Ru-loaded snowflake-like digenite nanozymes for bacterial eradication through synergistic photothermal and catalytic therapy.

Combined chemodynamic/photothermal therapy has great potential in tumor treatment. However, the presence of excessive glutathione (GSH) in the tumor microenvironment (TME) can attenuate its therapeutic effect, and other components in the TME have not been fully utilized as well. In this article, we designed a noble metal nanozyme called PdCu@BSA, which can be used for the combined chemodynamic therapy (CDT) and photothermal therapy (PTT) of tumor. In detail, PdCu@BSA has three different types of enzyme-like activities. Its catalase (CAT)-like activity can degrade extra H2O2 in the TME to create O2 and relieve the hypoxic situation. The glutathione oxidase (GSHox)-like activity can consume high level of GSH in the TME to reduce the consumption of reactive oxygen species (ROS). Peroxidase (POD)-like activity catalyzes H2O2 to form strong oxidized ·OH. The above enzyme-like activities enhance the effectiveness of CDT. Besides, PdCu@BSA has good photothermal effect and can be used for PTT when exposed to 1064 nm laser. Therefore, based on multiple enzyme-like activities and photothermal effects, PdCu@BSA can be employed for synergistic tumor therapy, resulting in good therapeutic outcome.

A "simple" phototheranostic agent for high-performance type I photodynamic and photothermal synergistic cancer therapy.

An Exceptional Broad-Spectrum Nanobiocide for Multimodal and Synergistic Inactivation of Drug-Resistant Bacteria

BackgroundResistance to traditional treatments has spurred research into innovative therapeutic approaches for tumors. Among these innovative treatments, photothermal therapy (PTT) has gained increasing attention for its use of photothermal agents (PTAs) to convert light into heat for localized tumor ablation. However, PTT faces limitations due to heat shock protein 70 (HSP70)-mediated resistance in tumor cells. Combining PTT via indocyanine green (ICG) with siRNA HSP70 could reduce the thermal resistance of the tumor, thereby enhancing treatment efficacy. Albumin-based nanoparticles (NPs) can effectively deliver ICG and siRNA into tumor cells. When exposed to near-infrared (NIR) light, these nanoparticles trigger lysosomal escape and release, further enhancing gene silencing activity.MethodsThis study aimed to develop a biocompatible delivery system, HSA@ICG/siRNA NPs, for photothermal-enhanced tumor therapy. The nanoparticles were characterized for size, charge, surface functionalization, and photoconversion properties. In vitro antitumor efficacy was evaluated using MTT assay, calcein AM/PI staining, RT-PCR, and Western blot in 4T1 tumor cells. In vivo, we assessed photothermal effects, biodistribution, tumor inhibition, and biosafety following irradiation.ResultsCharacterization confirmed the successful synthesis of uniform, stable HSA@ICG/siRNA NPs with effective photothermal conversion properties. Cellular uptake studies revealed high siRNA internalization, with laser-induced lysosomal escape enhancing cytoplasmic delivery. In vitro, gene silencing reduced mRNA and protein levels by 82.8% and 65%, respectively. In vivo, local tumor temperature increased to 42°C within 3 minutes, indicating a mild but effective photothermal effect. Tumor inhibition rates were 50.00% ± 9.16% for HSA@ICG and 71.26% ± 7.92% for HSA@ICG/siRNA, demonstrating enhanced tumor suppression. The treatment achieved sustained tumor targeting with minimal off-target toxicity.ConclusionAs a dual-function photothermal therapy agent, HSA@ICG/siRNA NPs combine targeted gene silencing with photothermal effects, demonstrating significant therapeutic promise. This integrated approach addresses tumor resistance, offering a potential advancement in cancer treatment strategies.

Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy

In this study, we introduce a novel nanoplatform, polypyrrole (PPy)‐2,2′‐Azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH)@lauric acid (LA) (PPy‐AIPH@LA) nanoparticles (NPs), designed to overcome these limitations through synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). This dual‐responsive system incorporates PPy for efficient photothermal conversion, AIPH for thermos‐responsive and oxygen‐independent free radical generation, and LA as a thermally responsive encapsulation layer. The LA coating melts upon 808 nm near‐infrared laser irradiation, releasing AIPH and free radicals to enable precise spatiotemporal activation of therapeutic effects. PPy‐AIPH@LA demonstrates exceptional photothermal conversion efficiency (55.74%) and generates sufficient radicals to enhance PDT efficacy, even in hypoxic tumor microenvironments. In vitro studies revealed concentration‐dependent tumor cell ablation and inhibition of migration, while in vivo experiments showed that the combined PTT‐PDT treatment achieved an impressive 90.7% tumor growth inhibition rate in a mouse colon cancer cells CT‐26 murine model, with no significant systemic toxicity. Molecular analyses further revealed modulations in pathways associated with tumor metabolism, apoptosis, and immune escape, highlighting the comprehensive therapeutic potential of this nanoplatform. These findings underscore the potential of PPy‐AIPH@LA as a safe, effective, and minimally invasive nanotherapeutic platform for combating CRC and other solid tumors.

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWOx ternary oxide nanoparticles and modified their surface with RGD-PEG-NH2 (FeWOx-PEG-RGD NPs), whereby resulting NPs possessed a (T2/T1) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWOx-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. In an acidic tumor microenvironment (TME) with a high hydrogen peroxide (H2O2) expression, NPs degraded to release Fe3+ and Fe2+, triggering a Fenton reaction to generate ˙OH for CDT. The released Fe2+ led to T2/T1 signal conversion for tracing cancer therapy, while the high X-ray attenuation coefficient of W also made it a good CT contrast agent for guided therapy. Thus, the structurally simple FeWOx-PEG-RGD was capable of mediating (T2/T1-weighted) MR/CT two modal imaging-guided PTT/PDT/CDT synergic therapy with a high accuracy and superb anticancer efficiency. The simple, degradable, rapid-clearance, and multifunctional FeWOx-PEG-RGD NPs provide a novel, promising, and versatile nanotheranostic platform.

Drug‐resistant biofilm infections pose a critical global health challenge, demanding innovative therapies. We developed a butterfly‐shaped aggregation‐induced emission luminogen (AIEgen), 4TPE‐DTB, as a potent photothermal agent for biofilm eradication. Encapsulating 4TPE‐DTB into pH‐responsive Cu 2 + ‐tannic acid nanoparticles (CTNPs) yielded a synergistic platform (DTB@CTNPs) combining mild photothermal therapy (PTT) with controlled Cu 2 + release. DTB@CTNPs exhibited strong bacterial membrane adhesion and acid‐triggered Cu 2 + release, specifically targeting biofilm microenvironments. 4TPE‐DTB enabled NIR‐II imaging‐guided therapy, permitting real‐time infection localization while generating localized hyperthermia under 808 nm irradiation. The photothermal effect disrupted bacterial membranes, enhancing intracellular Cu 2 + influx and antibacterial efficacy. In vitro, DTB@CTNPs eradicated mature biofilms at low doses. In vivo, they effectively treated methicillin‐resistant Staphylococcus aureus (MRSA) abscesses and Pseudomonas aeruginosa keratitis, demonstrating superior antibiofilm performance. This work presents a multifunctional nanoplatform synergizing AIEgen‐mediated mild PTT and Cu 2 + delivery, achieving potent bactericidal activity with minimal cytotoxicity. The strategy addresses a pressing unmet need in combating drug‐resistant biofilm infections.

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.

Photothermal therapy is an antibacterial strategy based on the photothermal conversion effect, characterized by rapid action and a low tendency for resistance. However, traditional photothermal materials often lack the ability to specifically target bacteria, which limits their precise bactericidal efficacy in complex infection environments. A nanoplatform integrating photothermal therapy and targeted antibacterial action, composed of the targeting fragment 4-carboxyphenylboronic acid, photothermal agent Ag2S, and stabilizer phycocyanin (PBA-Ag2S@PC NPs), has been successfully established. The experimental results indicate that PBA-Ag2S@PC NPs exhibit exceptional photothermal conversion capabilities and demonstrate targeted antibacterial effects, enhanced by photothermal action, against Staphylococcus aureus and Escherichia coli. Both in vitro and in vivo tests confirm the excellent biocompatibility of PBA-Ag2S@PC NPs and their potential to promote wound healing. Overall, the constructed PBA-Ag2S@PC NPs represent an efficient targeted photothermal antibacterial nanoplatform, demonstrating significant potential for promoting the repair of infected wounds.

Multidrug-resistant (MDR) bacteria are rapidly emerging, coupled with the failure of current antibiotic therapy; thus, new alternatives for effectively treating infections caused by MDR bacteria are required. Hyperthermia-mediated photothermal therapy (PTT) and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT) have attracted extensive attention as antibacterial therapies owing to advantages such as low invasiveness, low toxicity, and low likelihood of causing bacterial resistance. However, both strategies have notable drawbacks, including the high temperature requirements of PTT and the weak ability of PDT-derived ROS to penetrate target cells. To overcome these limitations, a combination of PTT and PDT has been used against MDR bacteria. In this review, we discuss the unique benefits and limitations of PTT and PDT against MDR bacteria. The mechanisms underlying the synergistic effects of the PTT-PDT combination are also discussed. Furthermore, we introduced advancements in antibacterial methods using nano-based PTT and PDT agents to treat infections caused by MDR bacteria. Finally, we highlight the existing challenges and future perspectives of synergistic PTT-PDT combination therapy against infections caused by MDR bacteria. We believe that this review will encourage synergistic PTT- and PDT-based antibacterial research and can be referenced for future clinical applications.

In this study, mesoporous silica nanoparticles (MSNs) have been successfully capped with graphene quantum dots (GQDs) to form multifunctional GQD-MSNs with the potential for synergistic chemo-photothermal therapy. The structure, drug-release behavior, photothermal effect, and synergistic therapeutic efficiency of GQD-MSNs to 4T1 breast cancer cells were investigated. The results showed that GQD-MSNs were monodisperse and had a particle size of 50-60 nm. Using doxorubicin hydrochloride (DOX) as a model drug, the DOX-loaded GQD-MSNs (DOX-GQD-MSNs) not only exhibited pH- and temperature-responsive drug-release behavior, but using near-infrared irradiation, they efficiently generated heat to kill cancer cells. Furthermore, GQD-MSNs were biocompatible and were internalized by 4T1 cells. Compared with chemotherapy and photothermal therapy alone, DOX-GQD-MSNs were much more effective in killing the 4T1 cells owing to a synergistic chemo-photothermal effect. Therefore, GQD-MSNs may have promising applications in cancer therapy.

Increasing number of resistant bacteria have emerged with the overuse of antibiotics, which indicates that the bacterial infection has become a global challenge. Furthermore, the pollution of antibiotics to the environment has become a serious threat to public health. It is known that toxins produced by bacteria are the main cause of bacterial infections. Photothermal therapy is an effective antibacterial approach. However, the photothermal reagents cannot eliminate bacterial toxins, and even some anti-bacterial materials are toxic. Here, we synthesized a biomimetic recycled nanoparticle, red blood cell (RBC) membrane-coated Fe3O4 nanoparticles (RBC@Fe3O4), as an antibacterial agent. The RBC@Fe3O4 nanoparticles act as nano-sponges to trap toxins and then kill them all with a photothermal effect. We can describe this process simply as a battle between two armies. Our strategy is to disarm the "enemy" so that we can easily kill the "enemy" who has no power, which results in enhancing the bactericidal efficacy. The toxin of methicillin-resistant Staphylococcus aureus (MRSA) was absorbed by RBC@Fe3O4in vitro. In addition, in vivo studies proved that the RBC@Fe3O4 nanoparticles confer obvious survival benefits against toxin-induced lethality by absorbing the toxin of MRSA. Furthermore, using a mouse model of MRSA wound infection, the RBC@Fe3O4 nanoparticles with laser irradiation were found to have a superior wound-healing effect. Simultaneously, the RBC@Fe3O4 nanoparticles could be recycled in a simple way without affecting the bactericidal efficacy. The highly biocompatible and recyclable RBC@Fe3O4 biomimetic nanoparticles based on photothermal therapy and bacterial toxin adsorption strategy are promising for treating bacterial infections.

Oral biofilms are associated with various oral diseases causing pain and discomfort, and pose a severe threat to general health. Conventional surgical debridement and antibacterial therapy often yield unsatisfactory outcomes because they either fail to fully and painlessly eliminate biofilms or increase the risk of bacterial resistance. In this study, we synthesized polydopamine-embellished Zn-MOFs (ZIF-8@PDA NPs), which can degrade under mildly acidic conditions to release Zn2+. These nanoparticles also convert near-infrared light energy into heat, thereby enabling synergistic photothermal and antibacterial metal ion therapy for oral biofilm eradication. Our findings reveal that therapy with ZIF-8@PDA NPs, when exposed to near-infrared radiation, demonstrates exceptional antibacterial efficacy and is highly effective in eradicating oral biofilms both in vitro and ex vivo. Furthermore, we used an in vivo rodent tooth biofilm model to demonstrate the suppression of dental caries. This work presents a promising solution for preventing and suppressing dental caries as well as other treating diseases linked to oral biofilm infections.

Organic small molecular nanoparticles based on self-assembly of amphiphilic fluoroporphyrins for photodynamic and photothermal synergistic cancer therapy