable challenges and bottlenecks in clinical translation are also discussed.

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.

Photodynamic inactivation (PDI) is a highly effective treatment that can eliminate harmful microorganisms in a variety of settings. This study explored the efficacy of a curcumin-rich extract, Curcuma L., (Cur)- and essential oil component, trans-cinnamaldehyde, (Ca)-mediated PDI against Listeria monocytogenes ATCC 15313 (Lm) including planktonic cells and established biofilms on silicone rubber (Si), polytetrafluoroethylene (PTFE), stainless steel 316 (SS), and polyethylene terephthalate (PET). Applying Ca- and Cur-mediated PDI resulted in planktonic cell reductions of 2.7 and 6.4 log CFU/cm2, respectively. Flow cytometric measurements (FCMs) coupled with CFDA/PI and TOTO®-1 staining evidenced that Ca- doubled and Cur-mediated PDI quadrupled the cell damage. Moreover, the enzymatic activity of Lm cells was considerably reduced by Cur-mediated PDI, indicating its superior efficacy. Photosensitization also affected Lm biofilms, but their reduction did not exceed 3.7 log CFU/cm2. Cur-mediated PDI effectively impaired cells on PET and PTFE, while Ca-mediated PDI caused no (TOTO®-1) or only slight (PI) cell damage, sparing the activity of cells. In turn, applying Ca-mediate PDI to Si largely diminished the enzymatic activity in Lm. SS contained 20% dead cells, suggesting that SS itself impacts Lm viability. In addition, the efficacy of Ca-mediated PDI was enhanced on the SS, leading to increased damage to the cells. The weakened viability of Lm on Si and SS could be linked to unfavorable interactions with the surfaces, resulting in a better effect of Ca against Lm. In conclusion, Cur demonstrated excellent photosensitizing properties against Lm in both planktonic and biofilm states. The efficacy of Ca was lower than that of Cur. However, Ca bears potent antibiofilm effects, which vary depending on the surface on which Lm resides. Therefore, this study may help identify more effective plant-based compounds to combat L. monocytogenes in an environmentally sustainable manner. [ABSTRACT FROM AUTHOR]

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies. [ABSTRACT FROM AUTHOR]

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical–physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising. [ABSTRACT FROM AUTHOR]

The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the leaves of Camellia ptilosperma S. Y. Liang et Q. D. Chen led to the isolation of ten undescribed compounds, including six new triterpenes (1–6) and four new pheophorbide-related compounds (7–10). Meanwhile, the cytotoxic activity of the six triterpenes against six cancer cell lines was evaluated by MTT assay. Compound 2 showed potent cytotoxicity toward HepG2 cells with an IC50 value of 2.57 μM. Compounds 4 and 5 exhibited cytotoxicity against MDA-MB231 cells, with IC50 values of 11.31 and 5.52 μM, respectively. Additionally, the cytotoxicity of four new pheophorbides against these cancer cells was evaluated both in the presence and absence of light treatment. Compound 7 exhibited exceptional photocytotoxicity against Hela, MCF-7, and A549 cells, with IC50 values of 0.43 μM, 0.28 μM, and 0.92 μM, respectively. Compound 10 demonstrated significant photodynamic cytotoxic activity against BEL-7402 and HepG2 cells with IC50 values of 0.77 μM and 0.33 μM, respectively. The photodynamic antibacterial activity of 7–10 was also tested for S. aureus, E. coli, K. pneumoniae, and P. aeruginosa under direct illumination. Compounds 8 and 10 exhibited sensitivity to E. coli and demonstrated a photodynamic antibacterial effect, with a MIC value of 0.625 μM. [ABSTRACT FROM AUTHOR]

Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94–98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 μg/mL RB-nanoparticles, fluence ~126 J/cm2, and irradiance ~0.21 W/cm2). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications. [ABSTRACT FROM AUTHOR]

Tumor hypoxia, which is mainly caused by the inefficient microvascular systems induced by rapid tumor growth, is a common characteristic of most solid tumors and has been found to hinder treatment outcomes for many types of cancer therapeutics. In this study, an amphiphilic block copolymer, poly (ethylene glycol) methyl ether acrylate-block-n-butyl acrylate (PEGA-BA), was prepared via the ATRP method and self-assembled into core-shell micelles as nano radiosensitizers. These micelles encapsulated a photosensitizer, Chlorin e6 (Ce6), and demonstrated well-defined morphology, a uniform size distribution, and high oxygen loading capacity. Cell experiments showed that PEGA-BA@Ce6@PFCE micelles could effectively enter cells. Further in vitro anticancer studies demonstrated that the PEGA-BA@Ce6@PFCE micelles significantly suppressed the tumor cell survival rate when exposed to a laser. [ABSTRACT FROM AUTHOR]

Herein, pyridinium and 4-vinylpyridinium groups are introduced into the VIE-active N,N′-disubstituted-dihydrodibenzo[a,c]phenazines (DPAC) framework to afford a series of D-π-A-structured dihydrodibenzo[a,c]phenazines in consideration of the aggregation-benefited performance of the DPAC module and the potential mitochondria-targeting capability of the resultant pyridinium-decorated DPACs (DPAC-PyPF6 and DPAC-D-PyPF6). To modulate the properties and elucidate the structure–property relationship, the corresponding pyridinyl/4-vinylpyridinyl-substituted DPACs, i.e., DPAC-Py and DPAC-D-Py, are designed and studied as controls. It is found that the strong intramolecular charge transfer (ICT) effect enables the effective separation of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of DPAC-PyPF6 and DPAC-D-PyPF6, which is conducive to the generation of ROS. By adjusting the electron-accepting group and the π-bridge, the excitation, absorption, luminescence, photosensitizing properties as well as the mitochondria-targeting ability can be finely tuned. Both DPAC-PyPF6 and DPAC-D-PyPF6 display large Stokes shifts (70–222 nm), solvent-dependent absorptions and emissions, aggregation-induced emission (AIE), red fluorescence in the aggregated state (λem = 600–650 nm), aggregation-promoted photosensitizing ability with the relative singlet-oxygen quantum yields higher than 1.10, and a mitochondria-targeting ability with the Pearson coefficients larger than 0.85. DPAC-D-PyPF6 shows absorption maximum at a longer wavelength, slightly redder fluorescence and better photosensitivity as compared to DPAC-PyPF6, which consequently leads to the higher photocytotoxicity under the irradiation of white light as a result of the larger π-conjugation. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

Photodynamic therapy (PDT) is an innovative and perspective antineoplastic therapy. Tetra-α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) has shown antitumor activity in some tumor cells, but the manner in which caspase-1 is involved in the regulation of apoptosis and pyroptosis in the TαPcZn-PDT-treated breast cancer MCF-7 cells is unclear. Therefore, effects of TαPcZn-PDT on cytotoxicity, cell viability, apoptosis, pyroptosis, cellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), caspase-1, caspase-3, and nuclear transcription factor-κB (NFκB) in MCF-7 cells was firstly examined in the present study. The findings demonstrated that TαPcZn-PDT resulted in the increase in cytotoxicity and the percentage of apoptotic and pyroptotic cells, the reduction in cell viability and ΔΨm, the production of ROS and the activation of caspase-1, caspase-3 and NFκB in MCF-7 cells. Furthermore, the results also revealed that siRNA-targeting caspase-1 (siRNA-caspase-1) attenuated the effect of TαPcZn-PDT on apoptosis, pyroptosis and the activation of caspase-1, caspase-3 and NFκB in MCF-7 cells. Taken together, we conclude that caspase-1 regulates the apoptosis and pyroptosis induced by TαPcZn-PDT in MCF-7 cells. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising non-invasive approaches to cancer treatment. However, the development of multifunctional nanomedicines is necessary to enhance these approaches' effectiveness and safety. In this study, we investigated a polydopamine-based nanoparticle (PDA-ZnPc+ Nps) loaded with the efficient photosensitizer ZnPc(4TAP)12+ (ZnPc+) through in vitro and in vivo experiments to achieve synergistic PDT and PTT. Our results demonstrated that PDA-ZnPc+ Nps exhibited remarkable efficacy due to its ability to generate reactive oxygen species (ROS), induce photothermal effects, and promote apoptosis in cancer cells. Moreover, in both MCF-7 cells and MCF-7 tumor-bearing mice, the combined PDT/PTT treatment with PDA-ZnPc+ Nps led to synergistic effects. Subcellular localization analysis revealed a high accumulation of ZnPc+ in the cytoplasm of cancer cells, resulting in cellular disruption and vacuolation following synergistic PDT/PTT. Furthermore, PDA-ZnPc+ Nps exhibited significant antitumor effects without causing evident systemic damage in vivo, enabling the use of lower doses of photosensitizer and ensuring safer treatment. Our study not only highlights the potential of PDA-ZnPc+ Nps as a dual-functional anticancer agent combining PDA and PTT but also offers a strategy for mitigating the side effects associated with clinical photosensitizers, particularly dark toxicity. [ABSTRACT FROM AUTHOR]

Dendritic mesoporous organosilica nanoparticles (DMON) are a new class of biodegradable nanoparticles suitable for biomolecule delivery. We studied the photochemical internalization (PCI) and photodynamic therapy (PDT) of DMON to investigate new ways for DMON to escape from the endosomes-lysosomes and deliver biomolecules into the cytoplasm of cells. We added photosensitizers in the framework of DMON and found that DMON were loaded with siRNA or FVIII factor protein. We made four formulations with four different photosensitizers. The photosensitizers allowed us to perform imaging of DMON in cancer cells, but the presence of the tetrasulfide bond in the framework of DMON quenched the formation of singlet oxygen. Fortunately, one formulation allowed us to efficiently deliver proapoptotic siRNA in MCF-7 cancer cells leading to 31% of cancer cell death, without irradiation. As for FVIII protein, it was loaded in two formulations with drug-loading capacities (DLC) up to 25%. In conclusion, DMON are versatile nanoparticles capable of loading siRNA and delivering it into cancer cells, and also loading FVIII protein with good DLC. Due to the presence of tetrasulfide, it was not possible to perform PDT or PCI. [ABSTRACT FROM AUTHOR]

Cancer continues to pose a severe threat to global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in managing cancer, encounter considerable challenges, including drug resistance, poor drug solubility, and difficulties targeting tumors, specifically limiting their overall efficacy. Nanomedicine's application in cancer therapy signals a new epoch, distinguished by the improvement of the specificity, efficacy, and tolerability of cancer treatments. This review explores the mechanisms and advantages of nanoparticle-mediated drug delivery, highlighting passive and active targeting strategies. Furthermore, it explores the transformative potential of nanomedicine in tumor therapeutics, delving into its applications across various treatment modalities, including surgery, chemotherapy, immunotherapy, radiotherapy, photodynamic and photothermal therapy, gene therapy, as well as tumor diagnosis and imaging. Meanwhile, the outlook of nanomedicine in tumor therapeutics is discussed, emphasizing the need for addressing toxicity concerns, improving drug delivery strategies, enhancing carrier stability and controlled release, simplifying nano-design, and exploring novel manufacturing technologies. Overall, integrating nanomedicine in cancer treatment holds immense potential for revolutionizing cancer therapeutics and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Photodynamic therapy, an alternative that has gained weight and popularity compared to current conventional therapies in the treatment of cancer, is a minimally invasive therapeutic strategy that generally results from the simultaneous action of three factors: a molecule with high sensitivity to light, the photosensitizer, molecular oxygen in the triplet state, and light energy. There is much to be said about each of these three elements; however, the efficacy of the photosensitizer is the most determining factor for the success of this therapeutic modality. Porphyrins, chlorins, phthalocyanines, boron-dipyrromethenes, and cyanines are some of the N-heterocycle-bearing dyes' classes with high biological promise. In this review, a concise approach is taken to these and other families of potential photosensitizers and the molecular modifications that have recently appeared in the literature within the scope of their photodynamic application, as well as how these compounds and their formulations may eventually overcome the deficiencies of the molecules currently clinically used and revolutionize the therapies to eradicate or delay the growth of tumor cells. [ABSTRACT FROM AUTHOR]

Skin cancer is one of the cancers that registers the highest number of new cases annually. Among all forms of skin cancer, melanoma is the most invasive and deadliest. The resistance of this form of cancer to conventional treatments has led to the employment of alternative/complementary therapeutic approaches. Photodynamic therapy (PDT) appears to be a promising alternative to overcome the resistance of melanoma to conventional therapies. PDT is a non-invasive therapeutic procedure in which highly reactive oxygen species (ROS) are generated upon excitation of a photosensitizer (PS) when subjected to visible light of an adequate wavelength, resulting in the death of cancer cells. In this work, inspired by the efficacy of tetrapyrrolic macrocycles to act as PS against tumor cells, we report the photophysical characterization and biological assays of isobacteriochlorins and their corresponding chlorins and porphyrins against melanoma cancer cells through a photodynamic process. The non-tumoral L929 fibroblast murine cell line was used as the control. The results show that the choice of adequate tetrapyrrolic macrocycle-based PS can be modulated to improve the performance of PDT. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is recognized as a powerful method to inactivate cells. However, the photosensitizer (PS), a key component of PDT, has suffered from undesired photobleaching. Photobleaching reduces reactive oxygen species (ROS) yields, leading to the compromise of and even the loss of the photodynamic effect of the PS. Therefore, much effort has been devoted to minimizing photobleaching in order to ensure that there is no loss of photodynamic efficacy. Here, we report that a type of PS aggregate showed neither photobleaching nor photodynamic action. Upon direct contact with bacteria, the PS aggregate was found to fall apart into PS monomers and thus possessed photodynamic inactivation against bacteria. Interestingly, the disassembly of the bound PS aggregate in the presence of bacteria was intensified by illumination, generating more PS monomers and leading to an enhanced antibacterial photodynamic effect. This demonstrated that on a bacterial surface, the PS aggregate photo-inactivated bacteria via PS monomer during irradiation, where the photodynamic efficiency was retained without photobleaching. Further mechanistic studies showed that PS monomers disrupted bacterial membranes and affected the expression of genes related to cell wall synthesis, bacterial membrane integrity, and oxidative stress. The results obtained here are applicable to other types of PSs in PDT. [ABSTRACT FROM AUTHOR]

Selective photodynamic therapy (PDT) for cancer cells is more efficient and much safer. Most selective PDTs are realized by antigene-biomarker or peptide-biomarker interactions. Here, we modified dextran with hydrophobic cholesterol as a photosensitizer carrier to selectively target cancer cells, including colon cancer cells, and fulfilled selective PDT. The photosensitizer was designed with regular Aggregation-Induced Emission (AIE) units, including triphenylamine and 2-(3-cyano-4,5,5-trimethylfuran-2-ylidene)propanedinitrile. The AIE units can help to decrease the quenching effect in the aggregate state. The efficiency of the photosensitizer is further improved via the heavy atom effect after bromination modification. We found that the obtained photosensitizer nanoparticles could selectively target and ablate cancer cells after encapsulation into the dextran-cholesterol carrier. This study indicates that the polysaccharide-based carrier may have potential for cancer-targeting therapy beyond expectations. [ABSTRACT FROM AUTHOR]

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT. [ABSTRACT FROM AUTHOR]

With the increasing demand for tooth bleaching in esthetic dentistry, its safety has been the focus of a comprehensive body of literature. In this context, the aim of the present study was to evaluate the application effects of pentalysine β-carbonylphthalocyanine zinc (ZnPc(Lys)5)-mediated photodynamic therapy in dentin bleaching and its effects on dentin collagen. We first established a new and reproducible tooth staining model using dentin blocks stained by Orange II and then bleached with ZnPc(Lys)5 (25 μM) and hydrogen peroxide (10% or 30%). Data were analyzed with one- and two-way ANOVA and a significance level of p < 0.05. ZnPc(Lys)5 effectively bleached the dentin samples to an extent comparable to hydrogen peroxide at either 10% or 30% concentrations. Further studies on the dentin morphology, chemical element distribution, and protein constituents, using an electron microscope, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and SDS-PAGE, demonstrated that treatment with the photosensitizer preserved the dentin structure and, at the same time, the major organic component, collagen type I. For comparison, hydrogen peroxide (10% or 30%) treatment significantly degraded the collagen protein. This work indicated that the photosensitizer exerts potent bleaching effects on dentin staining; importantly, does not damage dentin and its collagen content; and opens up a new strategy to further explore various photosensitizers for the bleaching of both tooth enamel and dentin. [ABSTRACT FROM AUTHOR]

Cancer is threatening the survival of human beings all over the world. Phototherapy (including photothermal therapy (PTT) and photodynamic therapy (PDT)) and bioimaging are important tools for imaging–mediated cancer theranostics. Diketopyrrolopyrrole (DPP) dyes have received more attention due to their high thermal and photochemical stability, efficient reactive oxygen species (ROS) generation and thermal effects, easy functionalization, and tunable photophysical properties. In this review, we outline the latest achievements of DPP derivatives in cancer therapy and imaging over the past three years. DPP-based conjugated polymers and small molecules for detection, bioimaging, PTT, photoacoustic imaging (PAI)-guided PTT, and PDT/PTT combination therapy are summarized. Their design principles and chemical structures are highlighted. The outlook, challenges, and future opportunities for the development of DPP derivatives are also presented, which will give a future perspective for cancer treatment. [ABSTRACT FROM AUTHOR]

Energy transfer to ground state triplet molecular oxygen results in the generation of singlet molecular oxygen (1O2), which has potent oxidizing ability. Irradiation of light, notably ultraviolet A, to a photosensitizing molecule results in the generation of 1O2, which is thought to play a role in causing skin damage and aging. It should also be noted that 1O2 is a dominant tumoricidal component that is generated during the photodynamic therapy (PDT). While type II photodynamic action generates not only 1O2 but also other reactive species, endoperoxides release pure 1O2 upon mild exposure to heat and, hence, are considered to be beneficial compounds for research purposes. Concerning target molecules, 1O2 preferentially reacts with unsaturated fatty acids to produce lipid peroxidation. Enzymes that contain a reactive cysteine group at the catalytic center are vulnerable to 1O2 exposure. Guanine base in nucleic acids is also susceptible to oxidative modification, and cells carrying DNA with oxidized guanine units may experience mutations. Since 1O2 is produced in various physiological reactions in addition to photodynamic reactions, overcoming technical challenges related to its detection and methods used for its generation would allow its potential functions in biological systems to be better understood. [ABSTRACT FROM AUTHOR]

A series of tetraarylchlorins with 3-methoxy-, 4-hydroxy- and 3-methoxy-4-hydroxyphenyl meso-aryl rings (1-3-Chl) and their Sn(IV) complexes (1-3-SnChl) were synthesized and characterized so that their potential utility as photosensitizer dyes for use in photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) can be assessed. The photophysicochemical properties of the dyes were assessed prior to in vitro PDT activity studies against MCF-7 breast cancer cells through irradiation with Thorlabs 625 or 660 nm LED for 20 min (240 or 280 mW·cm−2). PACT activity studies were performed against both planktonic bacteria and biofilms of Gram-(+) S. aureus and Gram-(−) E. coli upon irradiation with Thorlabs 625 and 660 nm LEDs for 75 min. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.69−0.71 for 1-3-SnChl. Relatively low IC50 values between 1.1−4.1 and 3.8−9.4 µM were obtained for the 1-3-SnChl series with the Thorlabs 660 and 625 nm LEDs, respectively, during the PDT activity studies. 1-3-SnChl were also found to exhibit significant PACT activity against planktonic S. aureus and E. coli with Log10 reduction values of 7.65 and >3.0, respectively. The results demonstrate that the Sn(IV) complexes of tetraarylchlorins merit further in depth study as photosensitizers in biomedical applications. [ABSTRACT FROM AUTHOR]

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a non-invasive and effective approach used for cancer treatment, in which phototherapeutic agents are irradiated with an appropriate light source to produce cytotoxic reactive oxygen species (ROS) or heat to ablate cancer cells. Unfortunately, traditional phototherapy lacks a facile imaging method to monitor the therapeutic process and efficiency in real time, usually leading to severe side effects due to high levels of ROS and hyperthermia. To realize precise cancer treatment methods, it is highly desired to develop phototherapeutic agents possessing an imaging ability to evaluate the therapeutic process and efficacy in real time during cancer phototherapy. Recently, a series of self-reporting phototherapeutic agents were reported to monitor PDT and PTT processes by combining optical imaging technologies with phototherapy. Due to the real-time feedback provided by optical imaging technology, therapeutic responses or dynamic changes in the tumor microenvironment could be evaluated in a timely manner, thereby achieving personalized precision treatment and minimizing toxic side effects. In this review, we focus on the advances in the development of self-reporting phototherapeutic agents for a cancer phototherapy evaluation based on optical imaging technology to realize precision cancer treatments. Additionally, we propose the current challenges and future directions of self-reporting agents for precision medicine. [ABSTRACT FROM AUTHOR]

In this work we pursued research involving the microwave-assisted N-alkylation of a NH pyrrolidine-fused chlorin with methyl 4-(bromomethyl) benzoate and subsequent ester hydrolysis as a straightforward strategy to obtain carboxylic acid functionality in the pyrrolidine-fused chlorin, as a single reaction product. We studied the reaction's scope by extending the N-alkylation of the free-base chlorin and its corresponding Zn(II) complex to other alkyl halides, including 1,4-diiodobutane, N-(2-bromoethyl)phthalimide, and 2-bromoethanaminium bromide. In addition, two new chlorin–dansyl dyads were synthesized by reacting dansyl chloride with the 2-aminoethyl pyrrolidine-fused chlorin (dyad 6) and NH pyrrolidine-fused chlorin (dyad 7). According to spectral studies, the linker length between the two fluorophores influences the response of the dyads to the solvent polarity. Because of the simplicity of these approaches, we believe it will enable access to a vast library of custom-tailored N-functionalized chlorins while preserving their important absorption and emission spectra as photosensitizers in photodynamic therapy (PDT) of cancer and photodynamic inactivation (PDI) of microorganisms. [ABSTRACT FROM AUTHOR]

To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photosensitizers (PSs), the 3-(1′-(o-fluorobenzyloxy)ethyl pyropheophorbide and the corresponding meta-(m-) and para (p-) fluorinated analogs (methyl esters and carboxylic acids) were synthesized. Replacing iodine with fluorine in PSs did not make any significant difference in fluorescence and singlet oxygen (a key cytotoxic agent) production. The nature of the delivery vehicle and tumor types showed a significant difference in uptake and long-term cure by photodynamic therapy (PDT), especially in the iodinated PS. An unexpected difference in the pharmacokinetic profiles of fluorinated vs. iodinated PSs was observed. At the same imaging parameters, the fluorinated PSs showed maximal tumor uptake at 2 h post injection of the PS, whereas the iodinated PS gave the highest uptake at 24 h post injection. Among all isomers, the m-fluoro PS showed the best in vivo anti-cancer activity in mice bearing U87 (brain) or bladder (UMUC3) tumors. A direct correlation between the tumor uptake and PDT efficacy was observed. The higher tumor uptake of m-fluoro PS at two hours post injection provides a solid rationale for developing the corresponding 18F-agent (half-life 110 min only) for positron imaging tomography (PET) of those cancers (e.g., bladder, prostate, kidney, pancreas, and brain) where 18F-FDG-PET shows limitations. [ABSTRACT FROM AUTHOR]

A panchromatic light-absorbing [70]fullerene-perylene-BODIPY triad (C70-P-B) was synthesized and applied as a heavy atom-free organic triplet photosensitizer for photooxidation. The photophysical processes were comprehensively investigated by the methods of steady-state spectroscopy, time-resolved spectroscopy, as well as theoretical calculations. C70-P-B shows a strong absorption ability from 300–620 nm. Efficient cascading intramolecular singlet-singlet energy transfer in C70-P-B was confirmed by the luminescence study. The backward triplet excited state energy transfer from C70 moiety to perylene then occurs to populate 3perylene*. Thus, the triplet excited states of C70-P-B are distributed on both C70 and perylene moiety with lifetimes of 23 ± 1 μs and 175 ± 17 μs, respectively. C70-P-B exhibits excellent photooxidation capacity, and its yield of singlet oxygen reaches 0.82. The photooxidation rate constant of C70-P-B is 3.70 times that of C70-Boc and 1.58 times that of MB, respectively. The results in this paper are useful for designing efficient heavy atom-free organic triplet photosensitizers for practical application in photovoltaics, photodynamic therapy, etc. [ABSTRACT FROM AUTHOR]

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation. [ABSTRACT FROM AUTHOR]

The effect on the photophysical properties of sulfur- and selenium-for-oxygen replacement in the skeleton of the oxo-4-dimethylaminonaphthalimide molecule (DMNP) has been explored at the density functional (DFT) level of theory. Structural parameters, excitation energies, singlet–triplet energy gaps (ΔES-T), and spin–orbit coupling constants (SOC) have been computed. The determined SOCs indicate an enhanced probability of intersystem crossing (ISC) in both the thio- and seleno-derivatives (SDMNP and SeDMNP, respectively) and, consequently, an enhancement of the singlet oxygen quantum yields. Inspection of Type I reactions reveals that the electron transfer mechanisms leading to the generation of superoxide is feasible for all the compounds, suggesting a dual Type I/Type II activity. [ABSTRACT FROM AUTHOR]

Microbial infections have always been a thorny problem. Multi-drug resistant (MDR) bacterial infections rendered the antibiotics commonly used in clinical treatment helpless. Nanomaterials based on aggregation-induced emission luminogens (AIEgens) recently made great progress in the fight against microbial infections. As a family of photosensitive antimicrobial materials, AIEgens enable the fluorescent tracing of microorganisms and the production of reactive oxygen (ROS) and/or heat upon light irradiation for photodynamic and photothermal treatments targeting microorganisms. The novel nanomaterials constructed by combining polymers, antibiotics, metal complexes, peptides, and other materials retain the excellent antimicrobial properties of AIEgens while giving other materials excellent properties, further enhancing the antimicrobial effect of the material. This paper reviews the research progress of AIEgen-based nanomaterials in the field of antimicrobial activity, focusing on the materials' preparation and their related antimicrobial strategies. Finally, it concludes with an outlook on some of the problems and challenges still facing the field. [ABSTRACT FROM AUTHOR]

The intriguing properties of metal sulfide nanoparticles (=MxSy-NPs), particularly transition metal dichalcogenides, are discussed for their use in diverse biological applications. Herein, recent advances in MxSy-NPs-based imaging (MRI, CT, optical and photoacoustic) and phototherapy (photothermal and photodynamic) are presented. Also, recent made progress in the use of immuno-phototherapy combinatorial approaches in vitro and in vivo are reported. Furthermore, challenges in nanomaterials-based therapies and future research directions by applying MxSy-NPs in combinatorial therapies are envisaged. [ABSTRACT FROM AUTHOR]