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In photodynamic therapy (PDT) treatment, heavy-atom-free photosensitizers (PSs) are a great source of singlet oxygen photosensitizer. Reactive oxygen species (ROS) are produced by an energy transfer from the lowest energy triplet excited state to the molecular oxygen of cancer cells. To clarify the photophysical characteristics in the excited states of a few experimentally identified thionated (>C=S) molecules and their oxygenated congeners (>C=O), a quantum chemical study is conducted. This study illustrates the properties of the excited states in oxygen congeners that render them unsuitable for PDT treatment. Concurrently, a hierarchy is presented based on the utility of the lowest-energy triplet excitons of thionated compounds. Their non-radiative decay rates are calculated for reverse-ISC and inter-system crossover (ISC) processes. In addition, the vibronic importance of C=O and C=S bonds is clarified by the computation of the Huang–Rhys factor, effective vibrational mode, and reorganization energy inside the Marcus–Levich–Jörtner system. ROS generation in thionated PSs exceeds their oxygen congeners as kf ≪ kISC, where radiative decay rate is designated as kf. As a result, the current work offers a calculated strategy for analyzing the effectiveness of thionated photosensitizers in PDT. [ABSTRACT FROM AUTHOR]

In this paper, we explore the molecular basis of combining photodynamic therapy (PDT), a light-triggered targeted anticancer therapy, with the traditional chemotherapeutic properties of the well-known cytotoxic agent gemcitabine. A photosensitizer prerequisite is significant absorption of biocompatible light in the visible/near IR range, ideally between 600 and 1000 nm. We use highly accurate multiconfigurational CASSCF/MS-CASPT2/MM and TD-DFT methodologies to determine the absorption properties of a series of gemcitabine derivatives with the goal of red-shifting the UV absorption band toward the visible region and facilitating triplet state population. The choice of the substitutions and, thus, the rational design is based on important biochemical criteria and on derivatives whose synthesis is reported in the literature. The modifications tackled in this paper consist of: (i) substitution of the oxygen atom at O2 position with heavier atoms (O → S and O → Se) to red shift the absorption band and increase the spin–orbit coupling, (ii) addition of a lipophilic chain at the N7 position to enhance transport into cancer cells and slow down gemcitabine metabolism, and (iii) attachment of aromatic systems at C5 position to enhance red shift further. Results indicate that the combination of these three chemical modifications markedly shifts the absorption spectrum toward the 500 nm region and beyond and drastically increases spin–orbit coupling values, two key PDT requirements. The obtained theoretical predictions encourage biological studies to further develop this anticancer approach. [ABSTRACT FROM AUTHOR]

[Display omitted] Non-invasive and efficient photodynamic therapy (PDT) holds great promise to circumvent resistance to traditional osteosarcoma (OS) treatments. Nevertheless, high-power PDT applied in OS often induces photothermogenesis, resulting in normal cells rupture, sustained inflammation and irreversible vascular damage. Despite its relative safety, low-power PDT fails to induce severe DNA damage for insufficient reactive oxygen species (ROS) production. Herein, a non-ROS-dependent DNA damage-sensitizing strategy is introduced in low-power PDT to amplify the therapeutic efficiency of OS, where higher apoptosis is achieved with low laser power. Inspired by the outstanding DNA damage performance of tannic acid (TA), TA-based metal phenolic networks (MPNs) are engineered to encapsulate hydrophobic photosensitizer (purpurin 18) to act as DNA damage-sensitized nanosynergists (TCP NPs). Specially, under low-power laser irradiation, the TCP NPs can boost ROS instantly to trigger mitochondrial dysfunction simultaneously with upregulation of DNA damage levels triggered by TA to reinforce PDT sensitization, evoking potent antitumor effects. In addition, TCP NPs exhibit long-term retention in tumor, greatly benefiting sustained antitumor performances. Overall, this study sheds new light on promoting the sensitivity of low-power PDT by strengthening DNA damage levels and will benefits advanced OS therapy. [ABSTRACT FROM AUTHOR]

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core–shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments. [ABSTRACT FROM AUTHOR]

Doping of polycyclic conjugated hydrocarbons (PCHs) with sulfur atoms is becoming more and more important as a means of creating unique functional materials. Recently, thiophene‐containing multiple helicenes have garnered enormous attention due to their intriguing electronic and (chir)optical properties compared with carbohelicenes. However, the efficient synthesis of thiopyran‐containing multiple helicenes and the underlying sulfur doping mechanisms are rather unexplored. Herein, the synthesis and structural analysis of a thiopyran‐containing double [7]helicene 3 are reported. X‐ray crystallographic analysis reveals 3 and its dication with C2‐symmetric propeller‐shape structures and compact interactions in the solid state. 3 exhibits deep‐red to near‐infrared (NIR) fluorescence emission. Tunable aromaticity of the central benzene ring and thiopyran rings is found by chemical oxidation, which is further confirmed by nucleus‐independent chemical shift (NICS), anisotropy of the induced current density (ACID) and harmonic oscillator model of aromaticity (HOMA) analysis. Furthermore, the chiral and photosensitizing characters of 3 are investigated. The excellent deep‐red to NIR fluorescence, circularly polarized luminescence (CPL) and photosensitizing activities suggest that 3 can be used as an outstanding photosensitizer in photodynamic therapy (PDT) and bioimaging, especially paving the way for future CPL‐PDT and CPL‐bio‐probe applications. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions. [ABSTRACT FROM AUTHOR]

Organic photosensitizers (PSs) can generate reactive oxygen species (ROS) via electron transfer (type I) and energy transfer (type II) pathways during photodynamic therapy (PDT). However, although numerous organic PSs have been constructed, the methods to optimize both type I and type II ROS generation are still not well explored. In this work, molecular engineering is applied to design three new organic PSs with varying triplet lifetimes and intersystem crossing (ISC) efficiency to achieve highly efficient type I&II ROS generation. The results reveal that after coated into nanoparticles (NPs) with DSPE‐PEG2000‐Biotin, the PS of mBDP‐PyH with the longest triplet lifetime and moderate ISC efficiency possesses good type II ROS and moderate type I ROS generation. With other properties being similar, the PS of mBDP‐2Py exhibits a shorter triplet lifetime, accompanied by concurrently reduced ROS generation for both types inside NPs. In contrast, the most potent PS of mBDP‐PyBr exhibits the shortest triplet lifetime but highly efficient ISC, with its NPs showing superior type I&II ROS generation. Moreover, both in vitro and in vivo experiments indicate that mBDP‐PyBr NPs display outstanding light toxicity under normoxic and hypoxic conditions. Overall, this study provides valuable guidance in designing effective organic PSs for PDT. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials, such as carbon quantum dots (CQDs), are excellent candidates for antibacterial agent development as they are cost-effective. Nitrogen-doped CQDs (N-doped CQDs) exhibit antibacterial activity against gram-positive bacteria. However, investigation of N-CQDs and their efficacy against the selected bacterial strains under visible light irradiation has not been carried out. Here, we aimed to evaluate N-CQDs for their efficacy as a photosensitizer for antimicrobial photodynamic therapy (aPDT). N-CQDs were synthesized using the hydrothermal method with 1,3,6-trinitropyrene (TNP) as the nitrogen and carbon source. Antimicrobial tests of N-CQDs were conducted against gram-positive (Bacillus subtilis NCIB 3610, Staphylococcus aureus Newman, and S. aureus USA300) and gram-negative (Escherichia coli K12) bacteria at different concentrations (0–100 mg/L). The N-CQDs exerted a moderate growth-inhibitory effect on gram-positive bacteria in the dark. However, in the presence of white light generated using 20-W light-emitting diode, N-CQDs could completely kill the bacteria at a low concentration of 20 mg/L. The minimal inhibitory concentration of N-CQDs for the two S. aureus strains (Newman and USA300) was 20 mg/L under light conditions, whereas that for B. subtilis was 100 mg/L. The results demonstrate that N-CQDs may be used as a photosensitizer in aPDT and as an antibacterial agent. [Display omitted] • Nitrogen-doped carbon quantum dots (N-CQDs) were produced by the hydrothermal method. • N-CQDs exerted moderate growth-inhibitory effect on gram-positive bacteria in dark. • Incubation with N-CQDs under the white light could completely kill the bacteria. • N-CQDs may be used as an antibacterial agent in antibacterial photodynamic therapy. [ABSTRACT FROM AUTHOR]

• This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. • This paper is the first of its kind to compile treatment options for women with HPV persistence and low-grade changes only. • Meta-analysis showed some therapies may lead to earlier HR-HPV resolution and CIN regression compared with natural clearance. In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression. We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool. 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance. This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. [ABSTRACT FROM AUTHOR]

High Epidermal growth factor receptor (EGFR) in Cutaneous Squamous Cell Carcinoma (cSCC) is associated with poor prognosis and advanced metastatic stages, severely impeding the efficacy of EGFR-targeting immunotherapy. This is commonly attributed to the combinatory outcomes of hypoxic tumor microenvironment (TME) and immunosuppressive effector cells together. Herein, a novel paradigm of EGFR-targeting oxygen-saturated nanophotosensitizers, designated as CHPFN-O 2 , has been specifically tailored to mitigate tumor hypoxia in EGFR-positive cSCC and achieve Cetuximab (CTX) - mediated immunotherapy (CIT). The conjugated CTX in CHPFN-O 2 serves to initiate immune responses by recruiting Fc receptor (FcR)-expressing immune effector cells towards tumor cells, thereby eliciting antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent cellular cytotoxicity (ADCC). Besides, CHPFN-O 2 can engender a shift from a tumor-friendly to a tumor-hostile one through improved tumor oxygenation, contributing to oxygen-elevated photodynamic therapy (oxPDT). Notably, the combination of oxPDT and CIT eventually promotes T-cell-mediated antitumor activity and successfully inhibits the growth of EGFR-expressing cSCC with good safety profiles. This comprehensive oxPDT/CIT integration aims not only to enhance therapeutic efficacy against EGFRhigh cSCC but also to extend its applicability to other EGFRhigh malignancies, thus delineating a new avenue for the highly efficient synergistic treatment of EGFR-expressing malignancies. EGFR-targeting oxygen-saturated nanophotosensitizers are meticulously designed to improve tumor selectivity, alleviate tumor hypoxia, reverse tumor immunosuppression, and recruit immune effector cells, thus resulting in the synergy of Cetuximab-based immunotherapy (CIT) and oxygen-elevated photodynamic therapy (oxPDT) for remarkably enhancing T cell-mediated antitumor efficacy against EGFR-expressing cSCC with great clinical value. [Display omitted] • CHPFN-O 2 demonstrates promising antitumor activity and high biosafety. • CHPFN-O 2 alleviates tumor hypoxia and initiates CIT-mediated immune responses. • CHPFN-O 2 presenting a new treatment paradigm of synergistic oxPDT/CIT. • CHPFN-O 2 improves the tumor microenvironment of EGFR-expressing cSCC. • The clinical prospects of CHPFN-O 2 can be extended to other forms of cSCC. [ABSTRACT FROM AUTHOR]

An imine-based nanoscale COF has been synthesized and functionalized with a pyridone-derived structure to create a singlet oxygen-storing nanoplatform, which can continuously produce and release singlet oxygen to realize "afterglow" photodynamic therapy. [Display omitted] Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen (1O 2) by fractionated generation is an effective approach to improve the efficacy of PDT. Herein, an imine-based nanoscale COF (TpDa-COF) has been synthesized and functionalized with a pyridone-derived structure (Py) to create a 1O 2 -storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1O 2. Under 660 nm laser exposure, Py interacts with 1O 2 produced by the porphyrin motif in COF backbones to generate 1O 2 -enriched COF (TpDa-COF@Py + hv), followed by the release of 1O 2 through retro -Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1O 2 upon laser exposure leads to an "afterglow" effect and a prolonged 1O 2 lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC 50) of 0.54 µg/mL on 4T1 cells. Remarkably, the Py-mediated TpDa-COF@Py nanoplatform demonstrates enhanced cell-killing capability under laser exposure, attributed to the sustained 1O 2 cycling, compared to TpDa-COF alone. Further in vivo assessment highlights the potential of TpDa-COF@Py + hv as a promising strategy to enhance phototheronostics and achieve effective tumor regression. Accordingly, the study supplies a generalized 1O 2 "afterglow" nanoplatform to improve the effectiveness of PDT. [ABSTRACT FROM AUTHOR]

Different types of photosensitizers (PSs) have different dynamics and intensities of accumulation, depending on the type of tumor or different areas within the same tumor. This determines the effectiveness of fluorescence diagnostics and photodynamic therapy (PDT). This paper studies the processes of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) and chlorin e6 (Ce6) accumulation in the central and border zones of a tumor after combined administration of two PSs into the patient's body. Fluorescence diagnostic methods have shown that sublingual administration of 5-ALA leads to the more intense accumulation of PpIX in a tumor compared to oral administration. Differences have been identified in the dynamics of 5-ALA-induced PpIX and Ce6 accumulation in the central and border zones of the tumor, as well as normal tissues. Ce6 accumulates mainly in the central zone of the tumor while PpIX accumulates in the border zone of the tumor. All patients with combined PDT experienced complete therapeutic pathomorphosis and relapse-free observation. [ABSTRACT FROM AUTHOR]

The lack of precise spatiotemporal gene modulation and therapy impedes progress in medical applications. Herein, a 980 nm near‐infrared (NIR) light‐controlled nanoplatform, namely URMT, is developed, which can allow spatiotemporally controlled photodynamic therapy and trigger the enzyme‐activated gene expression regulation in tumors. URMT is constructed by engineering an enzyme‐activatable antisense oligonucleotide, which combined with an upconversion nanoparticle (UCNP)‐based photodynamic nanosystem, followed by the surface functionalization of triphenylphosphine (TPP), a mitochondria‐targeting ligand. URMT allows for the 980 nm NIR light‐activated generation of reactive oxygen species, which can induce the translocation of a DNA repair enzyme (namely apurinic/apyrimidinic endonuclease 1, APE1) from the nucleus to mitochondria. APE1 can recognize the basic apurinic/apyrimidinic (AP) sites in DNA double‐strands and perform cleavage, thereby releasing the functional single‐strands for gene regulation. Overall, an augmented antitumor effect is observed due to NIR light‐controlled mitochondrial damage and enzyme‐activated gene regulation. Altogether, the approach reported in this study offers high spatiotemporal precision and shows the potential to achieve precise and specific gene regulation for targeted tumor treatment. [ABSTRACT FROM AUTHOR]

This study investigated the synthesis and application of cerium oxide/conjugated polymer (CeO2/CP) heterostructures for dual-modal phototherapy with a focus on antibacterial applications. CeO2 nanoparticles were synthesized via a precipitation method and combined with a conjugated polymer, polythiophene, in a 40/60 wt% ratio to form a composite that leveraged the photothermal properties of CeO2 and the photodynamic capabilities of the polymer. The composite was analyzed with Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), and UV-visible spectroscopy. Its photothermal efficiency and reactive oxygen species (ROS) generation were assessed under near-infrared (NIR) irradiation. Antibacterial tests against E. coli and MRSA demonstrated significant growth inhibition, particularly under elevated temperatures and repeated NIR irradiation cycles. The findings suggested that the CeO2/CP composite provided enhanced photothermal and photodynamic therapy, showing potential for effective use in medical applications aimed at infection control and enhanced tissue repair. [ABSTRACT FROM AUTHOR]

Global mortality data indicates cancer as the second-leading cause of death worldwide. Therefore, there's a pressing need to innovate effective treatments to address this significant medical and societal challenge. In recent years, X-ray-induced photodynamic therapy (X-PDT) has emerged as a promising advancement, revolutionizing traditional photodynamic therapy (PDT) for deeply entrenched malignancies by harnessing penetrating X-rays as external stimuli. Recent developments in X-ray photodynamic therapy have shown a trend toward minimizing radiation doses to remarkably low levels after the proof-of-concept demonstration. Early detection and real-time monitoring are crucial aspects of effective cancer treatment. Sophisticated X-ray imaging techniques have been enhanced by the introduction of X-ray luminescence nano-agents, alongside contrast nanomaterials based on X-ray attenuation. X-ray luminescence-based in vivo imaging offers excellent detection sensitivity and superior image quality in deep tissues at a reasonable cost, due to unhindered penetration and unimpeded auto-fluorescence of X-rays. This review emphasizes the significance of X-ray responsive theranostics, exploring their mechanism of action, feasibility, biocompatibility, and promising prospects in imaging-guided therapy for deep-seated tumors. Additionally, it discusses promising applications of X-PDT in treating breast cancer, liver cancer, lung cancer, skin cancer, and colorectal cancer. [ABSTRACT FROM AUTHOR]

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O2•‐) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced. [ABSTRACT FROM AUTHOR]

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O2•‐) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To test the prognostic role of anterior scleral substantia propria (ASSP) thickness in predicting the 3‐month response after half‐dose photodynamic therapy (PDT) in central serous chorioretinopathy (CSCR) and to assess its clinical relevance of ASSP in different CSCR phenotypes.A prospective, exploratory, multi‐centre cohort study conducted at IRCCS San Martino Hospital (Genoa, Italy) and Jules‐Gonin Eye Hospital (Lausanne, Switzerland). Demographic and clinical data, and optical coherence tomography (OCT) were collected at baseline and 3 months after PDT. Based on OCT images, we categorized CSCR phenotypes and collected clinically relevant imaging metrics. ASSP thickness was obtained from four different measurements using anterior segment (AS) OCT. Multivariable regression models were performed to evaluate the distribution of ASSP thicknesses among different CSCR phenotypes and to test the prognostic role of ASSP thickness in discriminating between PDT responders (complete subretinal fluid reabsorption) and partial responders.The study cohort comprised 109 Caucasian patients (82 males, 75.2%) with a total of 142 eyes: 84 eyes simple (59.1%) versus 58 eyes complex (40.9%) CSCR. A linear normal model confirmed a positive association between complex CSCR and higher ASSP thickness (β = 26.1, 95% CL = 12.1/40.1, p < 0.001), with a low prevalence of ciliochoroidal effusion loculations in AS‐OCT (1/142 eyes, 0.7%). ASSP thickening was positively linked to the presence of posterior cystoid retinal degeneration (PCRD; p = 0.002), indicating a potential role in the pathogenesis of severe CSCR phenotypes. In the subgroup of treated patients (61 eyes), 63.9% had a complete response after PDT. In these patients a logistic binary model highlighted a significantly higher risk of PDT non‐responsiveness (OR = 9.62, 95% CL = 2.44/37.9, p = 0.001) associated with a 60‐unit increase in ASSP thickness levels. By contrast, other anatomical parameters (i.e., body surface area, age, gender, axial length) showed no remarkable prognostic roles.This research highlighted the association of ASSP thickening with complex CSCR phenotype in Caucasian patients and its role in predicting PDT efficacy. These findings enhance our comprehension of the anatomical risk factors in patients affected with CSCR and potentially guide a better understanding of non‐responsive cases to PDT treatment. [ABSTRACT FROM AUTHOR]

Tumor‐specific activatable long‐wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH‐activatable cyanine‐based LW PSs (LET‐R, R = H, Cl, Br, I), among which the activated LET‐I exhibits strong light absorption at 808 nm and a remarkable 3.2‐fold enhancement in Φ1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual‐modal imaging‐escorted complete photodynamic eradication of tumors by the folic acid (FA)‐modified LET‐I probe (LET‐I‐FA), under the ultralow 808 nm laser power density (0.2 W cm−2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT. [ABSTRACT FROM AUTHOR]

Tumor‐specific activatable long‐wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH‐activatable cyanine‐based LW PSs (LET‐R, R = H, Cl, Br, I), among which the activated LET‐I exhibits strong light absorption at 808 nm and a remarkable 3.2‐fold enhancement in Φ1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual‐modal imaging‐escorted complete photodynamic eradication of tumors by the folic acid (FA)‐modified LET‐I probe (LET‐I‐FA), under the ultralow 808 nm laser power density (0.2 W cm−2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT. [ABSTRACT FROM AUTHOR]

Among various cancer treatment methods, photodynamic therapy has received significant attention due to its non-invasiveness and high efficiency in inhibiting tumour growth. Recently, specific organelle targeting photosensitizers have received increasing interest due to their precise accumulation and ability to trigger organelle-mediated cell death signalling pathways, which greatly reduces the drug dosage, minimizes toxicity, avoids multidrug resistance, and prevents recurrence. In this review, recent advances and representative photosensitizers used in targeted photodynamic therapy on organelles, specifically including the endoplasmic reticulum, Golgi apparatus, mitochondria, nucleus, and lysosomes, have been comprehensively reviewed with a focus on organelle structure and organelle-mediated cell death signalling pathways. Furthermore, a perspective on future research and potential challenges in precision photodynamic therapy has been presented at the end. [ABSTRACT FROM AUTHOR]

This study evaluates the efficacy of photodynamic therapy (PDT) in treating central serous chorioretinopathy (CSC) based on the number of engorged vortex vein draining macula visualized on ultra-widefield (UWF) indocyanine green angiography (ICGA). Thirty-six eyes of 36 patients with treatment-naïve CSC were included. Macula-draining vortex veins were assessed in each quadrant using UWF ICGA. The resolution of subretinal fluid (SRF), pigment epithelial detachment (PED), ellipsoid zone (EZ) disintegrity, and retinal pigment epithelium (RPE) irregularity were evaluated at 3 months after PDT. Visual and anatomical improvements were monitored for 12 months. Logistic regression analysis was performed to identify factors associated with poor visual outcomes. A higher number of macula-draining vortex vein was associated to persistent SRF (p = 0.004), PED (p = 0.001), EZ disintegrity (p = 0.011), and RPE irregularity (p = 0.001). Macula-draining vortex veins were also correlated with poor EZ restoration and limited best corrected visual acuity (BCVA) improvements. In multivariate analysis, the number of macula-draining vortex vein (B = 0.197, p = 0.047) was a risk factor for worse BCVA at 12 months. Increased macula-draining vortex vein was related with unfavorable anatomical and poor visual outcomes after PDT in CSC patients. [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. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSAn iron oxide nanosystem (Fe3O4Nps) encapsulated with chitosan under the adsorption of hexadecafluorozinc phthalocyanine (ZnPcP16) was developed. The synthesis of Fe3O4Nps was carried out through coprecipitation, followed by coating the nanoparticles with chitosan and incorporation with ZnPcP16. To understand and describe the mechanism of action of Fe3O4Nps-Chitosan-ZnPcP16, we use a variety of physicochemical characterization approaches. Electron microscopy results confirmed the monodispersity of the nanoparticles (13.2 ± 2.3 nm). Size distribution and surface charge (zeta potential) were determined by a dynamic light scattering (DLS) analyzer. VSM measurements confirmed its magnetic properties (1.18 emu.g−1). XDR confirmed the crystalline nature of the nanoparticles. UV-visible absorption and fluorescence spectra were used to evaluate the photophysical behavior of ZnPcP16 and Fe3O4Nps-Chitosan-ZnPcP16. These studies have demonstrated good results through synthesizing Fe3O4Nps-Chitosan-ZnPcP16, which could be a promising candidate for applications in photodynamic therapy.The photosensitizer was used for the first time for incorporation into magnetite nanoparticles.Fluorescence stability is observed using the Fe3O4Nps-Chitosan-ZnPcP16 nanoparticle for PDT.Nanoparticles based on Fe3O4Nps-Chitosan loaded with ZnPcPc16 showed photodynamic activity. [ABSTRACT FROM AUTHOR]

Ovarian cancer, often referred to as the "silent killer," is notoriously difficult to detect in its early stages, leading to a poor prognosis for many patients. Diagnosis is often delayed until the cancer has advanced, primarily due to its ambiguous and frequently occurring clinical symptoms. Ovarian cancer leads to more deaths than any other cancer of the female reproductive system. The main reasons for the high mortality rates include delayed diagnosis and resistance to treatment. As a result, there is an urgent need for improved diagnostic and treatment options for ovarian cancer. The standard treatments typically involve debulking surgery along with platinum-based chemotherapies. Among patients with advanced-stage cancer who initially respond to current therapies, 50-75% experience a recurrence. Recently, immunotherapy-based approaches to enhance the body's immune response to combat tumor growth have shown promise. Immune checkpoint inhibitors have shown promising results in treating other types of tumors. However, in ovarian cancer, only a few of these inhibitors have been effective because the tumor's environment suppresses the immune system and creates barriers for treatment. This hampers the effectiveness of existing immunotherapies. Nonetheless, advanced immunotherapy techniques and delivery systems based on nanotechnology hold promise for overcoming these challenges. [ABSTRACT FROM AUTHOR]

Homogeneous distribution and adequate accumulation of photosensitizer in tumor are essential for effective photodynamic therapy (PDT). However, the intricate tumor microenvironment (TME) often poses great challenges to the deep penetration and retention of therapeutic agents in tumor. Moreover, the important effect of PDT to induce specific antitumor immune response is impeded by multiple immunosuppressive mechanisms within TME. Confronting these issues, here a rationally designed nanosystem (SUN‐NPA) with acid‐responsive sphere‐to‐fiber transformation ability by leveraging the characters of drug molecules is proposed to achieve self‐delivery of photosensitizer Chlorin e6 (Ce6) and two small‐molecule immunomodulators, metformin (MET) and sunitinib (SUN). The spatiotemporal controlled transformation enables homogeneous distribution and high accumulation of drugs to achieve enduring PDT and complete tumor elimination. Meanwhile, the co‐delivered MET and SUN alleviate tumor immunosuppression from multiple aspects, effectively synergizing with PDT to ignite potent host immune response and long‐lasting immunological memory against tumor cells. The artful integration of enhanced PDT and activated antitumor immunity realized by SUN‐NPA leads to the significant inhibition of tumor growth and metastasis, exhibiting great potential for oncotherapy. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Photodynamic therapy (PDT) has been attracted a surge of research interest. However, there are several obstacles to limit the efficacy of PDT, such as hypoxic tumor microenvironment (TME), overexpressed glutathione (GSH), inefficient reactive oxygen species (ROS) generation, and so on. Herein, a smart responsive nanosystem was constructed, which was composed of Au25 modified with triphenylphosphine (Au25‐TPP), catalase (CAT) and GSH‐responsive diselenide‐bridged mesoporous silica nanoparticles (Se‐MSN). When the nanosystem arrived at tumor site, Se‐MSN was degraded by the intracellular overexpressed GSH to release Au25‐TPP and CAT. The Au25‐TPP was targeted to mitochondria and generated ROS under the 808 nm NIR laser irradiation to kill tumor cells. Simultaneously, CAT could catalyze hydrogen peroxide to provide oxygen for relieving the hypoxia of TME. Besides, GSH was consumed by the diselenide bond to diminish the ROS loss. The above tactics (mitochondria targeting, hypoxia relieving and GSH consuming) jointly enhanced the PDT efficacy. The nanosystem showed distinct in vitro anticancer effect significantly stronger than other groups containing one or two assistance. Moreover, the in vivo results suggested that the tumors could be restrained obviously. The current study provides a new inspiration for constructing novel inorganic nanomedicines with multiple enhancement effect of PDT efficacy. [ABSTRACT FROM AUTHOR]

[Display omitted] Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (B BR) and epigallocatechin gallate (E GCG) from natural plant extracts, named as BE NPs , which is successively coated with manganese dioxide nanoshells (M nO 2 NSs) and glucose oxidase (G OX) to form the final BEMG NPs. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMG NPs to produce gluconic acid and hydrogen peroxide (H 2 O 2). That is subsequently to decompose MnO 2 NSs in the BEMG NPs to generate oxygen (O 2). The BEMG NPs as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O 2. Under the synergistic function of the cascaded reaction, the BEMG NPs present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients. [ABSTRACT FROM AUTHOR]

The research on actinobacteria isolated from traditional medicinal plants is limited. Here, four new Streptomyces isolates (Ha1, Pp1, UzK and UzM) were obtained from the rhizospheres of Helianthus annuus, Pongamia pinnata and Ziziphus mauritiana, frequently utilized in Indian traditional medicine. The Streptomyces isolates aqueous extracts were studied alone against the growth of the Cryptococcus neoformans H99 reference strain, the fluconazole-tolerant T1-5796 and 89–610 strains, three histone deacetylase (HDAC) genes mutant strains, C. gattii NIH198, Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis to determine minimum inhibitory concentration (MIC). Next, the extracts were employed in combination with aluminium-phthalocyanine chloride nanoemulsion-mediated photodynamic therapy to evaluate a possible interaction. We demonstrated that the C. neoformans T1-5796 fluconazole-tolerant strain was more severely inhibited by the Pp1 isolate extract (MIC: 6 mg mL−1) than H99, which was not inhibited. Growth inhibition of the HDAC null mutants was more prominent for the extract of the UzM isolate, showing inhibition at 2 mg mL−1. The UzM extract was also the most effective in hindering the Candida species proliferation, with MIC values ranging from 10 to 40 mg mL−1. The four Streptomyces extracts, especially UzK and UzM, significantly enhanced the antifungal effect of the photodynamic therapy. Our results indicate these Streptomyces isolates as sources of novel metabolites which could potentiate the effect of photodynamic therapy in controlling yeasts superficial infections. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) effectively kills cancer cells and initiates immune responses that promote anticancer effects locally and systemically. Primarily developed for local and regional cancers, the potential of PDT for systemic antitumor effects [in situ photo‐vaccination (ISPV)] remains underexplored. This study investigates: (1) the comparative effectiveness of paclitaxel (PTX) prodrug [Pc‐(L‐PTX)2] for PDT and site‐specific PTX effects versus its pseudo‐prodrug [Pc‐(NCL‐PTX)2] for PDT combined with checkpoint inhibitors; (2) mechanisms driving systemic antitumor effects; and (3) the prophylactic impact on preventing cancer recurrence. A bilateral tumor model was established in BALB/c mice through subcutaneous injection of CT26 cells. Mice received the PTX prodrug (0.5 μmole kg−1, i.v.), and tumors were treated with a 690‐nm laser (75 mW cm−2 for 30 min, drug‐light interval 0.5 h, light does 135 J cm−1), followed by anti‐CTLA‐4 (100 μg dose−1, i.p.) on days 1, 4, and 7. Notable enhancement in both local and systemic antitumor effectiveness was observed with [Pc‐(L‐PTX)2] compared to [Pc‐(NCL‐PTX)2] with checkpoint inhibitor. Immune cell depletion and immunohistochemistry confirmed neutrophils and CD8+ T cells are effectors for systemic antitumor effects. Treatment‐induced immune memory resisted newly rechallenged CT26, showcasing prophylactic benefits. ISPV with a PTX prodrug and anti‐CTLA‐4 is a promising approach for treating metastatic cancers and preventing recurrence. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment approach. Indocyanine green (ICG) is a water-soluble tricarbocyanine dye with a peak absorption wavelength of around 800 nm and possesses the capacity to produce reactive oxygen species. FTIR spectroscopy is rarely used and offers insights into molecular changes in cancer studies. MCF-7 cells were injected into Nude mouse. Once the tumor had grown to a size of 3–4 mm, mice were randomized into the 12 PDT groups. After each mouse received 5 mg/kg of ICG, they were photo-irradiated with a diode laser emitting light at 809 nm, followed by waiting intervals of 0, 30, 60, and 90 min. Laser irradiation parameters were 150, 250, 500 mW/cm2 and irradiation duration was 1200s. The tumor size was measured every day for four days. The FTIR spectroscopy was used to perform spectral analysis on tumor tissue samples. Four distinct regions (3600–2800 cm-1, 1750–1550 cm-1, 1540–1450 cm-1, and 1700–1100 cm-1) were analyzed, and Hierarchical Cluster study was carried out. A decrease in tumor volume was observed with all PDT applications, except, increases in tumor volume was observed at 150mW 90-minute group. PDT administered after 90 min revealed variations in 150mW and 250mW laser powers in the 3600 cm-1–2800 cm-1 range. The 250mW and 500mW applications resulted in a considerable reduction in fibroadenoma and carcinoma tissues, according to an analysis comparing the A1695 / A1635 ratio. It is proposed that the ideal treatments for further investigation have a power output of 250 mW. [ABSTRACT FROM AUTHOR]

Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18F labeled LABO (18F-LABO) was developed for PET imaging of HCC. LABO and 18F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/18F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC. [ABSTRACT FROM AUTHOR]

Self‐assembled supramolecular DNA tetrahedra composed of programmed sequence‐engineered complementary base‐paired strands represent elusive nanostructures having key contributions to the development and diverse applications of DNA nanotechnology. By appropriate engineering of the strands, DNA tetrahedra of tuneable sizes and chemical functionalities were designed. Programmed functionalities for diverse applications were integrated into tetrahedra structures including sequence‐specific recognition strands (aptamers), catalytic DNAzymes, nanoparticles, proteins, or fluorophore. The article presents a comprehensive review addressing methods to assemble and characterize the DNA tetrahedra nanostructures, and diverse applications of DNA tetrahedra framework are discussed. Topics being addressed include the application of structurally functionalized DNA tetrahedra nanostructure for the assembly of diverse optical or electrochemical sensing platforms and functionalized intracellular sensing and imaging modules. In addition, the triggered reconfiguration of DNA tetrahedra nanostructures and dynamic networks and circuits emulating biological transformations are introduced. Moreover, the functionalization of DNA tetrahedra frameworks with nanoparticles provides building units for the assembly of optical devices and for the programmed crystallization of nanoparticle superlattices. Finally, diverse applications of DNA tetrahedra in the field of nanomedicine are addressed. These include the DNA tetrahedra‐assisted permeation of nanocarriers into cells for imaging, controlled drug release, active chemodynamic/photodynamic treatment of target tissues, and regenerative medicine. [ABSTRACT FROM AUTHOR]

The clinical application of photodynamic therapy (PDT) is limited by oxygen‐dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H‐abstraction reaction can address these challenges because they can generate alkyl radical‐killing cells independently of oxygen and undergo rapid bleaching following H‐abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl‐ketone substituted cyanine (ACy−R), the first red‐light triggered H‐abstraction photoinitiators for hypoxic cancer therapy. These ACy−R molecules inherited the near‐infrared absorption of cyanine dye, and aryl‐ketone modification imparted H‐abstraction capability. Experimental and quantum calculations revealed that modifying the electron‐withdrawing groups of the aryl (e.g. ACy‐5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H‐abstraction ability. Particularly, ACy‐5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy‐5F initiated red‐light induced H‐abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy‐5F was degraded after H‐abstraction, thus avoiding the side effects of long‐term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators. [ABSTRACT FROM AUTHOR]

A first example of a mitochondrial G‐quadruplex (mitoG4s) targeted Ru(II) photooxidant complex is reported. The complex, Ru‐TAP‐PDC3 induces photodamage toward guanine quadruplexes (G4s) located in the mitochondrial genome under hypoxic and normoxic conditions. Ru‐TAP‐PDC3 shows high affinity for mitoG4s and localises within mitochondria of live HeLa cells. Immunolabelling with anti‐G4 antibody, BG4, confirms Ru‐TAP‐PDC3 associates with G4s within the mitochondria of fixed cells. The complex induces depletion of mtDNA in live cells under irradiation at 405 nm, confirmed by loss of PicoGreen signal from mitochondria. Biochemical studies confirm this process induces apoptosis. The complex shows low dark toxicity and an impressive phototoxicity index (PI) of >89 was determined in Hela under very low intensity irradiation, 5 J/cm2. The phototoxicity is thought to operate through both Type II singlet oxygen and Type III pathways depending on normoxic or hypoxic conditions, from live cell assays and plasmid DNA cleavage. Overall, we demonstrate targeting mitoG4s and mtDNA with a photooxidant is a potent route to achieving apoptosis under hypoxic conditions that can be extended to phototherapy. [ABSTRACT FROM AUTHOR]

Self‐assembled supramolecular DNA tetrahedra composed of programmed sequence‐engineered complementary base‐paired strands represent elusive nanostructures having key contributions to the development and diverse applications of DNA nanotechnology. By appropriate engineering of the strands, DNA tetrahedra of tuneable sizes and chemical functionalities were designed. Programmed functionalities for diverse applications were integrated into tetrahedra structures including sequence‐specific recognition strands (aptamers), catalytic DNAzymes, nanoparticles, proteins, or fluorophore. The article presents a comprehensive review addressing methods to assemble and characterize the DNA tetrahedra nanostructures, and diverse applications of DNA tetrahedra framework are discussed. Topics being addressed include the application of structurally functionalized DNA tetrahedra nanostructure for the assembly of diverse optical or electrochemical sensing platforms and functionalized intracellular sensing and imaging modules. In addition, the triggered reconfiguration of DNA tetrahedra nanostructures and dynamic networks and circuits emulating biological transformations are introduced. Moreover, the functionalization of DNA tetrahedra frameworks with nanoparticles provides building units for the assembly of optical devices and for the programmed crystallization of nanoparticle superlattices. Finally, diverse applications of DNA tetrahedra in the field of nanomedicine are addressed. These include the DNA tetrahedra‐assisted permeation of nanocarriers into cells for imaging, controlled drug release, active chemodynamic/photodynamic treatment of target tissues, and regenerative medicine. [ABSTRACT FROM AUTHOR]

The clinical application of photodynamic therapy (PDT) is limited by oxygen‐dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H‐abstraction reaction can address these challenges because they can generate alkyl radical‐killing cells independently of oxygen and undergo rapid bleaching following H‐abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl‐ketone substituted cyanine (ACy−R), the first red‐light triggered H‐abstraction photoinitiators for hypoxic cancer therapy. These ACy−R molecules inherited the near‐infrared absorption of cyanine dye, and aryl‐ketone modification imparted H‐abstraction capability. Experimental and quantum calculations revealed that modifying the electron‐withdrawing groups of the aryl (e.g. ACy‐5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H‐abstraction ability. Particularly, ACy‐5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy‐5F initiated red‐light induced H‐abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy‐5F was degraded after H‐abstraction, thus avoiding the side effects of long‐term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators. [ABSTRACT FROM AUTHOR]

A first example of a mitochondrial G‐quadruplex (mitoG4s) targeted Ru(II) photooxidant complex is reported. The complex, Ru‐TAP‐PDC3 induces photodamage toward guanine quadruplexes (G4s) located in the mitochondrial genome under hypoxic and normoxic conditions. Ru‐TAP‐PDC3 shows high affinity for mitoG4s and localises within mitochondria of live HeLa cells. Immunolabelling with anti‐G4 antibody, BG4, confirms Ru‐TAP‐PDC3 associates with G4s within the mitochondria of fixed cells. The complex induces depletion of mtDNA in live cells under irradiation at 405 nm, confirmed by loss of PicoGreen signal from mitochondria. Biochemical studies confirm this process induces apoptosis. The complex shows low dark toxicity and an impressive phototoxicity index (PI) of >89 was determined in Hela under very low intensity irradiation, 5 J/cm2. The phototoxicity is thought to operate through both Type II singlet oxygen and Type III pathways depending on normoxic or hypoxic conditions, from live cell assays and plasmid DNA cleavage. Overall, we demonstrate targeting mitoG4s and mtDNA with a photooxidant is a potent route to achieving apoptosis under hypoxic conditions that can be extended to phototherapy. [ABSTRACT FROM AUTHOR]

Hydrogel dressings play an important role in the treatment of bacterial infection. In this study, carboxymethyl chitosan (CM‐CS) was cross‐linked with aldehyde polyglycol (DF‐PEG), and then polydopamine (pDA) and 5,10,15, 20‐tetrakis (4‐aminophenyl) porphyrin (TAPP) were grafted to prepare a CM‐CS/DF‐PEG/pDA/TAPP hydrogel (CDPT). The results showed that the CDPT hydrogel had good adhesion, injectability, self‐healing, degradability, and biocompatibility. Under near‐infrared irradiation, the CDPT hydrogel has excellent photothermal and photodynamic effects and can effectively inhibit activity of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and antibiotic‐resistant, methicillin‐resistant Staphylococcus aureus (MRSA). In summary, CDPT hydrogel has potential applications as antibacterial material. [ABSTRACT FROM AUTHOR]

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT's antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection. [ABSTRACT FROM AUTHOR]

Herein, the computer-guided design, chemical synthesis, and biological evaluation of a Ru C polypyridine complex, that could eradicate cancerous cells upon excitation with red light at 630 nm, is reported. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a clinically approved therapeutic modality for treating oncological and non-oncological disorders. PDT has proclaimed multiple benefits over further traditional cancer therapies including its minimal systemic toxicity and selective ability to eliminate irradiated tumors. In PDT, a photosensitizing substance localizes in tumor tissues and becomes active when exposed to a particular wavelength of laser light. This produces reactive oxygen species (ROS), which induce neoplastic cells to die and lead to the regression of tumors. The contributions of ROS to PDT-induced tumor destruction are described by three basic processes including direct or indirect cell death, vascular destruction, and immunogenic cell death. However, the efficiency of PDT is significantly limited by the inherent nature and tumor microenvironment. Combining immunotherapy with PDT has recently been shown to improve tumor immunogenicity while decreasing immunoregulatory repression, thereby gently modifying the anticancer immune response with long-term immunological memory effects. This review highlights the fundamental ideas, essential elements, and mechanisms of PDT as well as nanomaterial-based PDT to boost tumor immunogenicity. Moreover, the synergistic use of immunotherapy in combination with PDT to enhance immune responses against tumors is emphasized. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) and photodynamic therapy (PDT) are potential cancer treatment methods that are minimally invasive with high specificity for malignant cells. Emerging research has concentrated on the application of metal nanoparticles encapsulated in porphyrin and their derivatives to improve the efficacy of these treatments. Gold and silver nanoparticles have distinct optical properties and biocompatibility, which makes them efficient materials for PDT and PTT. Conjugation of these nanoparticles with porphyrin derivatives increases their light absorption and singlet oxygen generation that create a synergistic effect that increases phototoxicity against cancer cells. Porphyrin encapsulation with gold or silver nanoparticles improves their solubility, stability, and targeted tumor delivery. This paper provides comprehensive review on the design, functionalization, and uses of plasmonic silver and gold nanoparticles in biomedicine and how they can be conjugated with porphyrins for synergistic therapeutic effects. Furthermore, it investigates this dual-modal therapy's potential advantages and disadvantages and offers perspectives for future prospects. The possibility of developing gold, silver, and porphyrin nanotechnology-enabled biomedicine for combination therapy is also examined. [ABSTRACT FROM AUTHOR]

Objective: The green synthesis of Tin(IV) oxide (SnO2): Gold (Au) nanoparticles (NPs) using Teucrium polium medicinal plant extract was investigated, and the NPs were characterized and tested as photosensitizers to produce reactive oxygen species (ROS). Methods: The cytotoxic effect on C26 cells was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) technique. The results showed their toxicity in a dose-dependent manner. The green synthesis of SnO2:Au NPs was achieved for the first time using an extract of T. polium medicinal plant as a reducing and stabilizing agent. The produced NPs were examined for their application in photodynamic therapy (PDT) for cancer. Results: Methylene blue and anthracene were used to confirm that the photosensitizer could produce ROS when excited with UVA radiation. The anticancer activity of SnO2:Au was investigated in vitro using the C26 cell line and an MTT assay, showing that PDT with SnO2:Au NPs could inhibit cancer cell proliferation. Conclusions: The significant afterglow of the SnO2:Au NPs could cause the generation of ROS to continue several minutes after switching off the light source. [ABSTRACT FROM AUTHOR]

Aim: To prepare experimental adhesive (EA) with 1% and without chitosan nanoparticles on dentin conditioned with a conventional technique phosphoric acid (PA) compared with two different contemporary techniques: photodynamic therapy (PDT) and femtosecond laser (FSL). Method: The methodology consisted of synthesis of EA and 1% chitosan-modified adhesive (CMA). Scanning electron microscopy, dentin adhesive interface assessment, energy-dispersive spectroscopy, shear bond strength (SBS), degree of conversion (DC), and bond failure were assessed. Teeth were selected, disinfected, and mounted in acrylic up to the cementoenamel junction. Occlusal enamel was removed and teeth were randomly allocated into groups and conditioned. These included Group 1: samples treated with PA; Group 2: specimens conditioned with methylene blue photosensitizer (MBP) activated by PDT; and Group 3: samples conditioned with FSL. Following different conditioning regimes, specimens were bonded using 1% CMA and EA. The composite buildup was followed by SBS testing and a bond failure assessment. DC was assessed for both EA and CMA. Analysis of variance and Tukey's post hoc test were used to compare the mean and standard deviation of SBS and DC in different experimental groups, with a significance level of p < 0.05. d Results: Dentin pretreated with etch and rinse demonstrated the highest bond strength with 1% CMA. Dentin conditioned with MBP activated by PDT and bonded to EA showed the lowest bond scores. Overall SBS values of 1% CMA were better than EA irrespective of the conditioning regime of dentin. The DC was higher in EA adhesive. This was followed by DC in 1% CMA. DC in EA was found to be comparable with 1% CMA. Conclusions: PA remains the gold standard for dentin conditioning. The incorporation of 1% chitosan in adhesive improves SBS and results in no change in DC. The use of FSL in dentin conditioning can be used as an alternative approach as it results in SBS within acceptable limits. The study was approved by the ethical board of King Saud University. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a therapeutic modality that depends on the interaction of light, photosensitizers, and oxygen. The photon absorption and energy transfer process can lead to the Type II photochemical reaction of the photosensitizer and the production of singlet oxygen (1O2), which strongly oxidizes and reacts with biomolecules, ultimately causing oxidative damage to the target cells. Therefore, 1O2 is regarded as the key photocytotoxic species accountable for the initial photodynamic reactions for Type II photosensitizers. This article will provide a comprehensive review of 1O2 properties, 1O2 production, and 1O2 detection in the PDT process. The available 1O2 data of regulatory-approved photosensitizing drugs will also be discussed. [ABSTRACT FROM AUTHOR]

This study evaluates the efficacy and safety of radiofrequency ablation (RFA) in treating low-grade squamous intraepithelial lesions (LSIL) with high-risk human papillomavirus (hrHPV) infection. The clinical data of 100 patients with LSIL and hrHPV infection were retrospectively analyzed. Patients were divided into the RFA group and the 5- aminolevulinic acid photodynamic therapy (ALA-PDT) group according to the treatment protocol, with 50 patients per group. Efficacy, negative hrHPV seroconversion, mental status, treatment satisfaction, and the occurrence of adverse reactions were compared between the two groups. The RFA group had a significantly higher total effective rate (94.00%) than the ALA-PDT group (74.00%). At 3 and 6-month follow-ups, the negative hrHPV seroconversion rate was significantly higher in the RFA group than in the ALA-PDT group (p < 0.05). At 6 months after treatment, the RFA group showed significantly lower Self-Rating Anxiety Scale scores and Self-Rated Depression Scale scores and higher satisfaction compared to the ALA-PDT group (all p < 0.05). The incidence of postoperative complications rate was not significantly different between the RFA group and ALA-PDT group (χ² = 3.184, p = 0.074). RFA is an effective and safe treatment that improves anxiety, depression, and satisfaction in patients with LSIL complicated by hrHPV infection. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. Objectives We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011–2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting. Methods The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors. Results The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT. Conclusions ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT. [ABSTRACT FROM AUTHOR]

Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG. 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up. The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy. [ABSTRACT FROM AUTHOR]

A nanoemulsion containing CdTe quantum dots (NE-CdTe-QD) was developed to shield cells from cadmium toxicity and shown to be a promising candidate for brain tumor diagnosis. CdTe-QD was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. CdTe-QD exhibited high luminescence emission at 700 nm, and their stability was maintained when encapsulated in lipidic/polymeric nanoemulsions (198 ± 2.0 nm; PDI = 0.174; − 49.0 mV). The biological effects of free and nanoemulsified CdTe-QD were tested in normal cells (NHF) and glioblastoma cell lines (U87-MG and T98G). Membrane colocalization of NE-CdTe-QD by T98G cells was observed. Instead, intracellular endoplasmic reticulum localization of NE-CdTe-QD was verified in U87-MG cells. Cell viability was reduced only when NE-CdTe-QD permeated the membrane of GBM cells, as observed in U87-MG cells, whereas no cytotoxic effects were observed in normal fibroblasts. Incorporating quantum dots directly into the brain cells is difficult. However, the nanoemulsions reduced the toxicity of CdTe-QD in zebrafish larvae and increased their circulation time, and direct injection into the zebrafish brain did not affect neural cell viability. This validates the potential application of these nanomaterials as diagnostic agents and satisfies the necessary criteria for their use as photosensitizers in photodynamic therapy. [ABSTRACT FROM AUTHOR]