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Wound-associated infections represent an arduous global healthcare challenge, especially in the "post-antibiotic" era, necessitating the development of advanced antimicrobial dressing materials that simultaneously dictate the use of rapid yet effective disinfection, low drug resistance and side effects, and the potency to foster tissue healing. Nanoantimicrobial-armored nanostructured functional dressing systems have piqued extensive interest to satisfy these criteria. Herein, fusing electrospinning nanotechnology and an emerging photo–chemo synergistic sterilization paradigm, a smart "all-in-one" multifunctional wound-managing dressing platform was constructed, through incorporating photochemically active nanocrystalline cuprous oxide (Cu2O) into modified polycaprolactone (mPCL) electrospun fibrous mats. The resulting materials were systematically characterized pertaining to physiochemical analysis, photoabsorption and photocurrent measurements, and photocatalytic reactive oxygen species (ROS) generation. The capability of this nanoplatform to elicit rapid, photoactivated, catalytically augmented bacterial disinfection was corroborated, displaying ∼99–100% broad-spectrum antibacterial efficacies against Staphylococcus aureus and Escherichia coli in 25 min. Benefiting from the release of Cu2+, mPCL-Cu2O impairs bacterial contamination even under dark conditions. Furthermore, these materials also exhibited favorable in vitro/-ovo biocompatibility toward NIH3T3 fibroblasts, red blood cells, and chick chorioallantoic membrane, alongside appreciable pro-healing capacity in bridging scratch-based wounds, which could be attributed to nanofiber-afforded biomimetic topography and controllable liberation of micronutrient Cu ions. This study provides insights into the design and fabrication of simple yet smart antibacterial nanoplatforms for biomedical applications. [ABSTRACT FROM AUTHOR]

How to develop antitumor nanodrugs with low toxicity and a good curative effect is an urgent problem in the current biomedicine field. In this work, different proposed composites were simulated by the finite difference time domain (FDTD) and COMSOL, including the material element, refractive index, particle size, and shape. Also, different machine learning algorithms are utilized to predict the absorbance at the near-infrared laser of 980 nm of different materials. Through train, validation, and test, the prediction of the as-synthesized Pt–Mn has high absorbance. Then, inorganic Pt–Mn was coated with PEI in order to improve their biocompatibility. Pt–Mn nanoparticles can generate ROS under the single 980 nm laser irradiation as a photodynamic therapy (PDT) agent and as a photothermal therapy (PTT) agent to heat the cells with a photothermal conversion efficiency of 23.6%. In addition, the electrochemical and in vitro chemodynamic therapy (CDT) experiments prove that Pt–Mn nanozymes could mimic the activity of peroxidase and enhance the Fenton reaction, thereby catalyzing excess H2O2 to produce hydroxyl free radicals and illustrating the potential to induce tumor cell apoptosis as the CDT agent in a weakly acidic tumor environment to complete high-efficiency chemokinetic therapy. Finally, Pt–Mn–PEI nanoparticles were used for PDT/PTT/CDT and the immune checkpoint inhibitor of anti-PD-L1 is injected in order to obtain the assistant immunotherapy, providing a potential choice to anticancer through effective synergistic cancer therapies. [ABSTRACT FROM AUTHOR]

Nosocomial infections are a significant threat to public health that leads to substantial morbidity and mortality. The emergence and spread of antibiotic-resistant organisms have compounded the complexity of managing these infections, highlighting the urgent need for innovative and effective strategies to combat them. Photostimuli-responsive nanomaterials have emerged as promising tools for coating biomedical devices and tools against nosocomial infections due to their ability to selectively target and kill pathogenic bacteria and fungi. It is feasible to develop antibacterial surfaces by integrating photothermal agents (PTAs), photodynamic agents (PDAs), and both PTAs and PDAs into coatings. When exposed to light, PTAs generate heat that can be used to kill bacteria, while PDAs emit reactive oxygen species (ROS) that can also be used to kill bacteria. The combination of photothermal and photodynamic therapies produces a synergistic effect in which the death of bacteria is boosted in comparison with the use of each individual therapy. These coatings have the potential to provide enhanced bacterial control for a number of biomedical devices, including implants, catheters, meshes, and wound dressings. The utilization of antimicrobial nanomaterials offers a promising approach for reducing the risk of infections associated with the use of these devices. [ABSTRACT FROM AUTHOR]

The clinical application of photodynamic therapy (PDT) is hampered by the suboptimal tumor-targeting properties of photosensitizers (PSs) and the presence of abundant antioxidants in cancer cells. To overcome these limitations, in this study, we proposed a formulation of an Ir-(III) complex into a promising tumor-targeted coordination polymer (Ir-PB), which could self-assemble into nanoparticles (Ir-PB NPs) for bioimaging and tumor-targeted PDT. Ir-PB NPs were found to efficiently target A549 cells and specifically accumulate in the mitochondria. Under light irradiation (400 nm, 10 mW/cm2, 15 min), Ir-PB NPs could trigger cell death through a combination of apoptosis and ferroptosis pathways by the photoinduced depletion of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) and the photoinduced production of single oxygen (1O2). The mechanisms featured the attenuation of the antioxidant capacity of tumor cells, the reduction of mitochondrial membrane potential (MMP), decrease in ATP production, activation of Caspase-3 protein, accumulation of lipid peroxidation (LPO), shrinkage of mitochondria, and down-regulation of glutathione peroxidase 4 (GPX4). The effectiveness of Ir-PB NPs in inhibiting tumor growth upon light irradiation was confirmed using an A549 xenograft mouse model. This study presents a promising strategy for developing photodynamic drugs that have excellent tumor-targeting abilities and enhance the efficiency of PDT. [ABSTRACT FROM AUTHOR]

Damaged skin is susceptible to invasion by harmful microorganisms, especially Staphylococcus aureus and Escherichia coli , which can delay healing. Epigallocatechin-3-gallate (EGCG) is a natural compound known for effectively promoting wound healing and its potent anti-inflammatory effects. However, its application is limited due to its susceptibility to oxidation and isomerization, which alter its structure. The use of zeolitic imidazolate framework-8 (ZIF-8) can effectively tackle these issues. This study introduces an oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) self-supplying ZIF-8 nanoplatform designed to enhance the bioavailability of EGCG, combining photodynamic therapy (PDT) and chemodynamic therapy (CDT) to improve antibacterial properties and ultimately accelerate wound healing. For this purpose, EGCG and indocyanine green (ICG), a photosensitizer, were successively integrated into a ZIF-8, and coated with bovine serum albumin (BSA) to enhance biocompatibility. The outer layer of this construct was further modified with manganese dioxide (MnO 2 ) to promote CDT and calcium peroxide (CaO 2 ) to supply H 2 O 2 and O 2 , resulting in the final nanoplatform EGCG-ICG@ZIF-8/BSA-MnO 2 /CaO 2 (EIZBMC). In in vitro experiments under 808 nm laser, EIZBMC exhibited synergistic antibacterial effects through PDT and CDT. This combination effectively released reactive oxygen species (ROS), which mediated oxidative stress to inhibit the bacteria. Subsequently, in a murine model of wound infection, EIZBMC not only exerted antibacterial effects through PDT and CDT but also alleviated the inflammatory condition and promoted the regeneration of collagen fibers, which led to accelerated wound healing. Overall, this research presents a promising approach to enhancing the therapeutic efficacy of EGCG by leveraging the synergistic antibacterial effects of PDT and CDT. This multifunctional nanoplatform maximizes EGCG's anti-inflammatory properties, offering a potent solution for promoting infected wound healing.

Tetraphenyloporphyrin derivatives are a useful scaffold for developing new pharmaceuticals for photodynamic therapy (PDT) and the photodiagnosis (PD) of cancer. We synthesized new sulfonamide fluorinated porphyrin derivatives and investigated their potential as photosensitizers and real-time bioimaging agents for cancer. We found that 5,10,15,20-tetrakis-[2',3',5',6'-tetrafluoro-4'-methanesulfamidyl)phenyl]bacteriochlorin ( F 4 BMet ) has intense absorption and fluorescence in the near-infrared, efficiently generates singlet oxygen and hydroxyl radicals, has low toxicity in the dark, and high phototoxicity. We increased its bioavailability with encapsulation in Pluronic-based micelles, which also improved the photodynamic effect. F 4 BMet exhibits pH-dependent properties (lower pH promoted its aggregation), and a GlyGly buffer was used to effectively solubilize the compound. In vitro findings with 2D cell culture were complemented with human-induced pluripotent stem cell (hiPSC)-derived organoids. F 4 BMet in P123 micelles showed enhanced efficacy compared to F 4 BMet in the GlyGly formulation. F 4 BMet was further evaluated in real-time bioimaging and PDT of BALB/c mice bearing CT26 tumors. After i.v. injection, the photosensitizer was visible in the tumor area 3 h after injection. The most successful therapeutic approach proved to be tumor-targeted PDT using P123-encapsulated F 4 BMet illuminated 24 h after administration with a light dose of 42 J/cm 2 , which led to a 30% long-term cure rate.

Two phthalocyanine derivatives tetra-peripherally substituted with tert -butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO 2 t Bu demonstrated an outstanding ability to generate singlet oxygen (Φ Δ = 0.87-0.99), while ZnSO 2 t Bu in addition to 1 O 2 (Φ Δ = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log P ow ) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of ZnSO 2 t Bu and 100% of PtSO 2 t Bu- treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO 2 t Bu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.

The sustained rapid growth of tumor cells depends directly on the activity of mitochondria, which are important targets for many cancer drugs. Here, we report on a self-targeting method for mitochondria, a high atom efficiency nanoplatform, Mn/HA-CDs, made from hyaluronic acid-derived carbon dots (HA-CDs) and Mn2+ in a coordination structure of Mn-N5. We found that the Mn/HA-CDs with atomically dispersed Mn (0.73%) can generate reactive oxygen species (ROS) with a high atom economy. Particularly, its singlet oxygen (1O2) quantum yield (0.40) is 3 times higher than that of the previous HA-CDs (0.13). Active absorption of Mn/HA-CDs by mitochondria inhibits mitochondrial superoxide dismutase (SOD) enzyme function, intensifies ROS damage to the mitochondria, and eventually promotes the photodynamic therapy (PDT) effect on tumor cells. Our findings suggest that targeting mitochondria with single-atom metal-anchored CDs for a better PDT effect is a viable method of treating tumors. [ABSTRACT FROM AUTHOR]

Phototherapies are promising for noninvasive treatment of aggressive tumors, especially when combining heat induction and oxidative processes. Herein, we show enhanced phototoxicity of gold shell-isolated nanorods conjugated with toluidine blue-O (AuSHINRs@TBO) against human colorectal tumor cells (Caco-2) with synergic effects of photothermal (PTT) and photodynamic therapies (PDT). Mitochondrial metabolic activity tests (MTT) performed on Caco-2 cell cultures indicated a photothermal effect from AuSHINRs owing to enhanced light absorption from the localized surface plasmon resonance (LSPR). The phototoxicity against Caco-2 cells was further increased with AuSHINRs@TBO where oxidative processes, such as hydroperoxidation, were also present, leading to a cell viability reduction from 85.5 to 39.0%. The molecular-level mechanisms responsible for these effects were investigated on bioinspired tumor membranes using Langmuir monolayers of Caco-2 lipid extract. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) revealed that the AuSHINRs@TBO incorporation is due to attractive electrostatic interactions with negatively charged groups of the Caco-2 lipid extract, resulting in the expansion of surface pressure isotherms. Upon irradiation, Caco-2 lipid extract monolayers containing AuSHINRs@TBO (1:1 v/v) exhibited ca. 1.0% increase in surface area. This is attributed to the generation of reactive oxygen species (ROS) and their interaction with Caco-2 lipid extract monolayers, leading to hydroperoxide formation. The oxidative effects are facilitated by AuSHINRs@TBO penetration into the polar groups of the extract, allowing oxidative reactions with carbon chain unsaturations. These mechanisms are consistent with findings from confocal fluorescence microscopy, where the Caco-2 plasma membrane was the primary site of the cell death induction process.

Pathogenic bacteria infections bring about a substantial risk to human health. Given the development of antibiotic-resistance bacteria, alternative antibacterial strategies with great inactivation efficiency and bacteria-binding ability are extremely attractive. In this work, a metabolic labeling photosensitizer, prepared by the coupling of commercial IR820 and d-propargylglycine (a type of d-amino acid, DAA) via a straightforward one-step incubation (IR820-DAA), could metabolically be incorporated into the bacterial wall via enzymatic reactions, thus enhancing antibacterial efficiency. The laser energy at 808 nm could make IR820-DAA a synergistic photothermal/photodynamic agent for efficient antibacterial therapy and wound healing. Furthermore, IR820-DAA exhibits good water solubility and biological safety for clinical translation and even possesses biofilm degradation activity toward methicillin-resistant Staphylococcus aureus ( MRSA ). Overall, the proposed IR820-DAA holds great promise as a nonantibiotic tool for the treatment of bacteria-related diseases and offers a blueprint for building the precise synergistic antibacterial therapeutic platform.

As for effective multimodal phototheranostic AIEgens, it is important to find strategies for manipulating photophysical dissipation to achieve optimized performance. Herein, a "all-in-one" phototheranostic AIEgen, ( E )-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)naphtho[1,2- d ]thiazol-1-ium-1-yl)propane-1-sulfonate (NS-STPA) was constructed by a rigid coplanar grafting flexible rotor. NS-STPA nanoparticles (NPs) exhibited NIR fluorescent luminescence (FL) with φ FL 2.78%. Upon 660 nm irradiation, the high photothermal conversion efficiency (39.01%) and effective reactive oxygen species (ROS) generation (5.28 times to Ce6) indicated the nonradiative decays are valuable in phototherapy. High • OH outputs showed NS-STPA NPs were outstanding type I ROS generators. The twisted D-A structure induced a large spin-orbit coupling (SOC), and insertion of thiophene decreased the S 1 -T 1 energy gap (Δ E ST ). The nanoaggregate prolonged the triplet-state lifetime (τ T ). These all facilitate the intersystem crossing (ISC) for NS-STPA NPs. The photoinduced electron transfer resulted in • O 2 - and then • OH generation. In vivo evaluation indicated the promising application of NS-STPA NPs in FL and photothermal dual imaging-guided synergistic photodynamic and photothermal therapies.

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O 2 and H 2 O 2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co 2+ and release CaO 2 and graphene quantum dots (GQDs). The exposed CaO 2 reacted with water to generate H 2 O 2 and O 2 . The self-supplied O 2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H 2 O 2 was catalyzed by endogenous Co 2+ to produce hydroxyl radicals for Co 2+ -triggered CDT. In vitro and in vivo experiments confirm that CaO 2 /GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO 2 /GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO 2 /GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway.

Photodynamic therapy (PDT) presents an alternative noninvasive therapeutic modality for the treatment of cancer and other diseases. PDT relies on cytotoxic singlet oxygen (reactive oxygen species or ROS) that is locally generated through energy transfer between a photosensitizer (PS) and molecularly dissolved triplet oxygen. While a number of nanoparticle-based PS vehicles have been described, because of their beneficial and proven biodistribution and pharmacokinetic profiles, ultrasmall nanoparticles with diameters below 10 nm are particularly promising. Here, we investigate two different particle designs deviating from ultrasmall poly(ethylene glycol)-coated (PEGylated) fluorescent core-shell silica nanoparticles referred to as Cornell prime dots (C' dots) by replacing the fluorescent dye with a photosensitizer (psC' dots), here the methylene blue (MB) derivate MB2. In the first approach (design 1), MB2 is encapsulated into the matrix of the silica core, while in the second approach (design 2), MB2 is grafted onto the silica core surface in between chains of the sterically stabilizing poly(ethylene glycol) (PEG) corona. We compare both cases with regard to their singlet oxygen quantum yields, Φ Δ , with the effective Φ Δ eff per particle reaching 111 ± 3 and 161 ± 5% for designs 1 and 2, respectively, substantially exceeding single MB2 molecule performance. Encapsulation significantly improves PS photostability, while surface conjugation diminishes it, relative to free MB2. Finally, we show that both particle designs allow functionalization with a targeting peptide, cyclo(Arg-Gly-Asp-D-Tyr-Cys) [c(RGDyC)]. Results suggest that psC' dots are a promising targeted platform for PDT applications, e.g. in oncology, that may combine colloidal stability, efficient renal clearance limiting off-target accumulation, targeted delivery to sites of disease, and effective ROS generation maximizing therapeutic efficacy.

Photoactive theranostics including photodynamic therapy (PDT) hace aroused an intensive interest that combines medical diagnostics with treatment under a single irradiation laser. However, the conventional organic PDT agents usually suffer from aggregation caused by the quenching effect. In this research, we designed a core-shell-shell (CSS) UCNPs with NaGdF 4 as the host, and the UCNPs could emit higher blue/green light by the energy transfer processes among Nd/Yb/Tm/Gd/Tb under 808 nm laser. When the CSS UCNPs were combined with the MnO 2 semiconductor as the energy acceptor, CSS@Mn could be utilized as an effective PDT agent under a NIR laser. The temperature also increased more than 12.2 °C under the 808 nm laser, indicating the potential of synergistic photothermal therapy (PTT) and PDT. Interestingly, cells with small amounts of H 2 O 2 could be responsive to the CSS@Mn platform. The antitumor effect was proved by the in vitro and in vivo experiments. Also, the biocompatibility, biodistribution, and excretion pathway were detected and revealed by the H&E stained pathological section and photoacoustic (PA) images. That means this platform could be potentially used as antitumor PDT/PTT agents.

The cell membrane is the protecting frontier of cells, which is crucial for maintaining cell integrity, and has a close relationship with cell growth and death. There is a growing need for cell membrane imaging and monitoring in both living and dying cells. Herein, we report a new amphiphilic tetraphenylethene-based pyridinium salt (TPE-MEM) with aggregation-induced emission features for discriminatory cell membrane imaging. The fluorogenic probe with high yield was synthesized following asymmetric McMurry reaction, Williamson ether synthesis reaction, Suzuki coupling, and aldol condensation between a double-charged pyridinium salt and hexyloxytetraphenylethene benzaldehyde. TPE-MEM shows good water solubility, biocompatibility, and cell membrane specificity. Interestingly, a reactive oxygen species (ROS) is produced by the molecule (TPE-MEM) under room-light irradiation, which could destroy the integrity of the plasma membrane and cause cell necrosis. This enables a visible observation of cell necrosis and the phototherapeutic effect under a mild condition. Preliminary animal investigations also demonstrated the photodynamic therapy (PDT) effectiveness of TPE-MEM in tumor growth inhibition. We conclude that TPE-MEM is potentially a cell membrane-selective photosensitizer for PDT and it is worthy of further exploration of the phototherapeutic effect on animals systematically.

Nucleolus tracking and nucleus-targeted photodynamic therapy are attracting increasing attention due to the importance of nucleolus and the sensitivity of nucleus to various therapeutic stimuli. Herein, a new class of multifunctional fluorescent carbon quantum dots (or carbon dots, CDs) synthesized via the one-pot hydrothermal reaction of m-phenylenediamine and l-cysteine was reported to effectively target nucleolus. The as-prepared CDs possess superior properties, such as low-cost and facile synthesis, good water dispersibility, various surface groups for further modifications, prominent photostability, excellent compatibility, and rapid/convenient/wash-free staining procedures. Besides, as compared with SYTO RNASelect (a commonly used commercial dye for nucleolus imaging) that can only image nucleolus in fixed cells, the CDs can realize high-quality nucleolus imaging in not only fixed cells but also living cells, allowing the real-time tracking of nucleolus-related biological behaviors. Furthermore, after conjugating with protoporphyrin IX (PpIX), a commonly used photosensitizer, the resultant CD-PpIX nanomissiles showed remarkably increased cellular uptake and nucleus-targeting properties and achieved greatly enhanced phototherapeutic efficiency because the nuclei show poor tolerance to reactive oxygen species produced during the photodynamic therapy. The in vivo experiments revealed that the negatively charged CD-PpIX nanomissiles could rapidly and specifically target a tumor site after intravenous injection and cause efficient tumor ablation with no toxic side effects after laser irradiation. It is believed that the present CD-based nanosystem will hold great potential in nucleolus imaging and nucleus-targeted drug delivery and cancer therapy.

Photodynamic therapy (PDT) is a promising therapeutic modality for cancer. However, current protocols using bare drugs suffer from several limitations that impede its beneficial clinical effects. Here, we introduce a new approach for an efficient PDT treatment. It involves conjugating a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, to gold nanoparticles (AuNPs) that serve as carriers for the drug. AuNPs have a number of characteristics that make them highly suitable to function as drug carriers: they are biocompatible, serve as biomarkers, and function as contrast agents in vitro and in vivo. We synthesized AuNPs and covalently conjugated the mTHPC drug molecules through a linker. The resultant functional complex, AuNP-mTHPC, is a stable, soluble compound. SH-SY5Y human neuroblastoma cells were incubated with the complex, showing possible administration of higher doses of drug when conjugated to the AuNPs. Then cells were irradiated with a laser beam at 650 nm to mimic the PDT procedure. Our study shows higher rates of cell death in cells incubated with the AuNP-mTHPC complex compared to the incubation with the free drug. Using the new complex may form the basis for a better PDT strategy for a wide range of cancers.

The development of agents for noninvasive photothermal/photodynamic therapies (PTT/PDT) against cancer remains challenging because most PTT agents cause side effects on normal tissues due to their high cytotoxicity and slow metabolism rate. We successfully synthesized an organic compound (C3), encapsulated in PEG-PCL with indocyanine green (ICG), to form hybrid nanoparticles (PEG-PCL-C3-ICG NPs) for use as a new PPT/PDT agent to treat cancer with a single irradiation. Compared with conventional PPT agents, such as Au nanorods, C3 showed better photothermal conversion stability, lower cytotoxicity and a faster metabolic rate, ensuring promising PTT efficacy in eliminating tumors during in vivo application, while ICG was used as a PDT agent. With 808 nm laser irradiation at tumor sites, the PEG-PCL-C3-ICG NPs were able to simultaneously produce hyperthermia through C3 and produce reactive oxygen species as well as a fluorescence-guided effect through ICG to kill oral squamous cell carcinoma (OSCC) cells. The combination of these hypotoxic and metabolic hybrid nanoparticles with radiation therapy has potential for the future treatment of OSCC.

An efficient pH-responsive multifunctional polypeptide micelle for simultaneous imaging and in vitro photodynamic therapy (PDT) has been prepared. The goal here is to detect and treat cancer cells by near-infrared fluorescence (NIRF) imaging and PDT synchronously. A photosensitizer BODIPY-Br2 with efficient singlet oxygen generation was synthesized at first which owns both seductive abilities in fluorescence emission and reactive oxygen species (ROS) generation under light irradiation. Then, amphiphilic copolymer micelles pH-triggered disassembly were synthesized from N-carboxyanhydride (NCA) monomer via a ring-opening polymerization and click reaction for the loading of BODIPY-Br2 by hydrophobic interaction, and the driving force is the protonation of the diisopropylethylamine groups conjugated to the polypeptide side chains. In vitro tests performed on HepG2 cancer cells confirm that the cell suppression rate was improved by more than 40% in the presence of light in the presence of an extremely low energy density (12 J/cm(2)) with very low concentration of 5.4 μM photosensitizer. At the same time, the internalization of the nanoparticles by cells can also be traced by NIRF imaging, indicating that the NIR nanoparticles presented imaging guided photodynamic therapy properties. It provides the potential of using polypeptide as a biodegradable carrier for NIR image-guided photodynamic therapy.

Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS-biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy. This novel photomedicine consisted of a PD-NP core and a PS-conjugated hyaluronic acid (PS-HA) shell. The PD-NP and the PS-HA play roles as a quencher for PSs and a cancer targeting moiety, respectively. The synthesized PS-HA-shielded PD-NPs (PHPD-NPs) had a relatively narrow size distribution (approximately 130 nm) with uniform spherical shapes. In response to cancer-specific intracellular enzymes (e.g., hyaluronidase), the PHPD-NPs exhibited an excellent singlet oxygen generation capacity for PDT. Furthermore, an efficient photothermal conversion ability for photothermal therapy (PTT) was also shown in the PHPD-NPs system. These properties provide superior therapeutic efficacy against cancer cells. In mice tumor model, the photoactive restorative effects of the PHPD-NPs were much higher in cancer microenvironments compared to that in the normal tissue. As a result, the PHPD-NPs showed a significant antitumor activity in in vivo mice tumor model. The nanoparticle photomedicine design is a novel strategy for effective tumor therapy.

Small size molybdenum disulfide (MoS2) quantum dots (QDs) with desired optical properties were controllably synthesized by using tetrabutylammonium-assisted ultrasonication of multilayered MoS2 powder via OH-mediated chain-like Mo-S bond cleavage mode. The tunable up-bottom approach of precise fabrication of MoS2 QDs finally enables detailed experimental investigations of their optical properties. The synthesized MoS2 QDs present good down-conversion photoluminescence behaviors and exhibit remarkable up-conversion photoluminescence for bioimaging. The mechanism of the emerging photoluminescence was investigated. Furthermore, superior (1)O2 production ability of MoS2 QDs to commercial photosensitizer PpIX was demonstrated, which has great potential application for photodynamic therapy. These early affording results of tunable synthesis of MoS2 QDs with desired photo properties can lead to application in fields of biomedical and optoelectronics.

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs.

Translocator protein (TSPO) 18 kDa overexpression has been observed in a large variety of human cancers, especially breast cancers. PK 11195, an isoquinoline analogue, is one of the ligands of highest TSPO binding affinity. Due to the long biological half life of our photosensitizers, there is a need to label them with a long lived radioisotope, for example I-124. Our objectives are to find translocator protein targeted photosensitizers for both tumor imaging (PET) and photodynamic therapy (PDT). I-PK 11195 is conjugated with the tumor avid photosensitizer HPPH. We find that those two tumor avid components complement each other and make the conjugate molecule even more tumor avid; compared to the photosensitizer itself, the conjugate is found to show improved PDT efficacy. It is concluded that I-PK 11195 can be a good vehicle to deliver radionuclide and photosensitizer to TSPO overexpressed tumor regions. Such conjugates could be useful for both tumor imaging (PET) and PDT.