Near-infrared Laser Irradiation Research Articles

Combination of gold nanoparticles with near-infrared light as an alternative approach for melanoma management.

Melanoma is the most aggressive type of skin cancer and recently approved drugs are often associated with resistance and significant adverse effects. Therefore, the design of more effective and safe options remains imperative. Photothermal therapy (PTT) using gold nanoparticles (AuNPs) presents a promising and innovative approach. In this work, the efficacy of combining a previously optimized formulation of AuNPs coated with a mixture of hyaluronic and oleic acids (HAOA-AuNPs) with near-infrared (NIR) laser irradiation in melanoma cell lines was explored. Coated and uncoated AuNPs formulations were characterized in physicochemical, morphological and elemental terms. Next, the cellular uptake efficiency as well as antiproliferative activity of the combination of each formulation with laser irradiation was evaluated. Subsequently, HAOA-AuNPs were selected to assess the underlying mechanism of combined therapy by cell cycle and Annexin V/PI assays. An in vivo syngeneic murine melanoma model was also conducted. In vitro studies demonstrated that 24 h after incubation and in the absence of laser, HAOA-AuNPs did not exhibit cytotoxic effects on the melanoma cell lines tested, similar to the laser alone. On the contrary, the combination therapy resulted in a large reduction in cell viability. Furthermore, it has been shown to promote S-phase cell cycle arrest and increase in the percentage of late apoptotic cells. Finally, the in vivo proof-of-concept showed that the intratumoral administration of HAOA-AuNPs followed by three laser irradiations impaired tumor progression. Collectively, AuNP-based PTT holds significant potential to improve treatment efficacy and safety, offering a versatile and potent tool against cancer.

Engineering PSMA-targeted nanoparticles co-encapsulating mitoxantrone and indocyanine green for precise combinatory therapy in prostate cancer

Prostate cancer is the 2nd most common cancer in men worldwide. Chemotherapeutic treatment of prostate cancer with mitoxantrone (MTX) has limited efficacy due to severe side effects in which cardiotoxicity and myelosuppression are the two major causes of its dose-limiting toxicity. This study aimed to obtain a poly (lactic-co-glycolic acid) (PLGA) nanoparticle that can precisely deliver MTX to the prostate cancer cells overexpressing the Prostate-specific membrane antigen (PSMA) receptor-sparing healthy tissues and co-loading Indocyanine green (ICG) as a fluorescent photothermal/photodynamic agent for precise combinatory therapy in prostate cancer. The biocompatible polymer PLGA was covalently modified with the peptide of sequence (WQPDTAHHWATL) to actively target the PSMA receptor. Factors like the peptide-to-polymer ratio or the peptide's orientation during the polymer's chemical modification were investigated to enhance the active targeting of the nanoparticles (NPs). NPs were characterised using dynamic light scattering, scanning electron microscopy, and UV–vis spectroscopy to determine their morphological and colloidal properties and optimal MTX and ICG encapsulation efficiency. Quantitative FACS analysis of LNCaP and PC-3 cells incubated with Nile Red-labelled non-targeted PLGA or PLGA-PSMA targeted NPs was assessed to identify the best formulation that bound selectively to PSMA. The orientation of the peptide conjugated to the polymer, which has the C-terminal end of the peptide sequence accessible for interaction with the cell receptor, maximises the targeting capacity of the system. Photothermal experiments using 808 nm near-infrared laser irradiation were conducted, and cytotoxicity was assessed using the resazurin viability assay. Remarkably, our results confirmed the safety and efficacy of a targeted and activatable therapy using polymeric NPs functionalised with the peptide and co-loaded with MTX and ICG. This pioneer nanosystem opens new perspectives for exploring advanced targeted delivery in prostate cancer. It offers a straightforward methodology for functionalising drug delivery systems with bioactive peptides that can be applied to different types of cancer.

A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS2-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size containing molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation, the nanosheets heat up to ≥50 °C leading to polymer softening and release of the drug. MoS2 nanosheets exhibit high photothermal conversion efficiency and require low-power laser irradiation. A machine learning algorithm was applied to acquire the optimal laser operation conditions. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered, and after 3-cycle laser treatment, the system conferred synergistic phototherapeutic and chemotherapeutic effects. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 39 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system is therapeutically relevant for patients in need of recurring cycles of treatment on small tumors, since it provides precise localization and low invasiveness and is not cross-resistant with other treatments.

Multifunctional nanoplatform with near-infrared triggered nitric-oxide release for enhanced tumor ferroptosis

Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment.Graphical abstract

Biodegradable ICG-Conjugated Germanium Nanoparticles for In Vivo Near-Infrared Dual-Modality Imaging and Photothermal Therapy.

Theranostics, by integrating diagnosis and therapy on a single platform, enables real-time monitoring of tumors during treatment. To improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic imaging modalities can complement each other to achieve high resolution and a deep penetration depth. Despite the superior performance, the biodegradability of theranostic agents plays a critical role in enhancing nanoparticle excretion and reducing chronic toxicity, which is essential for clinical applications. Herein, we synthesize biocompatible and biodegradable indocyanine green (ICG)-conjugated germanium nanoparticles (GeNPs) and investigate their biodistributions in nude mice and 4T1 tumor models after intravenous injections using near-infrared (NIR) dual-modality fluorescence and photoacoustic imaging. The ICG-conjugated GeNPs have strong NIR absorption due to the NIR-absorbing ICG and Ge in combination, emit strong NIR fluorescence due to the multilayered ICG coatings, and exhibit very low in vitro and in vivo toxicity. After tail vein injections, the ICG-conjugated GeNPs mainly accumulate in the liver and spleen as well as the tumor with the help of the enhanced permeability and retention effect. The tumor's fluorescence signal is much stronger than that of the control group injected with pure ICG solution, as the GeNPs can function as biodegradable carriers for efficiently delivering the ICG molecules to the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the tumor can also be utilized for photothermal treatment under NIR laser irradiation, after which the tumor volume almost diminishes after 14 days. The experimental findings in this work demonstrate that the ICG-conjugated GeNPs are promising theranostic agents with exceptional biodegradability for in vivo NIR dual-modality imaging and photothermal therapy.

Copper Sulfide Nanorod-Embedded Urinary Catheter with Hydrophobicity and Photothermal Sterilization.

The high prevalence of catheter-associated urinary tract infections (CAUTIs) is causing significant concern in healthcare systems. Antibacterial urinary catheters have been developed to prevent CAUTIs in clinical application. In this work, a copper sulfide nanorod (CuS NR)-embedded urinary catheter (CuS/UC) was designed as an antibacterial urinary catheter with photothermal sterilization. The CuS NRs with low cytotoxicity were synthesized via the hydrothermal method. The CuS NRs were embedded into urinary catheters at different weight percentages. The CuS/UC exhibited homogenous surface roughness, low wettability, hydrophobicity, and low adhesiveness, promoting minimal interaction with bacteria and healthy cells. Under near-infrared (NIR) laser irradiation, the 0.8 weight percentage of CuS NRs in the urinary catheter (0.8CuS/UC) reached a temperature of 67.4 °C, demonstrating its photothermal antibacterial activity and suitability for catheter sterilization. Agar plate test verified that CuS/UCs exhibited a superior photothermal antibacterial activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Streptococcus aureus (S. aureus). Moreover, the 0.8CuS/UC exhibited excellent biocompatibility and anti-cell adhesion properties. The 0.8CuS/UC with photothermal performance, excellent biocompatibility, and anti-cell adhesion properties demonstrated its potential as a photothermal antibacterial catheter for clinical applications.

Photothermally enhanced antibacterial wound healing using albumin-loaded tanshinone IIA and IR780 nanoparticles.

Chronic and infected wounds, particularly those caused by bacterial infections, present significant challenges in medical treatment. This study aimed to develop a novel nanoparticle formulation to enhance wound healing by combining antimicrobial and photothermal therapy using albumin as a carrier for Tanshinone IIA and the near-infrared photothermal agent IR780. The nanoparticles were synthesized to exploit the antimicrobial effects of Tanshinone IIA and the photothermal properties of IR780 when exposed to near-infrared laser irradiation. Characterization of the nanoparticles was performed using Transmission Electron Microscopy (TEM) and spectroscopic analysis to confirm their successful synthesis. In vitro antibacterial activity was evaluated using cultures of methicillin-resistant Staphylococcus aureus (MRSA), and in vivo efficacy was tested in a mouse model of MRSA-infected wounds. Wound healing progression was assessed over 16days, with statistical analysis performed using two-way ANOVA followed by Tukey's post-hoc test. The nanoparticles demonstrated significant photothermal properties, enhancing bacterial eradication and promoting the controlled release of Tanshinone IIA. In vitro studies showed superior antibacterial activity, especially under photothermal activation, leading to a substantial reduction in bacterial viability in MRSA cultures. In vivo, nanoparticle treatment combined with near-infrared laser irradiation significantly improved wound closure rates compared to controls and treatments without photothermal activation. By the 16th day post-treatment, significant improvements in wound healing were observed, highlighting the potential of the combined photothermal and pharmacological approach. These findings suggest that albumin-loaded nanoparticles containing Tanshinone IIA and IR780, activated by near-infrared light, could offer an effective therapeutic strategy for managing chronic and infected wounds, promoting both infection control and tissue repair.

Multifunctional hyaluronic acid ligand-assisted construction of CD44- and mitochondria-targeted self-assembled upconversion nanoparticles for enhanced photodynamic therapy.

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core-shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments.

Radical-Scavenging Violet Phosphorus Nanosheets for Attenuating Hyperinflammation and Promoting Infected Wound Healing.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7nm VPNSs arefabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications.

Salmonella Biomimetic Nanoparticles for Photothermal-Chemotherapy of Colorectal Cancer.

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella, we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

Hollow Copper Sulfide Nanocubes Loaded with Pt(IV) Complexes for Cancer Multimodal Therapy.

Chemotherapy (CT) can significantly inhibit tumor growth, metastasis, and recurrence during cancer therapy. People have widely used platinum drugs in cancer treatment. However, as most chemotherapeutic drugs, platinum drugs still have shortcomings such as poor solubility, low cell uptake, nonspecific distribution, multidrug resistance, and adverse side effects. Therefore, we synthesized hollow copper sulfide (CuS) nanocubes with photothermal and photodynamic properties as carriers for Pt(IV) drugs. Hollow CuS nanocubes have attracted considerable interest in the field of cancer photothermal therapy (PTT) using multiple biological windows. Under near-infrared (NIR) laser irradiation, Cu2+ can be reduced into Cu+ in the presence of hydrogen peroxide in the tumor microenvironment. The resulting Cu+ can be used for photodynamic therapy (PDT), which can perform a Fenton-like reaction under acidic conditions (pH 5.5-6.5) and catalyze hydrogen peroxide to produce ·OH in the tumor microenvironment. In addition, compared with Pt(II) drugs, Pt(IV) drugs not only have lower systemic toxicity but also consume glutathione (GSH), thereby increasing reactive oxygen species (ROS) levels in tumor cells and effectively promoting PDT. In this study, we oxidized ethylenediamine platinum chloride to its tetravalent state, loaded the Pt(IV) complexes using hollow CuS nanocubes, and modified the surfaces of the nanoparticles with PEG to improve the EPR effect. The Pt(IV)-loaded hollow CuS nanocubes modified with PEG (Pt(IV)-CuS@PEG) are expected to be used for tumor chemo/photothermal/photodynamic therapy.

Construction of Methotrexate-Loaded Bi2S3 Coated with Fe/Mn-Bimetallic Doped ZIF-8 Nanocomposites for Cancer Treatment Through the Synergistic Effects of Photothermal/Chemodynamic/Chemotherapy.

A combination of therapeutic modalities in a single nanostructure is crucial for a successful cancer treatment. Synergistic photothermal therapy (PTT) can enhance the effects of chemodynamic therapy (CDT) and chemotherapy, which could intensify the therapeutic efficacy to induce cancer cell apoptosis. In this study, Fe and Mn on a zeolitic imidazolate framework (ZIF-8) (Fe/Mn-ZIF-8; FMZ) were synthesized through ion deposition. Furthermore, bismuth sulfide nanorods (Bi2S3 NRs; BS NRs) were synthesized via a hydrothermal process and coated onto FMZ to generate the core-shell structure of the Bi2S3@FMZ nanoparticles (B@FMZ). Next, methotrexate (MTX) was loaded effectively onto the porous surface of ZIF-8 to form the B@FMZ/MTX nanoparticles. The Fenton-like reaction catalyzes Fe2+/Mn2+ ions by decomposing H2O2 in the tumor microenvironment, resulting in the formation of toxic hydroxyl radicals (·OH), which promotes the CDT effect of killing cancer cells. Furthermore, under 808 nm laser irradiation, these B@FMZ nanoparticles showed a strong PTT effect, owing to the presence of intense BS NRs as a photothermal agent. The B@FMZ nanoparticles exhibited a prominent drug release efficiency of 87.25% at pH 5.5 under near-infrared laser irradiation due to the PTT effect can promote the drug delivery performance. The B@FMZ nanoparticles were subjected to dual-modal imaging, guided magnetic resonance imaging, and X-ray computed tomography imaging. Both in vitro and in vivo results suggested that the B@FMZ/MTX nanoparticles exhibited enhanced antitumor effects through the combined therapeutic effects of PTT, CDT, and chemotherapy. Therefore, these nanoparticles exhibit good biocompatibility and are promising candidates for cancer treatment.

Autophagy activator-loaded bicomponent peptide nanocarriers for phototherapy-triggered immunity enhancement against metastatic breast cancer

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer.

NIR-Actuated Botanicals/Nanozymes Nanofibrous Membranes for Antibiotic-Free Triple-Synergistic Therapy Against Polymicrobial Wound Infections.

Polymicrobial wound infection represents a significant contributor to infectious disease-related morbidity and mortality globally. Traditionally, the management of such infection relies heavily on high doses of antibiotics, often resulting in systemic side effects and exacerbating antibiotic resistance. Consequently, there is an urgent need to develop a safe and effective platform for antibiotic-free treatment of polymicrobial wound infections. In this study, a near-infrared (NIR) light-actuated nanofibrous membrane incorporating botanicals and nanozymes is presented for antibiotic-free triple-synergistic therapy against polymicrobial wound infections. The membrane integrates berberine hydrochloride (BBH)-loaded hollow zinc-doped carbon nanocubes into polyvinyl alcohol (PVA) nanofibrous membranes. Upon low-intensity 808nm NIR laser irradiation (0.3Wcm-2), the membrane achieved a controlled release of BBH and enhanced peroxidase-like (POD-like) enzyme activity. This NIR light-actuated botanical/photothermal therapy (PTT)/chemodynamic therapy (CDT) system demonstrated high efficacy in eradicating methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa both in vitro and in vivo. Furthermore, it mitigated inflammation and promoted wound healing in polymicrobial infection wounds, highlighting its potential as a promising alternative to antibiotic-based therapies.

Double-camouflaged tellurium nanoparticles for enhanced photothermal immunotherapy of tumor

The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

NIR-Actuated Ferroptosis Nanomotor for Enhanced Tumor Penetration and Therapy.

Ferroptosis nano-inducers have drawn considerable attention in the treatment of malignant tumors. However, low intratumoral hydrogen peroxide level and complex biological barriers hinder the ability of nanomedicines to generate sufficient reactive oxygen species (ROS) and achieve tumor penetration. Here a near-infrared (NIR)-driven ROS self-supplying nanomotor is successfully designed for synergistic tumor chemodynamic therapy (CDT) and photothermal therapy (PTT). Janus nanomotor is created by the asymmetrical modification of polydopamine (PDA) with zinc peroxide (ZnO2) and subsequent ferrous ion (Fe2+) chelation via the polyphenol groups from the PDA, here refer as ZnO2@PDA-Fe (Z@P-F). ZnO2 is capable of slowly releasing hydrogen peroxide (H2O2) into an acidic tumor microenvironment (TME) providing sufficient ingredients for the Fenton reaction necessary for ferroptosis. Upon NIR laser irradiation, the loaded Fe2+ is released and a thermal gradient is simultaneously formed owing to the asymmetric PDA coating, thus endowing the nanomotor with self-thermophoresis based enhanced diffusion for subsequent lysosomal escape and tumor penetration. Therefore, the release of ferrous ions (Fe2+), self-supplied H2O2, and self-thermophoresis of nanomotors with NIR actuation further improve the synergistic CDT/PTT efficacy, showing great potential for active tumor therapy.

Photothermally reinforced chemodynamic therapy in the treatment of osteosarcoma by polydopamine-modified, copper peroxide loaded ZIF8 nanoparticles

Chemodynamic therapy (CDT) has played an important role in osteosarcoma (OS) treatment. However, the insufficient content of endogenous H2O2 and high expression of glutathione (GSH) in tumor tissues limit the antitumor efficacy of CDT. In this work, we developed polydopamine (PDA) coated and CuO2 NPs loaded ZIF8 nanoparticles (CuO2@ZIF8@PDA NPs) for thermally reinforced CDT treatment of OS. The CuO2@ZIF8@PDA NPs exhibited excellent stability in neutral solutions while degraded in weakly acidic environments to generate hydrogen peroxide (H2O2) and Cu2+. Cu2+ consumes GSH in tumor tissues to generate Cu+. Both Cu2+ and Cu+ catalyzed the decomposition of H2O2, triggering a Fenton-like reaction to produce hydroxyl radicals (•OH). The PDA coating endowed the nanosystem with photothermal conversion capabilities under near-infrared laser irradiation, further promoting the generation of •OH, and inducing tumor cell death. In vitro experiments demonstrated that CuO2@ZIF8@PDA NPs exhibited significant toxicity towards K7M2 cells while remaining non-toxic to normal cells. In vivo studies revealed that under 808 nm laser irradiation, CuO2@ZIF8@PDA NPs exhibited stronger killing ability against K7M2 cells than CuO2@ZIF8@PDA NPs alone. This system, which combines GSH depletion, intratumoral H2O2 self-generation, and photothermally enhanced CDT, holds great promise for playing a pivotal role in the treatment of osteosarcoma.

Engineering AIEgens-Tethered Gold Nanoparticles with Enzymatic Dual Self-Assembly for Amplified Cancer-Specific Phototheranostics.

Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.

Photothermal Properties of Solid-Supported Gold Nanorods.

Gold nanoparticles possess unique photothermal properties and have gained considerable interest in biomedical research, particularly for photothermal therapy (PTT). This study focuses on evaluating the photothermal properties of gold nanorods (AuNRs) supported on glass substrates upon excitation with near-infrared (NIR) light. Two aspect ratios of AuNRs were electrostatically immobilized onto glass with controlled coverage. In situ X-ray diffraction (XRD) was performed to evaluate the photothermal behavior and morphological changes of the supported AuNRs during NIR laser irradiation. The XRD data sets were corroborated with scanning electron microscopy and Vis-NIR spectroscopy characterization. XRD revealed a linear temperature increase with laser power, aligning with theoretical predictions, and a slope dependent on the AuNR coverage, until the onset of morphology transformations around 120 °C. This study provides valuable insights into the photothermal properties of supported AuNRs, crucial for their application in PTT.

Titanium Carbide-Based Spatiotemporally Selectable-Activated Entropy-Driven DNA Nanoplatform for Amplified MicroRNA Imaging and Photothermal Therapy In Vivo.

Engineering an elaborate nanotheranostic platform that can achieve spatiotemporally selective microRNA (miRNA) imaging and imaging-guided therapy in time is critical for precise cancer diagnosis and efficient treatment, yet remains a challenge. Herein, we present an on-site-activatable nanotheranostic platform (Ti3C2-NEDR) that engineers a photothermal-activated entropy-driven strand displacement reaction (NEDR) module on a photothermal conversion module (Ti3C2) for achieving spatiotemporally controlled miRNA-21 imaging in vivo and imaging-guided photothermal therapy only by varying the power of the near-infrared (NIR) laser. The upstream NIR photothermal conversion module, Ti3C2, can act not only as a DNA circuit carrier to deliver the NEDR module but also as a photothermal agent to activate the downstream NEDR module in low-power NIR laser irradiation. Once the NEDR module is activated by the NIR laser, the entropy-driven strand displacement reaction can be innated by intracellular miRNA-21 to generate an amplified fluorescence signal for the spatiotemporally selective imaging of miRNA-21 in vivo. Thereafter, the imaging-guided in vivo photothermal therapy can be achieved in time only by switching to the high-power NIR laser. It is envisioned that this strategy of NIR light-activated spatiotemporally selective miRNA imaging and imaging-guided on-demand therapy may expand the nanotheranostic platform for precise cancer diagnosis and personalized therapy in time, providing a remarkable prospect in biomedical diagnosis and therapy.