Fly into the light: eliminating Drosophila melanogaster with chlorophyllin-based Photodynamic Inactivation.

Fruit flies spoil crops in agricultural settings. As conventional pesticides may generate negative off-target effects on humans or the environment, existing treatment methods need eco-friendly and safe alternatives. Photodynamic Inactivation (PDI) is based on the photosensitizer-mediated and light-induced overproduction of reactive oxygen species in targets. We here explore the potential of PDI for the control of fruit fly pests. Drosophila melanogaster serves as well-established model organism in this study. Two distinct experimental approaches are presented: the feed assay, in which fruit flies are provided with sodium magnesium chlorophyllin (Chl, approved as food additive E140) along with sucrose (3%) as their food, and the spray assay, where the photosensitizer is sprayed onto the insects. We show that PDI based on Chl can induce moribundity rates of Drosophila melanogaster of more than 99% with 5 mM Chl and LED illumination (395 nm, 8 h incubation in the dark, radiant exposure 78.9 J/cm2) with the feed assay. If the radiant exposure is doubled to 157.8 J/cm2, 88% of insects are killed by PDI based on 1 mM Chl. The photoactive compound is also effective if presented on strawberries without addition of sucrose with somewhat lower moribundity (71% at 5 mM Chl). Spraying Chl onto insects is less effective than feeding the photosensitizer: 5 mM Chl resulted in 79.5% moribundity (drug to light interval 8 h, radiant exposure 78.9 J/cm2), but if 5 h of sun light (532 J/cm2) and overnight (14 h) dark incubation is used for activation of Chl, more than 95% of insects are killed. As conclusion, Chl serves as effective photoinsecticide against Drosophila melanogaster if a drug to light interval of 8 h is maintained. Feeding the photoactive compound together with sucrose is more effective than spraying it onto insects and increasing the radiant exposure allows for lowering the photosensitizer concentration. Photodynamic Inactivation might therefore represent an eco-friendly addition to the farmers armamentarium against (semi-transparent) insects.

Porphin e6 complex loaded with gold nanorod mesoporous silica enhances photodynamic therapy in ovarian cancer cells in vitro.

A growing amount of experimental evidence has proven that the application of gold nanorods (AuNRs) in photodynamic therapy (PDT) can significantly enhance its therapeutic efficacy. The aim of this study was to establish a protocol for investigating the effect of gold nanorods loaded with the photosensitizer chlorin e6 (Ce6) on photodynamic therapy in the OVCAR3 human ovarian cancer cell line in vitro and to determine whether the PDT effect was different from that of Ce6 alone. OVCAR3 cells were randomly divided into three groups: the control group, Ce6-PDT group, and AuNRs@SiO2@Ce6-PDT group. Cell viability was measured by MTT assay. The generation of reactive oxygen species (ROS) was measured by a fluorescence microplate reader. Cell apoptosis was detected by flow cytometry. The expression of apoptotic proteins was detected by immunofluorescence and western blotting. The results showed that compared with that of the Ce6-PDT group, the cell viability of the AuNRs@SiO2@Ce6-PDT group was significantly decreased (P < 0.05) in a dose-dependent manner, and ROS production increased significantly (P < 0.05). The flow cytometry results showed that the proportion of apoptotic cells in the AuNRs@SiO2@Ce6-PDT group was significantly higher than that in the Ce6-PDT group (P < 0.05). Immunofluorescence and western blot results showed that the protein expression levels of cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in the AuNRs@SiO2@Ce6-PDT-treated-OVCAR3 cells were higher than those in the Ce6-PDT-treated cells (P < 0.05), and the protein expression levels of caspase-3, caspase-9, PARP, and Bcl-2 were slightly lower than those in the Ce6-PDT group (P < 0.05). In summary, our results show that AuNRs@SiO2@Ce6-PDT has a significantly stronger effect on OVCAR3 cells than the effect of Ce6-PDT alone. The mechanism may be related to the expression of Bcl-2 family and caspase family in the mitochondrial pathway.

Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment.

Photodynamic therapy (PDT) induces apoptosis of cancer cells by generating cytotoxic reactive oxygen species, the therapeutic effect of which, however, is impeded by intrinsic/inducible apoptosis-resistant mechanisms in cancer cells and hypoxia of tumor microenvironment (TME); also, PDT-induced anti-tumor immunity activation is insufficient. To deal with these obstacles, a novel biomimetic nanoplatform is fabricated for the precise delivery of photosensitizer chlorin e6 (Ce6), hemin and PEP20 (CD47 inhibitory peptide), integrating oxygen-boosted PDT, ferroptosis activation and CD47-SIRPα blockade. Hemin's catalase-mimetic activity alleviates TME hypoxia and enhances PDT. The nanoplatform activates ferroptosis via both classical (down-regulating glutathione peroxidase 4 pathway) and non-classical (inducing Fe2+ overload) modes. Besides the role of hemin in consuming glutathione and up-regulating heme oxygenase-1 expression, interestingly, we observe that Ce6 enhance ferroptosis activation via both classical and non-classical modes. The anti-cancer immunity is reinforced by combining PEP20-mediated CD47-SIRPα blockade and PDT-mediated T cell activation, efficiently suppressing primary tumor growth and metastasis. PEP20 has been revealed for the first time to sensitize ferroptosis by down-regulating system Xc-. This work sheds new light on the mechanisms of PDT-ferroptosis activation interplay and bridges immunotherapy and ferroptosis activation, laying the theoretical foundation for novel combinational modes of cancer treatment.

Multifunctional Carbon-Dot-Photosensitizer Nanoassemblies for Inhibiting Amyloid Aggregates, Suppressing Microbial Infection, and Overcoming the Blood-Brain Barrier.

Amyloid aggregation, microbial infection, and the blood-brain barrier (BBB) are considered critical obstructions for the treatment of Alzheimer's disease (AD). At present, existing treatment strategies are rarely able to overcome these critical factors. Herein, we propose an innovative treatment strategy and design multifunctional nanoassemblies (yCDs-Ce6) from coassembling photosensitizers (chlorine e6) and yellow fluorescent carbon dots, which endow yCDs-Ce6 with the functions for photodynamic and photothermal therapy (PDT and PTT). Compared with reported inhibitors, yCDs-Ce6 can suppress amyloid aggregation for 7 days, disaggregate aggregates, reduce amyloid aggregation-induced cytotoxicity, and prevent microbial growth by PDT and PTT. Moreover, yCDs-Ce6 can specifically target amyloid aggregates and visually label amyloid aggregates. yCDs-Ce6 can also cross the BBB upon near-infrared light irradiation and clear amyloid deposition in APP/PS1 mice by PDT and PTT. Meanwhile, yCDs-Ce6 did not cause significant negative effects on normal cells or tissues. Based on the methods of PPT and PTT treatment, the research deeply explores the effect of the novel nanoassemblies on two hypotheses of AD, opening a novel therapeutic paradigm for research amyloid-related diseases.

Relationship between lifespan and somatic mutation in D. melanogaster after treatment with chlorophyllin.

Sodium copper chlorophyllin (SCC) has a genetic damage inhibitory capacity due to its antioxidant action. For this reason, it was considered to investigate its role in the life span of Drosophila melanogaster and its relationship with the frequency of somatic mutation induced by gamma rays. Results indicated that SCC alone prolonged the lifespan only in females, but in combination with 20 Gy of gamma rays, the aging delay in both sexes was significant. In addition to confirming that the porphyrin reduces the frequency of mutation, the individuals with the highest mutation load are the individuals who die more quickly, and once they are eliminated, the survivor individuals treated with 20 Gy or with SCC + 20 Gy, died at the same rate. The results together indicate that SCC not only inhibits induced genetic damage, but it also has beneficial effects that probably cause an aging delay of the treated population that need to be investigated.

Penetration and photodynamic ablation of drug-resistant biofilm by cationic Iron oxide nanoparticles.

As we step into the post-antibiotic era, the accelerated emergence of antibiotic-resistant pathogenic bacteria poses an increasingly serious threat to public health. The formation of antibiotic-resistant biofilms further challenges currently available drugs and treatment options, calling for novel strategies for effective ablation of such biofilm with minimal concern on safety and development of resistance. Herein, we report a novel type of photodynamic nanoagent, composed of chlorin e6 (Ce6)-loaded water-soluble chitosan-coated iron oxide nanoparticles (named Ce6@WCS-IONP), for drug-resistant bacteria killing and biofilm eradication. The fabricated Ce6@WCS-IONP has negligible toxicity to mammalian cells and exhibited equivalent singlet oxygen generation capacity to free Ce6; however, its association with methicillin-resistant Staphylococcus aureus (MRSA) was greatly enhanced, as evidenced by flow cytometry analysis and transmission electron microscope. In vitro studies verified that Ce6@WCS-IONP has superior photodynamic bactericidal effect against planktonic MRSA. Furthermore, with the aid of the cationic nature and small size, Ce6@WCS-IONP could effectively penetrate into MRSA biofilm, revealed by 3D fluorescence imaging. Both biomass analysis and viable bacteria counting demonstrated that Ce6@WCS-IONP showed potent biofilm ablation efficacy, averagely 7.1 log unit lower than that in free Ce6 group upon identical light irradiation. In addition, local treatment of MRSA-infected mice with Ce6@WCS-IONP plus light irradiation resulted in significant antibacterial and wound healing effect, accompanied by good biocompatibility in vivo. Collectively, photosensitizer-loaded cationic IONP with effective biofilm penetration and photodynamic eradication potential might be a promising nano platform in fighting against antibiotic-resistant microbial pathogen and biofilm.

Water-soluble chlorin e6-hydroxypropyl chitosan as a high-efficiency photoantimicrobial agent against Staphylococcus aureus.

The development of new antimicrobial agents is important to combat infections caused by pathogenic bacteria. Herein, Hydroxypropyl chitosan (HPCS), a hydrophilic modified product of chitosan (CS), was employed as a carrier of the photosensitizer chlorin e6 (Ce6) through an amide bond to obtain the products (HPCS-Ce6 conjugates) with a degree of substitution (DS) ranging from 2.95% to 5.25%. The UV-vis absorption spectra and 1H NMR spectra confirmed the successful synthesis of the products. The products have a better and more stable reactive oxygen species (ROS) generation capacity and higher bacterial affinity than Ce6. At a very low dose (1.8 µg/mL), the highest DS product (HPCS-Ce6-3) can effectively kill Staphylococcus aureus (S. aureus) under 660 nm irradiation. In addition, the HPCS-Ce6 conjugates showed high biocompatibility in the CCK-8 test. The HPCS-Ce6 conjugates could be a photodynamic antibacterial agent with good water solubility, high biocompatibility, and antibacterial activity.

Hydrogen Peroxide and Hypochlorite Responsive Fluorescent Nanoprobes for Sensitive Cancer Cell Imaging.

Accurate diagnosis of cancer cells directly affects the clinical treatment of cancer and can significantly improve the therapeutic effect of cancer patients. Cancer cells have a unique microenvironment with a large amount of peroxide inside, effectively differentiated from relevant microenvironment normal cells. Therefore, designing the high-sensitive probes to recognize and distinguish the special physiological microenvironment of cancer cells can shed light on the early diagnosis of cancers. In this article, we design and construct a fluorescence (FL) contrast agent for cancer cell recognition and imaging analysis. Firstly, luminol-gold NPs (Lum-AuNPs) have been initially built, and then successfully loaded with the fluorescent receptor Chlorin e6 (Ce6) to prepare the luminescent nanoprobes (Ce6@Lum-AuNPs) with green synthesis, i.e., with biocompatible agents and mild temperature. The as-prepared fluorescent Ce6@Lum-AuNPs can efficiently and sensitively realize FL bioimaging of cancer cells. The relevant bio-sensing mechanism pertains to the presence of hypochlorite (ClO-); hydrogen peroxide (H2O2) in cancer cells could readily interact with luminol to produce chemiluminescence, which can activate the Ce6 component to emit near-infrared (NIR) FL. Therefore, this raises the possibility of utilizing the Ce6@Lum-AuNPs as efficient fluorescent nanoprobes for promising cancer early diagnosis and other relevant disease bioanalysis.

Photoactive "Bionic Virus" Robustly Elicits the Synergy Anticancer Activity of Immunophotodynamic Therapy.

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.

Enhanced ROS-Boosted Phototherapy against Pancreatic Cancer via Nrf2-Mediated Stress-Defense Pathway Suppression and Ferroptosis Induction.

In situ oxygen generation is the most common strategy to boost reactive oxygen species (ROS) for enhancing the efficacy of phototherapy in cancer, including photodynamic therapy (PDT) and photothermal therapy (PTT). However, hyperoxidation or hyperthermia often triggers stress-defense pathways and promotes tumor cell survival, thus severely limiting the therapeutic efficacy. To overcome the tumor hypoxia and thermal resistance existing in phototherapy, we constructed a self-synergistic nanoplatform for tumors by incorporating brusatol, a nuclear factor erythroid 2-related factor (Nrf2) inhibitor, into the silica nanonetwork. It was then sequentially decorated with MnO2 and the photosensitizer chlorin e6 (Ce6) and then coated with poly(ethylene glycol)-folate (PEG-FA)-functionalized polydopamine (PDA) (designated as brusatol/silica@MnO2/Ce6@PDA-PEG-FA). As an oxygen generator, MnO2 can promote ROS production, which not only directly enhances Ce6-mediated PDT but also strengthens PDA-mediated PTT by attacking heat shock proteins (HSPs). Particularly, brusatol could efficiently inhibit the activation of Nrf2 defense pathway under hyperoxidation and hyperthermia and cause glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) inactivation, thereby inducing ferroptosis and ultimately enhancing the phototherapeutic effects. By exploiting these features, brusatol/silica@MnO2/Ce6@PDA-PEG-FA exhibited excellent antitumor efficacy with enhanced PDT and PTT both in in vitro and in vivo studies. Overall, our work highlights a promising strategy against hypoxia- and hyperthermia-associated resistance in phototherapy via suppressing stress-defense system and inducing ferroptosis.

Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy.

Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs in vivo. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of ∼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (∼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors in vivo. More excitingly, the Mn2+-chelating probe (Ce6-Leu@Mn2+) was demonstrated to have the capability to catalyze endogenous H2O2 to persistently release O2 at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment.

Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy.

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

Photo-Driven Delivery of 125I-Labeled Nanomicelles for Nucleus-Targeted Internal Conversion Electron-Based Cancer Therapy.

As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as 125I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C18-PMH-PEG)) to deliver 125I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C18-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C18-PEG/Cur nanoparticles. After labeling Cur with 125I, Ce6-C18-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C18-PEG/125I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of 125I-Cur to enter the nucleus. By this strategy, Ce6-C18-PEG/125I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize 125I delivery for tumor treatment.

Macrophages mediated delivery of chlorin e6 and treatment of lung cancer by photodynamic reprogramming.

Photodynamic therapy (PDT) is an emerging anti-tumor strategy.Photosensitizer chlorin e6 (Ce6) can induce photodynamic effect to selectively damage lung cancer cells.In order to further improve its tumor targeting ability, macrophages can be applied as carrier to deliver Ce6 to lung cancer.Tumor associated macrophages (TAM) are important immunocytes in lung cancer immune microenvironment. TAM play crucial role in tumor promotion due to the Immunosuppressive property, reprogramming phenotype of TAM therefore has become a promising strategy.Based on this, in the present study, we suppose that TAM can be used as carrier to deliver Ce6 to lung cancer and be reprogrammed to M1 phenotype by photodynamic action to mediate anti-lung cancer efficacy.The results showed TAM could load with Ce6 and keep viability in the absence of near infrared irradiation (NIR).Moreover, Its viability decreased little within 10 h after NIR.Ce6-loaded TAM could deliver Ce6 to lung cancer cells and retain some drugs in TAM per se.After NIR, phagocytosis of macrophages was enhanced. The expressions of GBP5, iNOS and MHC-II was up-regulated, which indicated TAM were polarized to M1 phenotype.Finally, the study also found the reprogrammed macrophages could inhibit the proliferation and promote the apoptosis of lung cancer cells.These results suggested that macrophages could deliver Ce6 to lung cancer and exhibit anti-lung cancer effect through photodynamic reprogramming.This study provides a novel approach for combining photodynamic action with anti-tumor immunotherapy.

Nanoliposomes co-encapsulating Ce6 and SB3CT against the proliferation and metastasis of melanoma with the integration of photodynamic therapy and NKG2D-related immunotherapy on A375 cells.

Purpose. To overcome the insufficiency of conventional photodynamic therapy (PDT) for treating metastatic melanoma, the combination of smart nanoparticles and PDT with immunotherapy was used to achieve a higher efficiency by accumulating more photosensitizers in tumor areas and triggering stronger immune responses against tumors after PDT.Methods. In this study, we designed a nanoliposome co-encapsulation of chlorin E6 (Ce6) and SB-3CT to realize significant antitumoral proliferation and metastasis efficacy after laser irradiation in A375 cells. The morphology, size distribution, and loading efficiency of Ce6-SB3CT@Liposome (Lip-SC) were characterized. The reactive oxygen species (ROS) generation and cytotoxicity were evaluated in A375 cells, and the mechanisms of natural killer (NK) cell-mediated killing were assessed.Results. Lip-SC showed good stability and was well-dispersed with a diameter of approximately 140 nm in phosphate-buffered saline. The nanoliposomes could accumulate in tumor areas and induce apoptosis in cancer cells upon 660 nm light irradiation, which could trigger an immune response and induce the expression of NK group 2 member D (NKG2D) ligands. The subsequently released SB-3CT could further activate NK cells effectively and strengthen the immune system by inhibiting the shedding of soluble NKG2D ligands.Discussion. Taken together, the synergistic effects of SB-3CT on nanoliposomes for Ce6-mediated PDT were analyzed in detail to provide a new platform for future anti-melanoma treatment.

Chlorophyllides: Preparation, Purification, and Application.

Chlorophyllides can be found in photosynthetic organisms. Generally, chlorophyllides have a-, b-, c-, d-, and f-type derivatives, and all chlorophyllides have a tetrapyrrole structure with a Mg ion at the center and a fifth isocyclic pentanone. Chlorophyllide a can be synthesized from protochlorophyllide a, divinyl chlorophyllide a, or chlorophyll. In addition, chlorophyllide a can be transformed into chlorophyllide b, chlorophyllide d, or chlorophyllide f. Chlorophyllide c can be synthesized from protochlorophyllide a or divinyl protochlorophyllide a. Chlorophyllides have been extensively used in food, medicine, and pharmaceutical applications. Furthermore, chlorophyllides exhibit many biological activities, such as anti-growth, antimicrobial, antiviral, antipathogenic, and antiproliferative activity. The photosensitivity of chlorophyllides that is applied in mercury electrodes and sensors were discussed. This article is the first detailed review dedicated specifically to chlorophyllides. Thus, this review aims to describe the definition of chlorophyllides, biosynthetic routes of chlorophyllides, purification of chlorophyllides, and applications of chlorophyllides.

Chitosan modified ultra-thin hollow nanoparticles for photosensitizer loading and enhancing photodynamic antibacterial activities.

Antibacterial photodynamic therapy (PDT) has attracted extremely attention due to not inducing bacteria to generate resistance. However, the poor utilization and low reactive oxygen species (ROS) field of photosensitizers hinder their further application for antibacterial. Here, we designed ultra-thin hollow silica nanoparticles (UHSN), followed by pore-engineering including covalent anchoring of chitosan (UHSN@CS) for enhanced loading and photodynamic property of photosensitizer. The UHSN@CS exhibit high loading efficiency (80.6%, pH = 6.0) and controllable pH-responsive release for Ce6. Additionally, UHSN@CS can enhance the ROS yield of photosensitizers and effectively adhere to S. aureus, thus enormously enhancing antibacterial performance toward bacteria. Moreover, UHSN@CS-Ce6 can obliterate mature S. aureus biofilm and cause an 81% decrease in the biomass, showing a better therapeutic effect than Ce6 (59.2%) under laser irradiation. In vivo results confirm that UHSN@CS-Ce6 is effective to promote infectious wound regeneration. As photodynamic-based nanoplatforms, UHSN@CS-Ce6 are potential antibacterial agents for skin infection therapy.

Photodynamic therapy using self-assembled nanogels comprising chlorin e6-bearing pullulan.

With minimal invasiveness and spatiotemporal therapeutic effects, photodynamic therapy is one of the most promising candidates for cancer treatment. Here, we developed a facile self-assembled nanogel using photosensitizer-grafted polysaccharides called chlorin e6-bearing pullulan. Chlorin e6 is used as a photosensitizer in cancer therapy. The anti-cancer effect of photodynamic therapy with our nanogel system was 780 times higher than that of the commercially available photosensitizer Photofrin. Finally, we demonstrated that actively growing cancer cell spheroids can be completely suppressed after treatment. Our system could efficiently induce tumor regression in tumor xenograft mice.

Targeted and oxygen-enriched polymeric micelles for enhancing photodynamic therapy.

Photodynamic therapy (PDT) has been emerged as an alternative therapeutic modality in treatment of several malignant tumors. However, the therapeutic efficacy of PDT is often limited by the solubility of photosensitizers, tumor hypoxia and lack of target specificity to cancer cells. In this study, we developed a folate-conjugated fluorinated polymeric micelle (PFFA) to deliver the hydrophobic photosensitizer (chlorin e6, Ce6) to overcome these limitations. The fluorinated micelles exhibit the low critical micelle concentration, good long-term stability, higher oxygen-carrying capacity and better singlet oxygen generation efficiency compared to non-fluorinated micelles, indicating the potential to improve the PDT efficacy in hypoxic conditions. Cytotoxicity of PDT effect and cellular uptake demonstrate the higher cell growth inhibition to HeLa cells upon irradiation attributed to the selective internalization of Ce6-loaded PFFA micelles (PFFA-Ce6). All results demonstrate the PFFA-Ce6 micelles with targeting function and oxygen-carrying capacity can serve as a promising drug delivery system for hydrophobic photosensitizers and improvement on PDT efficacy.

Photodynamic inactivation of planktonic Staphylococcus aureus by sodium magnesium chlorophyllin and its effect on the storage quality of lettuce.

Photodynamic inactivation (PDI) is a fast and effective non-heat sterilization technology. This study established an efficient blue light-emitting diode (LED) PDI with the photosensitizer sodium magnesium chlorophyllin (SMC) to eradicate Staphylococcus aureus in food. The antibacterial mechanisms were determined by evaluating DNA integrity, protein changes, morphological alteration, and the potency of PDI to eradicate S. aureus on lettuce was evaluated. Results showed that planktonic S. aureus could not be clearly observed on the medium after treatment with 5.0 µmol/L SMC for 10 min (1.14 J/cm2). Bacterial cell DNA and protein were susceptible to SMC-mediated PDI, and cell membranes were found to be disrupted. Moreover, SMC-mediated PDI effectively reduced 8.31 log CFU/mL of S. aureus on lettuce under 6.84 J/cm2 radiant exposure (30 min) with 100 µmol/L SMC, and PDI displayed a potent ability to restrain the weight loss as well as retard the changes of color difference of the lettuce during 7 day storage. The study will enrich our understanding of the inactivation of S. aureus by PDI, allowing for the development of improved strategies to eliminate bacteria in the food industry.