Low-temperature Photothermal Therapy Research Articles

A triple-mode strategy combining low-temperature photothermal, photodynamic, and chemodynamic therapies for treating infectious skin wounds.

The skin is the first natural barrier of the human body. Bacterial infections severely hinder the healing process of skin wounds and pose a great threat to human health. Therefore, it is particularly urgent to develop new antimicrobial strategies for bacterial pathogen clearance and wound healing. In this study, a metal-organic framework (MOF), Fe-MIL88B-NH2, was incorporated with the photosensitizer indocyanine green (ICG) to construct composite nanoparticles (MOF@ICG NPs) with multiple antibacterial activities. Under mild near-infrared (NIR) irradiation, the photosensitizer ICG in the MOF@ICG NPs undergoes photothermal conversion (∼45 °C) and photodynamic reactions to generate heat and singlet oxygen (1O2). In addition, the Fenton reaction of the NPs with hydrogen peroxide (H2O2) in the bacterial infection microenvironment resulted in the generation of hydroxyl radicals (˙OH), thus achieving the three-mode combination of low-temperature photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT). The in vitro experimental results showed that MOF@ICG MPs had excellent antibacterial properties and good cytocompatibility, with some ability to promote the migration of L-929 fibroblasts. Furthermore, under NIR irradiation, MOF@ICG NPs could significantly kill bacteria and promote skin wound healing according to the results of animal experiments. The wound healing rate reached 87.1% after 7 days of treatment. The research results break through the limitations of single-mode antibacterial technology and provide certain theoretical guidance and technical support for the research and development of new antibacterial materials.

Injectable Therapeutic Hydrogel with H2O2 Self-Supplying and GSH Consumption for Synergistic Chemodynamic/Low-Temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

A New Nanoplatform Under NIR Released ROS Enhanced Photodynamic Therapy and Low Temperature Photothermal Therapy for Antibacterial and Wound Repair.

Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA). In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect. Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.

A BRD4-Targeting Photothermal Agent for Controlled Protein Degradation.

BRD4 protein plays a pivotal role in cell cycle regulation and differentiation. Disrupting the activity of BRD4 has emerged as a promising strategy for inhibiting the growth and proliferation of cancer cells. Herein, we introduced a BRD4-targeting photothermal agent for controlled protein degradation, aiming to enhance low-temperature photothermal therapy (PTT) for cancer treatment. By incorporating a BRD4 protein inhibitor into a cyanine dye scaffold, the photothermal agent specifically bond to the bromodomain of BRD4. Upon low power density laser irradiation, the agent induced protein degradation, directly destroying the BRD4 structure and inhibiting its transcriptional regulatory function. This strategy not only prolonged the retention time of the photothermal agent in cancer cells but also confined the targeted protein degradation process solely to the tumor tissue, minimizing side effects on normal tissues through the aid of exogenous signals. This work established a simple and feasible platform for future PTT agent design in clinical cancer treatment.

Near-Infrared Light-Triggered NO Nanogenerator for Gas-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy to Eliminate Biofilms.

Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.

Biofilm ablation on titanium alloy surface by photothermal and chemotherapeutic synergistic therapy

With prolonged exposure in the human body, titanium alloy implants face challenges associated with bacterial attachment and proliferation, leading to implant failure and severe complications. Photothermal therapy (PTT) emerges as an efficient strategy for biofilm elimination. However, the local high temperature of PTT and incomplete bacteria ablation in low-temperature PTT pose risks of damage to normal tissues and biofilm recalcitrance, respectively. In this study, we synergistically combined photothermal therapy and chemotherapy to mildly disrupt biofilms of Staphylococcus aureus (S. aureus) to enhance the efficiency of biofilm ablation. The synergistic nanoplatform comprises near-infrared-light responsive conjugated polymers, heat-sensitive liposomes, and the antibiotic daptomycin for biofilm elimination. The heat generated by conjugated polymers, stimulated with 808 nm light, alters biofilm permeability and releases antibiotics locally to eradicate biofilm. The nanoparticles exhibit biofilm dispersion activity and can effectively inhibit biofilm growth for up to 5 days. Consequently, this nanoplatform based on conjugated polymers offers a reliable method for ablating biofilms on titanium alloy implant and exhibits potential in drug-resistant clinical applications.

Ti3C2Tx MXene nanosheet-based drug delivery/cascaded enzyme system for combination cancer therapy and anti-inflammation

Photothermal therapy (PTT)-based combination therapy is an effective approach to cancer treatment. However, there is a possibility of tumor development due to the inflammation caused by PTT. In addition, hyperthermia can cause damage to normal tissues. This work reported a drug delivery/cascade enzyme system based on Ti3C2Tx MXene nanosheets. Ultra-small, degradable mesoporous silica nanoparticles (DS-MSN) were prepared to load phloretin (Phl), which has anti-inflammatory, antioxidant, and anticancer properties. Subsequently, glucose oxidase (GOx) was adsorbed on the surface of DS-MSN. The nanoparticles were then modified on Ti3C2Tx MXene nanosheets and finally treated with polyethylene glycol (PEG) to obtain the multifunctional system named Ti3C2Tx-Phl@DS-MSN-GOx-PEG (TPDMGP). The high near-infrared photothermal conversion efficiency of Ti3C2Tx made it suitable for PTT. GOx and Ti3C2Tx formed a cascade enzyme system inside cancer cells: Ti3C2Tx exhibited catalase (CAT)-like activity that decomposed intracellular hydrogen peroxide (H2O2) into O2, which was provided to GOx for enhanced starvation therapy. GOx in the presence of O2 produces H2O2, for the oxygen production of Ti3C2Tx. Meanwhile, DS-MSN could be degraded in the reducing environment inside cancer cells as it contains disulfide bonds in its backbone, thus releasing Phl for chemotherapy. Such a combination therapy strategy could achieve a satisfactory therapeutic outcome by low-temperature PTT while evading normal tissue damage by high temperature. The anti-inflammatory effects of both Ti3C2Tx and Phl enabled TPDMGP to eliminate the inflammation caused by PTT via the scavenging of reactive oxygen species (ROS). The multifunctional system is expected to generate new paradigms for cancer PTT.

Self-floating and long-term stable Ti3C2TX/polyurethane composite membranes with highly efficient photothermal conversion performances for multiple applications

Photothermal conversion has emerged as a highly effective method for converting solar energy into thermal energy for a variety of applications. In this study, we developed Ti3C2TX/PU membranes with exceptional photothermal conversion performance using a simple casting process. The Ti3C2TX/PU membranes are flexible, self-floating, and possess suitable strength and hydrophilicity. Additionally, they exhibit enhanced sunlight absorption capability and excellent thermal stability. When these membranes were applied for solar-driven seawater evaporation, they achieved an evaporation rate of 1.35 kg∙m−2 h−1 and a conversion efficiency of 84.85 % under 1 sun. In real outdoor conditions, they also displayed satisfactory evaporation performance. Impressively, the Ti3C2TX/PU membranes exhibited stable salt resistance and remarkable self-desalting properties, which are crucial for practical seawater evaporation applications. Furthermore, we observed that the photothermal performance of the Ti3C2TX/PU membranes improved with a higher Ti3C2TX content. Particularly noteworthy is the significant reduction in ice melting time when these membranes are wrapped around power wires, demonstrating their excellent photothermal deicing capabilities. The Ti3C2TX/PU membranes also showed promising application potential in low-temperature photothermal therapy treatment. We believe that such efficient and stable photothermal membranes will provide a sustainable solution for addressing challenges related to human health, life, and survival.

Engineering of phytic acid-coated Prussian nanoparticles for combined Nitric oxide and Low-Temperature photothermal therapy of osteosarcoma

The overall survival rate for osteosarcoma (OS) has not shown any improvement over the past three decades, highlighting the persistent challenge in diagnosing and treating this disease. Nitric oxide (NO) plays a crucial role in some forms of tumor therapy. However, achieving precise and targeted release of NO remains an obstacle in anti-tumor treatment. Given this circumstance, the utilization of near infrared (NIR) laser-induced photothermal effect offers promising potential for controlled delivery of NO. In this study, we have successfully developed a therapeutic nanoparticle, PB@SNP-PA, by loading NO donor sodium nitroprusside (SNP) into Prussian blue (PB) and coating it with phytic acid (PA) for bone targeting, achieving controlled release of NO and enhancing the anti-tumor effect under NIR laser. Moreover, PB@SNP-PA significantly impairs the mitochondria of OS cells, alleviate heat tolerance induced by heat shock proteins, and mediate apoptosis as a potential anticancer mechanism. By utilizing the bisphosphonate-adsorption property of phytic acid, we have achieved bone targeting for PB@SNP-PA, which exhibits significant intra-tumoral enrichment and remarkable anti-tumor effects in vivo by inhibiting bone dissolution. These findings suggest that PB@SNP-PA functions as a unique platform for controlled NO release, proposing a novel approach for combined anti-tumor therapy involving photothermal and gas therapies.

Camptothecin-loaded and IR780-doped polydopamine nanomedicine used for multifunctional chemo-photothermal-photodynamic therapy for lung cancer

Lung cancer poses a major threat to human health. Camptothecin (CPT), a cytotoxic alkaloid derived from pyrroloquinoline, ranks alongside paclitaxel as the most widely studied natural broad-spectrum antitumor drug. However, poor water solubility and instability of the lactone ring hinder its clinical application. To improve the efficacy of CPT in lung cancer, we developed a polydopamine (PDA) nanoparticle formulation combined with photothermal therapy (PTT). Although PDA nanocrystals have good biocompatibility and excellent PTT conversion ability, their high-temperature PTT application tends to adversely affect normal tissues. By doping the surface of PDA nanoparticles with IR780, a near-infrared photosensitiser, a CPT-loaded PDA nanoparticle (CPT-PDA-IR780) was designed that was easy to modify and had strong adhesion. This formulation was used for lung cancer treatment. Due to the incorporation of a photosensitiser, CPT-PDA-IR780 nanomaterials showed better low temperature PTT properties and demonstrated significant anti-lung cancer effects both in vivo and in vitro. By combining chemotherapy and photodynamic therapy (PDT), this nanomedicine achieved better efficacy in low-temperature PTT for lung cancer. These findings provide a scientific basis for the development of CPT nanomaterials and for the treatment of lung cancer with low-temperature PTT through combination therapy.

Nitroreductase-responsive nanoparticles for in situ fluorescence imaging and synergistic antibacterial therapy of bacterial keratitis

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-xSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-xSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the Cu2-xSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.

Single NIR laser-activated synergistic low-temperature photothermal therapy and self-oxygenated photodynamic therapy nano-platforms for bacteria infection

The emergence and spread of drug-resistant bacterias with new resistance mechanisms leads to antimicrobial resistance and continues to threaten our ability to treat common infections. Herein, a nano-platform (PB@MnO2@MB@HA) was provided to bring significant bacterial inhibition via win-win photo-combination therapy strategy mediated by a single wavelength. More importantly, with well photothermal conversion efficiency, the nano-platform enables effective low temperature photothermal therapy (below 42 °C), where the heat generated is advantageous for the advancement of photodynamic therapy. Moreover, the addition of manganese dioxide promotes the supply of oxygen and addresses the limitations of low-oxygen environments on photodynamic therapy, further enhancing its therapeutic effect, which in turn compensates for the efficacy of low temperature photothermal. The nano-platform can effectively inhibit the growth of Gram-negative bacteria with an inhibition rate of 99%. In summary, the combined therapy of low-temperature photothermal therapy and self-oxygenated photodynamic therapy synergistically improves the efficacy of bacteria treatment while reducing the side effects associated with two therapy alone. The photo-combination nano-platform triggered by single wavelength near infrared irradiation has significant clinical application potential in overcoming the limitations of monotherapy for bacterial infection.

Mild low-temperature photothermal therapy demonstrated a distinctive 'hot spring' effect in the multichannel regulation of atherosclerosis instead of inducing foam cell apoptosis

Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.

Photothermal microneedle patch loaded with antimicrobial peptide/MnO2 hybrid nanoparticles for chronic wound healing

Chronic wound with complex clinical characteristics poses a significant challenge worldwide. Bioactive and stimulus responsive microneedle patch (MNP) has recently become one of the growing centers of wound healing, due to its suitability for suture-free tissue adhesion and transdermal cargo delivery. Herein, a series of double layer MNPs with dual antibacterial and reactive oxygen species (ROS)-scavenging abilities were firstly reported. Biocompatible methacrylated gelatin (GelMA) served as the base material of MNP. An artificial intelligence (AI)-derived antimicrobial peptide (AMP) was electrostatically assembled with hollow MnO2 nanoparticles, and then loaded onto microneedle tips. The products (named as GMCM) exhibited good photothermal conversion and anti-oxidative nanozyme activities. GMCM combined with low temperature photothermal therapy (LTPT) could not only relieve ROS-induced cell damage, but also inhibit the survival and proliferation of host bacteria. The broad-spectrum antibacterial activity of GMCM was solid, minimizing the potential of bacterial resistance. Wound healing evaluations were performed using a S. aureus infected skin defect model. The combination of GMCM and LTPT could complete the wound healing within 15 days, and the overall effect was better than that of product control (3 M®). In conclusion, this work will provide a competitive biomaterial for accelerating chronic wound healing.

Low-temperature photothermal-chemotherapy enhancing tumor immunotherapy by tetrahedral framework nucleic acids nanogels based drug delivery system

To achieve a balance between antitumor efficacy in photothermal therapy (PTT) and high-temperature (>50℃) induced side effects, a novel tetrahedral framework nucleic acid (FNA) nanogel (FNANG) coated with polydopamine (PDA) (abbreviation: PP-FNANG) was designed to achieve siRNA-mediated low-temperature PTT. First, siRNA targeted heat shock protein 70 (HSP70) was used as crosslinker to guide FNA through nucleic acid hybridization to obtain FNANG, and simultaneously loaded doxorubicin (DOX). The obtained FNANG was coated with PEGylated PDA, which not only protected the FNANG from enzymatic degradation, but also made the FNANG have excellent photothermal conversion ability under near infrared (NIR) irradiation. FNANG realized the effective delivery of siHSP70 and realized the low-temperature photothermal therapy mediated by siRNA. Notably, PP-FNANG combined with its loaded DOX showed excellent synergistic effect, and could effectively induce the immunogenic cell death (ICD), promote the activation and infiltration of T lymphocyte, promote the maturation of dendritic cells and the secretion of related cytokines, and effectively inhibit melanoma. This study provided a simple and effective exploration strategy for new vector design based on FNA and collaborative therapy.

Manganese Dioxide/Gold-based Active Tumor Targeting Nanoprobes for Enhancing Photodynamic and Low-Temperature-Photothermal Combination Therapy in Lung Cancer.

Tumor drug resistance caused by the tumor microenvironment is an extremely difficult problem for researchers to solve. Nanoplatforms that integrate diagnosis and treatment have great advantages in tumor treatment, but the design and synthesis of simple and efficient nanoplatforms still face tremendous challenges. In this study, a novel Mn/Au@ir820/GA-CD133 nanoprobe was developed. The manganese dioxide/gold particles were prepared by coprecipitation/assembly, chemically coupled with CD133 antibody, and finally loaded with the photosensitive drug IR820 and the heat shock protein inhibitor Ganetespib. The nanoprobe demonstrated good tumor-targeting ability, increased the level of singlet oxygen produced from laser irradiation by effectively alleviating tumor hypoxia, and decreased the threshold of heat tolerance by downregulating the expression of HSP90 in tumor tissues. This nanoprobe successfully inhibited the growth and progression of tumor tissues in a tumor-bearing mouse model by improving the effectiveness of photodynamic and low-temperature photothermal combination therapy.

Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

All-in-One Engineering Multifunctional Nanoplatforms for Sensitizing Tumor Low-Temperature Photothermal Therapy In Vivo.

Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS2 nanoparticles as the photothermal core to generate low temperature (40-48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe2+ and was further modified with PEG and iRGD to enhance tumor specificity (MoS2/Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H2O2 content, cooperate with Fe2+ ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.

Drug-Primed Self-Assembly of Platinum-Single-Atom Nanozyme to Regulate Cellular Redox Homeostasis Against Cancer.

Single-atom nanozymes (SAzymes) with high catalytic activity exhibit the potential to disequilibrate the reactive oxygen metabolic balance in the tumor microenvironment (TME), which contains several endogenous reductive substances such as glutathione (GSH). Herein, a novel nano-assembly (CDs@Pt SAs/NCs@DOX) is first constructed using drug-primed platinum (Pt) single-atom or nanocluster nanozymes with a Pt loading of 34.8%, which exhibits prominent dual enzymatic activities to mimic peroxidase (POD) and glutathione oxidase (GSHOx). The unique GSHOx-like activity can efficiently scavenge GSH with a relatively low Km (1.04mm) and high Vmax (7.46×10-6 ms-1 ), thus avoiding single oxygen (1 O2 ) depletion. CDs@Pt SAs/NCs@DOX simultaneously demonstrates low-temperature photothermal therapy and TME- or laser-controlled disassembly and drug release, which can effectively regulate cellular redox homeostasis and achieve high tumor growth inhibition. These outcomes may provide promising strategies for the preparation of Pt SAzymes with multiple activities and variable-sized nano-assemblies, allowing for broader applications of SAzymes and nano-assemblies in the biomedical field.

NIR laser-activated multifunctional nanocomposites for cascade low-temperature photothermal and oxygen-irrelevant thermodynamic therapy

Osteosarcoma, occurring most frequently in adolescents, are highly malignant bone tumor and prone to develop local recurrence and long-distance metastasis. Therefore, new comprehensive therapeutic strategies for osteosarcoma are urgently needed. Different from traditional photothermal therapy (PTT), low temperature PTT (LTPTT) not only brings less heat damages to the surrounding normal tissues but also prevent tumor metastasis. Nevertheless, its therapeutic effects are severely attenuated due to the tumor thermo-resistance induced by the overexpression of heat shock protein (HSP). In our work, an acid-responsive core–shell nanocomposite was fabricated for cancer therapy. The nanoplatform can independently encapsulate alkyl radical initiator 2,2-azobis[2-(2-imidazolin-2-yl) propane]-dihydroch-loride (AIPH) in the mesoporous polydopamine (MPDA) core and HSP inhibitor (gambogic acid, GA) in the zeolite imidazolate framework-8 (ZIF-8) microporous shell, called MPDA/AIPH@ZIF-8/GA (MAZG), which could achieve the combined functions of LTPTT and thermodynamic therapy (TDT). After endocytosing by tumor cells, the pH-responsive degradation of the ZIF-8 coating stimulates the rapid release of GA, which can effectively inhibit HSP expression in advance, and then simultaneously enhanced the therapeutic efficacy of LTPTT. Further, both in vitro and in vivo experiments have demonstrated that the as-synthesized MAZG nanocomposite exhibited favorable biosafety and remarkable tumor growth inhibition.