Photodynamic Damage Research Articles

Antibacterial effect of semiconductor laser radiation against the strains of S. aureus and P. aeruginosa, leading pathogens in osteomyelitis

Introduction The study of the antibacterial effect of photodynamic therapy against the leading pathogens of chronic osteomyelitis is one of the promising directions today.Purpose of the work was to evaluate the antibacterial effect against the strains of Staphylococcus aureus and Pseudomonas aeruginosa with the ALOD-01 laser system in the presence of photodithazine.Materials and methods The object of the study was 24-hour archival cultures of gram-positive and gram-negative microorganisms belonging to two taxa: Staphylococcus aureus (25923), Pseudomonas aeruginosa (27853). The antibacterial effect after the exposure to laser radiation in the presence of photodithazine on the microbial cells of the studied cultures was assessed by the absence of microorganism growth in the area of the light beam.Results Laser exposure in combination with photodithazine (concentration 0.5–1.0 mg/ml) on S. aureus for two minutes at 200–300 J achieved a bactericidal effect in the beam area. A bactericidal effect on the entire surface of the Petri dish was achieved with light exposure of 400 J for 5 minutes and a photodithazine concentration of 1.0 mg/ml. Laser exposure for 2 minutes in the presence of photodithazine at a concentration of 0.5 mg/ml and 1 mg/ml did not have an antibacterial effect on P. aeruginosa strains. Continuous growth of microorganisms was observed on the dish. Increasing the light dose and exposure time contributed to a decrease in the growth of microbial cells. A bactericidal effect was obtained only in the center of the dish in treating the bacterial suspension with photodithazine at a concentration of 5 mg/ml.Discussion The effectiveness of PDT depends on the type of microorganisms, the anatomical location of the infection site, as well as the properties of the photosensitizer and the laser used. Depending on the structure of the cell wall, different susceptibility of bacteria to photodynamic effects is observed.Conclusion S. aureus strains can be successfully photoinactivated using photodithazine. For P. aeruginosa strains, it was not possible to find a regime in which microbial cell growth was absent throughout the dish. The photodynamic reaction occurs only when adequate doses of light energy act on the photosentisizer in the presence of oxygen in the medium, while the photodynamic damage is local and the bactericidal effect is limited by the zone of light exposure.

Synergistic Enhancement of Photodynamic Cancer Therapy with Mesenchymal Stem Cells and Theranostic Nanoparticles.

Nanoparticles engineered to combat cancer and other life-threatening diseases may significantly improve patient outcomes. However, inefficient nanoparticle delivery to tumors limits their use and necessitates the development of complex delivery approaches. Here, we examine this issue by harnessing the tumor-homing abilities of human mesenchymal stem cells (MSCs) to deliver a decoupled theranostic complex of rare earth-doped nanoparticles (dNPs) and photosensitizer chlorin e6 (Ce6) to tumors. We show that both bone-marrow- and skin-derived MSCs can transport the dNP-Ce6 complex inside tumor spheroids, which is challenging to accomplish by passive delivery alone. MSCs deliver the dNP-Ce6 complex across the tumor spheroid, facilitating more effective photodynamic damage and tumor destruction than passively accumulated dNP-Ce6. The dNP-Ce6 complex also provides the built-in ability to monitor the MSC migration without causing undesired phototoxicity, which is essential for maximal and side-effect-free delivery of nanoparticles. Our results demonstrate how MSCs can be used as delivery vehicles for the transportation of the dNP-Ce6 complex, addressing the limitations of passive nanoparticle delivery and providing light-based theranostics.

Generation of singlet oxygen inside living cells: correlation between phosphorescence decay lifetime, localization and outcome of photodynamic action

Photodynamic therapy (PDT) is a promising alternative treatment for localized lesions and infections, utilizing reactive oxygen species (ROS) generated by photosensitizers (PS) upon light activation. Singlet oxygen (1O2) is a key ROS responsible for photodynamic damage. However, the effectiveness of PS in biological systems may not correlate with the efficiency of singlet oxygen generation in homogeneous solutions. This study investigated singlet oxygen generation and its decay in various cellular microenvironments using liposome and ARPE-19 cell models. Rose Bengal (RB), methylene blue (MB), and protoporphyrin IX (PpIX) were employed as selected PS. Lifetimes of singlet oxygen generated by the selected photosensitizers in different cellular compartments varied, indicating different quenching rates with singlet oxygen. RB, located near cell membranes, exhibited the highest phototoxicity and lipid/protein peroxidation, followed by PpIX, while MB showed minimal cytotoxicity in similar conditions. Singlet oxygen decay lifetimes provide insights into PS localization and potential phototoxicity, highlighting the importance of the lipid microenvironment in PDT efficacy, providing useful screening method prior to in vivo applications.Graphical abstract

Reduction of photodynamic damage of blood vessels in the protected region by (–)-epigallocatechin gallate

Photodynamic therapy (PDT) has been increasingly used in the clinical treatment of neoplastic, inflammatory and infectious skin diseases. However, the generation of reactive oxygen species (ROS) may induce undesired side effects in normal tissue surrounding the treatment lesion, which is a big challenge for the clinical application of PDT. To date, (–)-Epigallocatechin gallate (EGCG) has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage. This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether (Hemoporfin)-mediated PDT. The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be [Formula: see text] M−1S−1 and [Formula: see text] M−1S−1, respectively. The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel, suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG. This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2, and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

Dual plastid targeting of protoporphyrinogen oxidase 2 in Amaranthaceae promotes herbicide tolerance.

Plant tetrapyrrole biosynthesis (TPB) takes place in plastids and provides the chlorophyll and heme required for photosynthesis and many redox processes throughout plant development. TPB is strictly regulated, since accumulation of several intermediates causes photodynamic damage and cell death. Protoporphyrinogen oxidase (PPO) catalyzes the last common step before TPB diverges into chlorophyll and heme branches. Land plants possess two PPO isoforms. PPO1 is encoded as a precursor protein with a transit peptide, but in most dicotyledonous plants PPO2 does not possess a cleavable N-terminal extension. Arabidopsis (Arabidopsis thaliana) PPO1 and PPO2 localize in chloroplast thylakoids and envelope membranes, respectively. Interestingly, PPO2 proteins in Amaranthaceae contain an N-terminal extension that mediates their import into chloroplasts. Here, we present multiple lines of evidence for dual targeting of PPO2 to thylakoid and envelope membranes in this clade and demonstrate that PPO2 is not found in mitochondria. Transcript analyses revealed that dual targeting in chloroplasts involves the use of two transcription start sites and initiation of translation at different AUG codons. Among eudicots, the parallel accumulation of PPO1 and PPO2 in thylakoid membranes is specific for the Amaranthaceae and underlies PPO2-based herbicide resistance in Amaranthus species.

Photodynamic therapy of acne

Acne is one of the most common skin conditions in the world. A number of studies have shown that photodynamic therapy (PDT) is safe and effective for both inflammatory and non-inflammatory acne and can significantly improve skin conditions in this disease. The effectiveness of PDT against acne is mainly due to a decrease in the amount of sebum produced by the sebaceous glands due to a decrease in their activity as a result of direct photodynamic damage to the sebaceous glands, eradication of Cutibacterium acnes, and a decrease in the level of hyperkeratosis. Compared with systemic drug therapy, PDT treatment of severe acne has the following advantages: fast results, high efficiency, high selectivity, no systemic adverse reactions and drug resistance, and low recurrence rate. Most often for PDT in patients with acne, drugs based on 5-aminolevulinic acid (5-ALA) and its methyl ester (ME-ALA) are used. At the moment, there are no unified recommendations on PDT regimens for the treatment of this skin pathology. Various studies demonstrate the high efficiency of PDT with a wide range of doses of 5-ALA (3-20%) and ME-ALA (4-16%), light doses (15-120 J/cm2 ), and exposure time (30-90 min). The general trend in studies by different authors is that gentle low-intensity PDT regimens for acne demonstrate the same high efficiency with a significant reduction in pain during irradiation and local skin reactions (erythrema, edema, and hyperpigmentation).

A laser free self-luminous nanosystem for photodynamic therapy of cervical cancer cells

Photodynamic therapy is a tumor treatment strategy. However, most of the photodynamic therapies rely on laser irradiation triggering, which limits their application in deep tissues. This study designed a self-luminescent nano system, hybrid protein oxygen nanocarrier coated graphene quantum dots (GQDs@HPOC) and mesoporous silica nanoparticles coated Luminol (L@MSNs), which self-assembled into GQDs@HPOC/L@MSNs without laser irradiation. The system utilized the weak acidic environment of tumors to trigger the release of Luminol and the chemiluminescence was catalyzed by HPOC. Next CRET occurred between Luminol and GQDs, producing 1O2, which could generate photodynamic damage to cervical cancer cells without the need for external laser irradiation. The system achieved the peak uptake in primary cervical cancer cells in 3 h, and had good biosafety before self-assembly. The system could significantly kill cells at a concentration of 16 μg/ml. The system will be further applied in in vivo experiments to investigate its therapeutic ability, providing a new strategy for the clinical treatment of cervical cancer.

The potential effect of leptin co-administration on photodynamic damage using quail chorioallantoic membrane model

BackgroundThe chorioallantoic membrane (CAM) of the Japanese quail is an excellent model for studying photodynamic therapy (PDT) due to its rich vascularization. PDT is used not only in oncological treatment but also in infectious diseases, or psoriasis, where it yields significant advantages. This treatment also has its limitations, such as burning, itching, erythema, redness, swelling, and delayed wound healing. The aim of this study was to analyse the potentially protective properties of the tissue hormone leptin during PDT. MethodsJapanese quail embryos incubated ex ovo were used in this experiment. On the 9th day of embryonic development, leptin (5 μg) and photosensitiser hypericin (79 μM) were topically applied, followed by irradiation. The effect of leptin co-administration was evaluated from CAM images and histological structure analysis, histological samples, and qPCR, where the expression of genes involved in angiogenesis, apoptosis, and oxidative stress was monitored. ResultsWe observed vascular damage in all experimental groups, the highest damage was found after the application of hypericin without leptin coadministration. Histological analysis confirmed the protective effect of leptin. qPCR analysis presented differences in FREK gene expression, but also in genes involved in oxidative stress like SOD, NRF-1, NRF-2, and GPX7. The application of leptin significantly reduced the expression of apoptosis regulatory proteins CASP3, cytochrome C, and APAF1. ConclusionsOur results in the CAM model suggest a possible protective effect of leptin to prevent PDT damage and aid in the subsequent regeneration of target tissues after antimicrobial PDT.

Flexible Modulation of Cellular Activities with Cationic Photosensitizers: Insights of Alkyl Chain Length on Reactive Oxygen Species Antimicrobial Mechanisms.

Cationic photosensitizers have good binding ability with negatively charged bacteria and fungi, exhibiting broad applications potential in antimicrobial photodynamic therapy (aPDT). However, cationic photosensitizers often display unsatisfactory transkingdom selectivity between mammalian cells and pathogens, especially for eukaryotic fungi. It is unclear which biomolecular sites are more efficient for photodynamic damage, owing to the lack of systematic research with the same photosensitizer system. Herein, a series of cationic aggregation-induced emission (AIE) derivatives (CABs) (using berberine (BBR) as the photosensitizers core) with different length alkyl chains are successfully designed and synthesized for flexible modulation of cellular activities. The BBR core can efficiently produce reactive oxygen species (ROS) and achieve high-performance aPDT . Through the precise regulation of alkyl chain length, different bindings, localizations, and photodynamic killing effects of CABs are achieved and investigated systematically among bacteria, fungi, and mammalian cells. It is found that intracellular active substances, not membranes, are more efficient damage sites of aPDT. Moderate length alkyl chains enable CABs to effectively kill Gram-negative bacteria and fungi with light, while still maintaining excellent mammalian cell and blood compatibility. This study is expected to provide systematic theoretical and strategic research guidance for the construction of high-performance cationic photosensitizers with good transkingdom selectivity.

Homotypic Targeted Photosensitive Nanointerferer for Tumor Cell Cycle Arrest to Boost Tumor Photoimmunotherapy.

Recent advances in tumor immunotherapy mainly tend to remodel the immunosuppressive tumor microenvironment (TME) for immune enhancement. However, the complexity of TME makes it unlikely to achieve satisfactory therapeutic effects with any single intervention alone. Here, we focus on exposing intrinsic features of tumor cells to trigger direct pleiotropic antitumor immunity. We develop a photosensitive nanointerferer that is engineered with a nanoscale metal-organic framework decorated with tumor cell membranes for targeted delivery of a photosensitizer and small interfering RNA, which is used to knock down cyclin-dependent kinase 4 (Cdk4). Cdk4 blockade can arrest the cell cycle of tumor cells to facilitate antigen exposure and increase the expression level of programmed cell death protein ligand 1 (PD-L1). Under laser irradiation, photodynamic damage triggered by the nanointerferer induces the release of tumor antigens and recruitment of dendritic cells (DCs), thereby promoting the antitumor activity of CD8+ T cells in combination with anti-PD-L1 antibodies. Ultimately, these events markedly retard tumor progression in a mouse model of ectopic colon tumor with negligible adverse effects. This study provides an alternative treatment for effective antitumor immunity by exciting the intrinsic potential of tumor cells to initiate immune responses while reducing immune-related toxicities.

Antioxidant effect evaluation of drugs with different chemical structures by the degree of mast cell degranulation under photodynamic damage

Introduction. This model of skin acute inflammation caused by photodynamic damage (PHD), where reactive oxygen species (ROS) play a key role, enables the analysis of the microcirculation (MCC) dysfunction and degranulation of mast cells (MCs) at the site of exposure. The current study explored the IgE-independent mechanisms of MCs activation caused by PHD and the possibility of its pharmacological correction. Aim of the study – to evaluate the possibilities of using the model of acute inflammation induced by ROS during PHD to study the MCs contribution to the regulation of vascular permeability and to study angioprotective and MCC-improving drugs at the preclinical stage. Materials and methods. Male Wistar rats were injected with a photosensitizer, then anesthetized and laser irradiated 3 hours later, followed by one of the following drugs: hydrocortisone (HC), ethylmethylhydroxypyridine succinate (ES), or quinacrine (QC). Skin MCC was investigated by laser Doppler flowmetry. Calculation and morphometry of MCs was carried out on film preparations of loose connective tissue of the skin. Results. Immediately after PHD, the blood flow in the control group was 1.9 [1.4; 2.3] p. u., which is 55 % less than the initial values. Partial restoration of blood flow up to 3.7 [3.3; 4.0] p.u. was observed after one hour of observation (88 % of baseline, p<0.001). Despite the administration of HC and ES, the blood flow after PHD decreased by 8,5 and 32,5 %, respectively. After an hour, it was only 78 % of the baseline. Intravenous administration of QC immediately after irradiation, lead to decrease of the blood flow only 28 %, and after an hour the blood flow was completely restored. The degree of MCs degranulation after the intravenous administration of HC and QC is almost equal and characterized by a decrease in the number of MCs with complete (anaphylactic) degranulation to 27.5 [21.6; 29.4] and 26.4 [22.5; 32.5] %, respectively, versus 46.9 [47.7; 52] % in the control group (p<0,05); however, after the administration of ES, the results are comparable with the intact control. Non-parametric correlation analysis did not reveale statistically significant difference between blood flow one hour after photodynamic exposure and morphometric types of MCs in groups with various drugs. Conclusion. Differences between the drug effects on the skin blood flow and the IgE-independent MCs activation is confirmed by the absence of a correlation between these parameters. QC, in comparison with ES and HC, is more effective in relation to dysfunction of the skin MCC. Under these conditions, the combined use of anti-inflammatory and antioxidant drugs seems promising.

Structural alterations in cell organelles induced by photodynamic treatment with chlorin p6 -histamine conjugate in human oral carcinoma cells probed by 3D fluorescence microscopy.

We have explored the intracellular cell organelle's structural alterations after photodynamic treatment with chlorin p6 -histamine conjugate (Cp6 -his) in human oral cancer cells. Herein, the cells were treated with Cp6 -his (10μm) and counterstained with organelle-specific fluorescence probes to find the site of intracellular localization using confocal microscopy. For photodynamic therapy (PDT), the cells were exposed to ~30 kJ/m2 red light (660 ± 20 nm) to induce ~90% cytotoxicity. We used the three-dimensional (3D) image reconstruction approach to analyze the photodynamic damage to cell organelles. The result showed that Cp6 -his localized mainly in the endoplasmic reticulum (ER) and lysosomes but not in mitochondria and Golgi apparatus (GA). The 3D model revealed that in necrotic cells, PDT led to extensive fragmentation of ER and fragmentation and swelling of GA as well. Results suggest that the indirect damage to GA occurred due to loss of connection between ER and GA. Moreover, in damaged cells with no sign of necrosis, the perinuclear ER appeared condensed and surrounded by several small clumps at the peripheral region of the cell, and the GA was observed to form a single condensed structure. Since these structural changes were associated with apoptotic cell death, it is suggested that the necrotic and apoptotic death induced by PDT with Cp6 -his is determined by the severity of damage to ER and indirect damage to GA. The results suggest that the indirect damage to cell organelle apart from the sites of photosensitizer localization and the severity of damage at the organelle level contribute significantly to the mode of cell death in PDT.

Photodynamic control of citrus crop diseases.

Citrus are economically important fruit crops to which infectious diseases like citrus canker caused by Xanthomonas citri subs. citri, citrus variegated chlorosis caused by Xylella fastidiosa, "huanglongbing" associated with the presence of Candidatus liberibacter species, anthracnose caused by Colletotrichum gloeosporioides and citrus black spot caused by Phyllosticta citricarpa, impose significant losses. Control measures involve chemical treatment of orchards but often, eradication of infected plants is unavoidable. To circumvent the environmental impacts of pesticides and the socio-economic impacts of eradication, innovative antimicrobial approaches like photodynamic inactivation are being tested. There is evidence of the susceptibility of Xanthomonas citri subs. citri and C. gloeosporioides to photodynamic damage. However, the realistic assessment of perspectives for widespread application of photodynamic inactivation in the control of citrus diseases, necessarily implies that other microorganisms are also considered. This review intends to provide a critical summary of the current state of research on photodynamic inactivation of citrus pathogens and to identify some of the current limitations to the widespread use of photodynamic treatments in citrus crops.

Modulating photochemical reactions in Langmuir monolayers of Escherichia coli lipid extract with the binding mechanisms of eosin decyl ester and toluidine blue-O photosensitizers

Photodynamic damage to the cell envelope can inactivate microorganisms and may be applied to combat super-resistance phenomenon, empowered by the indiscriminate use of antibiotics. Efficiency in microbial inactivation is dependent on the incorporation of photosensitizers (PS) into the bacterial membranes to trigger oxidation reactions under illumination. Herein, Langmuir monolayers of Escherichia coli lipid extract were built to determine the binding mechanisms and oxidation outcomes induced by eosin decyl ester (EosDEC) and toluidine blue-O (TBO) PSs. Surface-pressure isotherms of the E. coli monolayers were expanded upon EosDEC and TBO, suggesting incorporation of both PSs. Fourier-transform infrared spectroscopy (FTIR) of Langmuir-Schaefer (LS) films reveled that the EosDEC and TBO binding mechanisms are dominated by electrostatic interactions with the anionic polar groups, with limited penetration into the chains. Light-irradiation reduced the relative area of E. coli monolayer on TBO, indicating an increased loss of material to the subphase owing to the chain cleavage, generated by contact-dependent reactions with excited states of TBO. In contrast, the increased relative area of E. coli monolayers containing EosDEC suggests lipid hydroperoxidation, which is PS contact-independent. Even considering a small chain penetration, the saturated EosDEC may have partitioned towards saturated reach domains, avoiding direct contact with membrane unsaturations.

Efficient Anticancer Effect on Choroidal Melanoma Cells Induced by Tanshinone IIA Photosensitization

Tanshinone IIA (TanIIA) has multiple biological functions and already been clinically used to treat many cardiovascular diseases. TanIIA is a photoactive molecule and can be excited by light to generate 3 TanIIA*. Generation of 3 TanIIA* by TanIIA photosensitization indicates that TanIIA may serve as a photosensitizer to bring photodynamic damage to organisms. Therefore, human choroidal melanoma MUM-2B cell was chosen as a superficial tumor model and the photodynamic effect of TanIIA on tumor cells was evaluated in this study. The results showed that TanIIA photosensitization could generate singlet oxygen in noncellular system. MTT, clone formation and wound-healing assays showed that the survival and migration of MUM-2B cells could be efficiently inhibited by TanIIA photosensitization. And then, laser confocal microscope and flow cytometry were used to try to elucidate related mechanism. It was found that TanIIA could pass through cellular membrane and preferably accumulate in nucleus. TanIIA photosensitization could efficiently induce cell apoptosis and necrosis, increase intracellular ROS levels, decrease mitochondria membrane potential, and lead to cell cycle arrest in G2/M phase. Our findings indicate that TanIIA photosensitization can exert remarkable toxicity on choroidal melanoma cells.

Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders.

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.

Interaction of Cp6-his and Cp6 with bovine serum albumin and liver microsomes: Spectroscopic and molecular docking studies

The conjugation of photosensitizer with a molecule specific to receptors over-expressed on cancer cells is a promising approach for improving tumor selectivity in photodynamic therapy (PDT). Since chemical nature of the photosensitizer is also affected by conjugation, this can have significant influence on its transport by serum proteins and clearance via liver microsomal enzyme system. In this report, the interaction of chlorin p6-histamine conjugate (Cp6-his) and free chlorin p6 (Cp6) with bovine serum albumin (BSA) and mouse liver microsomes was assessed by measuring the quenching of intrinsic tryptophan (Trp) fluorescence of proteins. The effect of photosensitizer binding on the activity of microsomal NADPH-cytochrome P-450 and NADH-cytochrome b5 reductase was also determined. The formation of protein carbonyl and lipid peroxides was measured to assess the photodynamic damage to proteins and lipids respectively. Further, the binding interaction between Cp6-his conjugate and parent Cp6 with BSA and cytochrome P-450 was validated using in-silico molecular docking approach. Results show that as compared to free Cp6, the affinity of conjugate to bind with serum albumin is 4 orders of magnitude less, which was also corroborated with finding of docking studies. In contrast, with microsomal proteins the binding affinity of Cp6-his was observed to be lower by 2 orders of magnitude as compared to that for Cp6. Further, the inhibition of the activities of microsomal enzymes induced by Cp6 conjugate and free Cp6 was nearly same (~15-20%). Measurements on quenching of photosensitizer fluorescence by iodide ions revealed that conjugate localized slightly deeper in microsomal membrane as compared to free Cp6 consistent with the slight difference in lipophilicity of the two photosensitizers. The amount of photodynamic damage to BSA induced by Cp6-his was significantly less as compared to that for Cp6, whereas no difference was observed in damage induced to microsomal protein and lipid. These results suggest that conjugation of Cp6 to histamine affects its binding to albumin but doses not significantly alters its interaction with microsomal enzyme system.

Encapsulation of Methylene Blue in Zeolitic Imidazolate Framework-90 Nanoparticles to Protect Its Photodynamic Activity.

Methylene blue (MB) is widely used as a photosensitizer in photodynamic therapy applications. However, it is easily reduced by reductases in biological environments, which hampers its further applications. Here, we developed a one-pot method to synthesize MB-encapsulated and poly(vinylpyrrolidone) (PVP)-modified zeolitic imidazolate framework-90 (ZIF-90) nanoparticles (MB@ZIF-90/PVP NPs). The NPs show intact crystalline structure with improved colloidal dispersity and stability both in water and in the medium for cell culture. The size of the enzymes is much larger than the pore size of ZIF-9; thus, the access of reductive enzymes to encapsulated MB is prohibited, resulting in the protection of MB's photodynamic activity. Furthermore, cell experiments confirm that MB@ZIF-90/PVP NPs have lower dark cytotoxity than equivalent free MB but can efficiently induce photodynamic damage to tumor cells even in the presence of reductive enzymes upon light irradiation.

Retraction of "Pathogen-Specific Polymeric Antimicrobials with Significant Membrane Disruption and Enhanced Photodynamic Damage To Inhibit Highly Opportunistic Bacteria".

Retraction of "Pathogen-Specific Polymeric Antimicrobials with Significant Membrane Disruption and Enhanced Photodynamic Damage To Inhibit Highly Opportunistic Bacteria".

Tumor-targeted upconverting nanoplatform constructed by host-guest interaction for near-infrared-light-actuated synergistic photodynamic-/chemotherapy

The strategic combination of photodynamic therapy and chemotherapy has emerged as a promising treatment option for various tumor indications, which not only expands our understanding of each individual modality but also reveals new opportunities to achieve superadditive benefit via exploring their internal synergy rather than simple mixing. In this study, dual-emissive upconverting nanoparticle (UCNP) was employed to bridge the two treatment regimens to synergistically reinforce the therapeutic efficacy. The UCNP-based drug delivery nanoplatform was first co-loaded with 1,8-dihydroxy-3-methylanthraquinone (DHMA) photosensitizers and UV-activatable camptothecin prodrug (NBCCPT) and then complexed with biofunctional β-cyclodextrin species (β-CD-PEG-LA) via highly specific host-guest interactions to cap the camptothecin prodrug conjugated on the nanoparticle surface. The supramolecularly attached β-CD-PEG-LA could not only enhance the aqueous dispersity of the nanocarriers and prevent DHMA leakage, but also imbues targeting effect against asialoglycoprotein receptor-overexpressing tumor cells. The UCNP core would convert the NIR excitation (980 nm) into localized UV (360 nm) and visible (480 nm) emissions, of which the former would cleave the nitrobenzene linker to restore the cytotoxicity of CPT while the latter could excite the photosensitizer to generate reactive oxygen species (ROS). In addition to the photodynamic damage, the light-generated ROS could also facilitate the endo/lysosomal escape of the endocytosed nanoparticles and improve the overall antitumor potency in a synergistic manner.