Glutathione-depleting mitochondria-targeting nanodrugs for stress amplification and immune activation via synergistic photodynamic therapy and cuproptosis.

Herein, we have developed a composite antibacterial hydrogel with photodynamic therapy (PDT) and photothermal therapy (PTT) antibacterial capabilities, triggered by white light and NIR light irradiation. A water-insoluble conjugated polymer (PDPP) with photothermal ability was prepared into nanoparticles by the nanoprecipitation method, and the cell-penetrating peptide TAT was grafted on the surface of the nanoparticles. Based on our previous work that developed a hybrid hydrogel with an enhanced PDT effect from polyisocyanide (PIC) hydrogel and cationic conjugated polythiophene (PMNT), PDPP nanoparticles (CPNs-TAT) with photothermal ability are introduced to realize the synergistic antibacterial effect of PDT and PTT. Using the PIC hydrogel to combine PIC and CPNs-TAT has the following advantages. First, the PIC hydrogel can regulate the aggregation state of PMNT, making it better dispersed and improving its capacity of reactive oxygen species (ROS) production. Second, CPNs-TAT can be uniformly dispersed in the PIC hybrid, thereby avoiding the toxicity caused by too high local concentration, achieving a uniform increase in system temperature, and enhancing the therapeutic effect of PTT. Third, the PIC hybrid has the synergistic treatment effect of PDT and PTT. The PIC hybrid intelligently regulates its antibacterial ability through white light and NIR light, which can be used in the white light and NIR light areas. When irradiated with white light and NIR light sequentially, synergistic PDT and PTT exhibit stronger antibacterial ability than PDT or PTT alone. The combination of two antibacterial methods realizes the dual-control antibacterial hydrogel of PDT and PTT and provides an antibacterial mode based on PIC hybrids. Therefore, the PIC hybrids are promising as an antibacterial excipient for clinical wounds.

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium–porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (1O2) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high 1O2 generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC50) (0.057 μM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium–porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Oxygen-economizing liposomes for synergistic photodynamic and starvation therapy

Photodynamic therapy (PDT) has been extensively investigated as an alternative cancer treatment; however, its efficacy is limited by the low oxygen content and excess glutathione (GSH) in tumor tissues. With the emergence of ferroptosis, which also impacts redox homeostasis, a combined PDT-ferroptosis approach holds promise for amplifying the efficacy of both treatments. However, concerns persist regarding biocompatibility and tumor-specific release. Here, we report a self-motivated co-nanoassembly for combined PDT and ferroptosis-driven tumor therapy. We first modify linoleic acid with protoporphyrin IX to form a lipidic derivative (denoted as PLA) and develop a light-boosted carrier-free nanoplatform (PLA@R NPs) by co-assembling the ferroptosis inducer RAS-selective lethal 3 (RSL3) and PLA. Upon light irradiation, reactive oxygen species produced by PDT trigger linoleic acid peroxidation, leading to the destruction of the nanoparticles and the release of RSL3. The rapid release of RSL3 enhances PDT sensitivity by depleting GSH and utilizing the Fenton reaction to supplement oxygen. Additionally, PDT accelerates lipid peroxidation, further inducing ferroptosis. This self-motivated effect increases oxidative stress in tumor tissues, as confirmed by a tumor-on-a-chip model. Moreover, the <i>in vivo</i> therapeutic effect with the PLA@R NPs is significant, demonstrating the promising potential of combining PDT and ferroptosis using a light-boosted and self-motivated nanoplatform.

Photodynamic therapy (PDT) is a clinically approved and minimally invasive form of cancer treatment. However, due to hypoxia at the tumor site and phototoxicity to normal tissues, monotherapies using photosensitizers remain suboptimal. This study aimed to develop a highly selective controlled catalase-enhanced synergistic photodynamic and photothermal cancer therapy based on gold nanostars.Methods: Gold nanostars (GNS) with high thermal conversion efficiency were used as the core for photothermal therapy (PTT) and the shell consisted of the photosensitizer Ce6-loaded mesoporous silicon. The shell was modified with catalase (E), which catalyzes the conversion of hydrogen peroxide to oxygen at the tumor site, alleviating hypoxia and increasing the effect of the photodynamic treatment. Finally, a phospholipid derivative with c(RGDyK) was used as the targeting moiety and the nanoparticle-encapsulating material.Results: The nanoprobe exhibited good dispersion, high stability, and high photothermal conversion efficiency (~28%) for PTT as well as a photodynamic "on-off" effect on Ce6 encapsulated in mesoporous channels. The "release" of Ce6 was only triggered under photothermal stimulation in vivo. Due to its targeting ability, 72 h after injection of the probe, the tumor site in mice showed an observable CT response. The combined treatment using photothermal therapy (PTT) and catalase-enhanced photo-controlled PDT exerted a superior effect to PTT or PDT monotherapies.Conclusion: Our findings demonstrate that the use of this intelligent nanoprobe for CT-targeted image-guided treatment of tumors with integrated photothermal therapy (PTT) and catalase-enhanced controlled photodynamic therapy (PDT) may provide a novel approach for cancer theranostics.

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly, in vitro results confirmed that combined PTT and PDT have exhibited better anticancer effect than PTT alone upon 808 nm laser irradiation. These results showed that the self-assembled BODIPY-HA NPs may be a promising nanomedicine for synergistic cancer PDT and PTT.

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer

Photo-responsive hollow silica nanoparticles for light-triggered genetic and photodynamic synergistic therapy

Bioorthogonal chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy

In the present study, plasmonic liposomes (PLs) loaded with photosensitizers were developed for synergistic photodynamic and photothermal therapy. These PLs were prepared by incorporating a photosensitizer, ZnPc, into the liposomal membrane for photodynamic therapy (PDT) and coating a gold nanofilm onto the surface for photothermal therapy (PTT). The gold coating was optimized to efficiently absorb the wavelength of light at which ZnPc is activated for PDT. The photosensitizing effect of ZnPc was synergistically enhanced upon single light irradiation due to local photothermal heating and the surface plasmon resonance of the gold nanostructure. Furthermore, combined photodynamic and photothermal therapy using ZnPc-PLs exhibited a remarkably enhanced therapeutic efficacy on cancer cells in vitro compared to PDT or PTT alone. Therefore, we believe that this dual photoactive nanodevice with a synergistic therapeutic index has great potential to improve the current phototherapy of cancer.

Achieving an integrated system for combinational therapy of cancer with enhanced efficacy is always a challenge. A multifunctional system (CCeT nanoparticles (NPs)) for a synergistic photodynamic and photothermal cancer therapy was successfully developed. This system is composed of Cu2- xS nanoclusters functionalized with chlorin e6 (Ce6)-conjugated branched polyethylenimine (PEI-Ce6) and mitochondria-targeting 3-(carboxypropyl)triphenylphosphonium bromide (TPP-COOH). The colocalization of the resulted CCeT NPs inside the mitochondria of cancer cells was proven. The CCeT NPs exhibited significant photodynamic therapy (PDT) efficacy due to efficient singlet oxygen (1O2) generation triggered by a 630 nm laser. This system also showed excellent photothermal conversion capability upon the irradiation of 808 nm laser for photothermal therapy (PTT). In particular, the platform achieved nearly 100% inhibitory rate of the tumor growth in vivo through combinational PDT and PTT. Thus, the CCeT NPs could efficiently inhibit the tumor growth in vitro and in vivo by combinational PDT and PTT, offering synergistic therapeutic efficiency as compared to PTT or PDT alone.

Polyelectrolyte wrapped methylation morpholine-phthalocyanine@gold nanorod for synergistic photodynamic therapy and photothermal therapy photodegradation of DNA

Synergistic in vivo photodynamic and photothermal antitumor therapy based on collagen-gold hybrid hydrogels with inclusion of photosensitive drugs

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications

Mitochondria and plasma membrane dual-targeted chimeric peptide for single-agent synergistic photodynamic therapy