Photothermal Nanoagents Research Articles

Aggregation-Induced Emission-Active Organic Nanoagent with High Photothermal Conversion Efficiency for Near-Infrared Imaging-Guided Tumor Photothermal Therapy.

Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D-A-D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.

Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications

Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.

Promising two-dimensional rhenium diselenide nanosheets: Facile Preparation, characterization, in vivo tumor photoacoustic imaging and photothermal therapy

Nanoagent-mediated photothermal therapy (PTT) has been considered as an useful strategy for curing cancer. Nonetheless, identifying high-quality photothermal nanoagents with excellent biocompatibility testing, superior photothermal conversion efficiency (PTCE), and high treatment efficacy, is still a key dilemma for performing practical application in biomedicine field. In our work, a novel photothermal nanoagent named two-dimensional (2D) colloidal rhenium diselenide (ReSe2) nanosheets was exfoliated via a facile liqiud-assisted exfoliation approach. Owing to surface functionalization with poly-ethylene glycol (PEG), the obtained PEG-ReSe2 nanosheets demonstrated good solubility and excellent biocompatibility. Notably, the PEG-ReSe2 nanosheets showed excellent near infrared (NIR) photothermal activity. For the radiation of an NIR laser at 808 nm, an ultrahigh PTCE of 81.3% was demonstrated. Owing to its high Re element and good photoacoustic effect, the PEG-ReSe2 nanosheets can serve as good contrast nanoagents for in vivo photoacoustic (PA) imaging. Furthermore, the PEG-ReSe2 nanosheets acted as excellent photothermal agents (PTAs) for performing PTT. Thanks to high photothermal effects of PEG-ReSe2 nanosheets, in vitro photothermal effects showed that, the mortality rate of 4T1 cells was almost 100%. Meanwhile, in vivo experiments showed that mouse tumors were 100% ablated. More importantly, the PEG-ReSe2 nanosheets exhibited negligible levels of toxicity, as demonstrated by in vivo cytotoxicity assays and histological analysis. Finally, changes in micro-RNA expression level was proposed to assess PTT treatment efficacy of PEG-ReSe2 nanoagent. Interestingly, the miRNAs such as miR-125b-5p, miR-20a-5p, miR-214–3p, miR-221–3p, miR-212–3p and miR-27b-3p, were down-regulated. In addiiton, the miRNAs including miR-451a, miR200c-3p, and miR-let-7d-3p, were up-regulated. More importantly, these obtained miRNAs can work as typical indicators for screening PTT outcomes of PEG-ReSe2 nanosheets-involved PTT. Our research suggested that, the PEG-ReSe2 nanoagent may represent potential therapeutic nanoagents for in vivo photoacoustic imaging and cancer therapy.

Dual‐Active Center AgFeCu Nanocatalyst for Tumor Destruction via Self‐Catalytically Enhanced Mild Photothermal Therapy

AbstractMild photothermal therapy (mPTT) has emerged as a highly promising approach for tumor ablation. However, the heat‐induced overexpression of heat shock proteins (HSPs) limits its efficacy by increasing cellular temperature tolerance. Herein, a self‐catalytically enhanced mild PTT strategy that directly disrupts the structure of HSPs to restore tumor cell sensitivity is proposed. In the proof‐of‐concept study, AgFeCu nanoparticles (AgFeCu NPs) with dual‐active catalytic centers (Fe‐Cu) and near‐infrared photothermal properties are developed. The AgFeCu NPs can efficiently catalyze the conversion of endogenous hydrogen peroxide into hydroxyl radicals in situ, leading to the degradation of HSPs and enhancing the therapeutic effects of mild PTT mediated by their Ag‐based substrates. Furthermore, AgFeCu NPs can also induce oxidative stress by depleting intracellular glutathione and promoting lipid peroxidation, thereby triggering tumor ferroptosis and resulting in significant tumor elimination in a U87MG murine tumor model. This self‐catalytically enhanced strategy maximizes the efficacy of mild PTT while minimizing damage to healthy tissues, which is expected to provide valuable insights for the development of next‐generation photothermal nanoagents for improved tumor therapeutics.

Mo-based Mo2Ti2C3 MXene as photothermal nanoagents to eradicating methicillin-resistant Staphylococcus aureus with photothermal therapy

Over the last decades, two-dimensional (2D) materials have progressively yielded great outcomes sparking intense research owing to their unique configuration and physicochemical properties. Their current research has effectively been channeled for biomedical purposes. Among them is the largest family, 2D transitional metal carbides (MXenes). In this context, Mo2Ti2C3 (MTC) a form of MXenes with excellent photo-conversion capacity was fabricated and its rising popularity due to its potential for possible treatment of infectious diseases was probed. We demonstrated that MTC MXene's potentiality for the conversion of the photo to heat showed better efficacy in inhibiting the growth of methicillin-resistant Staphylococcus aureus (MRSA). MTC under laser treatment completely killed MRSA, a combined treatment that caused an irreversible antibacterial effect. Also, MTC impeded bacteria-associated infections by completely killing MRSA in an infected wound, preventing tissue proliferation, angiogenesis, and tissue inflammations, demonstrating good biocompatibility, a sure prospect for clinical translation. Furthermore, the collaborative work of the MTC and the local hyperthermia significantly ameliorated MRSA-induced subcutaneous infection and bacterial keratitis, preserving the structural wholeness and transparency of the infected cornea. This study suggests that MTC may serve as a potential platform to augment near-infrared (NIR) therapeutic eradication of bacteria actively and precisely.

Gas-Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy.

The metabolic reprogramming of tumors requires ATP to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature can help in tumor ablation, it frequently leads to severe side effects such as chronic inflammation and hyper-immunogenicity. Therefore, improving therapeutic responsiveness and promoting wound healing are crucial considerations in PTT development. In this context, we proposed a gas-mediated energy remodeling strategy to enhance the efficacy of mild PTT at moderate temperatures while minimizing side effects. In the proof-of-concept study, an FDA-approved drug-based hydrogen sulfide (H2S) donor was developed to provide a sustained supply of H2S to tumor sites, serving as an adjuvant to mild PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to overcome the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoplatforms.

Gas‐Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy

AbstractThe metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting healing are critical considerations in the development of PTT. Here, we proposed a gas‐mediated energy remodeling strategy to improve mild PTT efficacy while minimizing side effects. In the proof‐of‐concept study, a Food and Drug Administration (FDA)‐approved drug‐based hydrogen sulfide (H2S) donor was developed to provide a sustained supply of H2S to tumor sites, serving as an adjuvant to PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to be a universal solution for overcoming the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoagents.

Selenide Heterostructure Nanosheets with Efficient Near-Infrared Photothermal Conversion for Therapy.

Photothermal therapy has been regarded as one of promising ways for tumor treatment. However, nanoagents with highly efficient thermal conversion and good bio-compatibility are still needed to be developed in biomedicine. In this work, we prepared two-dimensional heterostructures with bismuth selenide and tungsten selenide nanosheets as photothermal nanoagents. Near-infrared photothermal conversion of selenide heterostructure nanosheets can reach up to 40.75% under 808 nm excitation. It is known that selenium is a critical element to human health. More importantly, our experiments with mice show that the heterostructure nanosheets have low toxicity and high biocompatibility both in vitro and in vivo. The nanoagents based on heterostructures can effectively realize photothermal tumor ablation. It is suggested that the developed selenide nanosheets have great potential application in cancer therapy.

Designing Nd-doped bismuth selenide nanosheets with boosted photothermal conversion for imaging guided cancer therapy

Rational design and preparation of multifunctional low dimensional nanomaterials are of great importance for in vivo imaging and safety therapy. Meanwhile, nanomaterials with good bio-compatible and effectively photothermal conversion are still demanded to be fabricated in biomedicine. In this work, we have developed two-dimensional bismuth selenide nanosheets as the imaging and photothermal nanoagents. Through doping engineering, the near infrared photothermal conversion of Nd doped nanosheets was boosted by 52 %, which is higher than many previous works. Besides, the prepared nanomaterials can realize infrared and in vivo computed X-ray tomography bioimaging, due to the rich optical-magnetic properties of Nd atoms. The in vitro and vivo experiments with mice display that the Nd doped nanosheets have low toxicity and high biocompatibility. More importantly, the nanomaterials can efficiently achieve photothermal tumor ablation. It is suggested that designed and developed nanosheets have promising applications for biomedicine.

Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy

Targeted phototheranostic nanosystems involving both cancer-specific near-infrared (NIR) fluorescence imaging and NIR light-induced phototherapy have shown great potential to improve cancer detection and treatment. In this study, a bifunctional nanocomplex based on low-molecular-weight hyaluronic acid (LMW-HA) and chitosan oligosaccharide lactate (COL) conjugating a zwitterionic NIR dye (ZW800-1) was rationally designed and prepared, and it was simultaneously used to enhance tumor accumulation and photothermal therapy (PTT). When HA-COL-ZW nanocomplexes were intravenously injected into mice bearing NCI-H460 tumors, HA-COL-ZW revealed increased tumor accumulation with prolonged tumor retention. Moreover, the ZW800-1 incorporated in HA-COL-ZW nanocomplexes showed excellent capability to convert NIR light into heat energy at the tumor site, acting as a PTT agent. Therefore, the targeted phototherapeutic HA-COL-ZW nanocomplex is a biocompatible and effective photothermal nanoagent, which could be a good candidate for future clinical use.

Photothermal nanoagent for anti-inflammation through macrophage repolarization following antibacterial therapy

Owing to the ignorable bacterial resistance, photothermal therapy (PTT) has been widely studied for bacterial infection. However, few research efforts have focused primarily on the simultaneous utilization of photothermal agents (PTAs) for anti-inflammatory therapy following PTT. Here, we developed a nano-sized PTA (BSA@MPN) through the self-assembly of Fe3+ and epigallocatechin-3-gallate (EGCG) by using BSA as the nanoreactor and colloidal stabilizer. Next, we assessed its photothermal and reactive oxygen species (ROS) scavenging properties. In addition, we evaluated its antibacterial and anti-inflammatory abilities through in vitro antibacterial and cellular assays, respectively. Finally, we tested its in vivo sterilization and anti-inflammatory effects. Firstly, BSA@MPN displayed good photothermal capacity due to the inherent photothermal ability of metal-phenolic networks (MPNs). Consequently, BSA@MPN showed excellent both in vitro and in vivo antibacterial capacities. Moreover, BSA@MPN exhibited outstanding anti-oxidative property owing to ROS scavenging effect of EGCG. As a result, it presented extraordinary both in vitro and in vivo anti-inflammatory efficiencies through promoting the repolarization of pro-inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages with the released EGCG. The research findings indicated that the prepared nanoagent has great potential to be used for combined antibacterial and anti-inflammatory treatments in future clinical applications.

Inhibition of Pro-Survival Autophagy Induced by Rare-Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors.

Manipulation of autophagic processes has emerged as a promising strategy for synergizing nanoagent-mediated photothermal therapy (PTT). Most of the current studies focus on improving PTT efficacy by inhibiting pro-survival autophagy induced by the heat generated from the photothermal process. However, autophagy induced by the nanoagents is usually ignored, which may weaken the effect of autophagy-mediated efficacy improvement in PTT if induced autophagy is pro-death. Therefore, this work aims at developing a nanoagent that is able to induce heat-synergetic pro-survival autophagy to optimize the efficacy of PTT. An approach is developed to coat carbon layer, polyethylenimine (PEI), and folic acid (FA) on NaYF4 :Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA, DCPF) nanoparticles successively, giving access to the nanoagent to induce pro-survival autophagy. The synthetic imaging-guided photothermal nanoagent displays outstanding targeting ability and biocompatibility based on the surface modification of PEI and FA. By using an autophagy inhibitor chloroquine, a conspicuously synergistic effect on DCPF-mediated PTT in vitro and in vivo tumor models (HeLa) is achieved. A promising strategy is presented here to enhance the efficacy of imaging-guided PTT by modulating the autophagy induced by the nanoagent.

Metallic Nanoparticle-Doped Oxide Semiconductor Film for Bone Tumor Suppression and Bone Regeneration.

Bone implants with the photothermal effect are promising for the treatment of bone tumor defects. Noble metal-based photothermal nanoagents are widely studied for their stable photothermal effect, but they are expensive and difficult to directly grow on implant surfaces. In contrast, non-noble metal photothermal nanoagents are economical but unstable. Herein, to develop a stable and economical photothermal film on bone implants, a Ni nanoparticle-doped oxide semiconductor film was grown in situ on Nitinol via the reduction of Ni-Ti-layered double hydroxides. Ni nanoparticles remained stable in the NiTiO3 structure even when immersed in fluid for 1 month, and thus, the film presented a reliable photothermal effect under near-infrared light irradiation. The film also showed excellent in vitro and in vivo antitumor performance. Moreover, the nanostructure on the film allowed bone differentiation of mouse embryo cells (C3H10T1/2), and the released Ni ions supported the angiogenesis behavior of human vein endothelial cells. Bone implantation experiments further showed the enhancement of osteointegration of the modified Nitinol implant in vivo. This novel multifunctional Nitinol bone implant design offers a promising strategy for the therapy of bone tumor-related defects.

Tumor immunosuppressive microenvironment modulating hydrogels for second near-infrared photothermal-immunotherapy of cancer.

Immunotherapy has recently been seen as a hopeful therapeutic device to inhibit tumor growth and metastasis, while the curative efficacy is limited by intrinsic immunosuppressive tumor microenvironment. Herein, we reported a tumor immunosuppressive microenvironment modulating hydrogel (TIMmH) platform to achieve second near-infrared (NIR-II) photothermal therapy (PTT) combined immunotherapy for durable inhibition of breast cancer. This TIMmH platform was synthesized through co-loading of NIR-II photothermal nanoagent and an immunoadjuvant cytosine-phosphateguanosine oligodeoxynucleotides (CpG ODNs) into the alginate hydrogel (ALG). Upon the administration of ALG into the tumor, the TIMmH was in situ formed via the coordination effect with Ca2+, locally encapsulating the semiconducting polymer nanoparticles (SPIIN) and CpG in the colloid, achieving to prolong the accumulation time and prevent the premature damage and release of immunotherapeutic agents. Upon 1064-nm photoirradiation, the TIMmHSD was able to elevate the intratumoral temperature for the ablation of tumors, which could induce the apoptosis of tumor cells and achieve thermal immune activation by regulating of an immunosuppressive microenvironment. The TIMmH-mediated combined treatment effectively suppressed the growths of breast cancers, and even acquired a sustained inhibition of the lung metastasis. This study provides a novel tumor immunosuppressive microenvironment modulating hydrogel platform with NIR-II photoexcited capacity for the safe, effective and durable lung metastasis-inhibiting breast cancer treatment.

Controlled Activation of TRPV1 Channels on Microglia to Boost Their Autophagy for Clearance of Alpha-Synuclein and Enhance Therapy of Parkinson's Disease.

Parkinson's disease (PD) is characterized with accumulation of Lewy bodies with a major component of fibrillar alpha-synuclein (α-syn). Herein, boosting PD therapeutic efficacy by enhancing the autophagy of microglia to phagocytose and degrade α-syn via controlled opening of their surface TRPV1 channels with rationally designed photothermal nanoagent is reported. The Cu2- x Se-anti-TRPV1 nanoparticles (CS-AT NPs) are fabricated to target the microglia and open their surface TRPV1 channels under the second near infrared (NIR-II) laser irradiation to cause influx of Ca2+ to activate ATG5 and Ca2+ /CaMKK2/AMPK/mTOR signaling pathway, which promote phagocytosis and degradation of α-syn. The CS-AT NPs are efficiently delivered by focused ultrasound into striatum of PD mice with high expression of TRPV1 receptors. The athletic ability of PD mice treated by CS-AT NPs and NIR-II irradiation is significantly improved due to the phagocytotic clearance of α-syn by microglia with enhanced autophagy. The enzyme tyrosine hydroxylase, ionized calcium binding adapter protein 1, glial fibrillary acidic protein, and pSer129-α-syn (p-α-syn) of treated PD mice are almost recovered to the normal levels of healthy mice. This study provides insights into the activation of microglial autophagy by targeting surface ion channels to improve the treatment of PD and other neurodegenerative diseases.

Silk sericin-decorated supramolecular photothermal nanocatalyst-based ferric sulfide for boosting high therapeutic performance of tumor cells

Non-invasive strategies such as phototherapy is popular way to inhibit the growth of tumor, and have gained more achievements due to its near-infrared laser auxiliary, deep penetration and high therapeutic effect. Herein, we constructed a green and high-efficient photothermal nanoagent (denoted SS@FeS) by skillfully integrating natural silk sericin (SS) protein and ferric sulfide nanoparticle into one nanoscale space. The obtained SS@FeS showed good water dispensability, high photothermal ability and excellent anticancer performance, and the SS protein was acted as a good reaction medium for maintain the forming, colloidal stability and hydrophilia of SS@FeS. As expected, the nanoagent could rapidly enter into cells and were distributed in lysosomes and mitochondria, producing an enhanced killing ability against 4T1 tumor cells by damaging mitochondria. Meanwhile, it showed a certain fenton reaction and could strengthen the photothermal therapy (PTT) of nanoagent, which could open a new door for the development of photothermal agent-based tumor treatment.

Ultrathin Nanosheet-Supported Ag@Ag2O Core-Shell Nanoparticles with Vastly Enhanced Photothermal Conversion Efficiency for NIR-II-Triggered Photothermal Therapy.

Photothermal therapy (PTT) working in the second near-infrared (NIR-II) region has aroused a huge interest due to its potential application in terms of clinical cancer treatment. However, owing to the lack of photothermal nanoagents with high photothermal conversion efficiency, NIR-II-driven PTT still suffers from poor efficiency and subsequent cancer recurrence. In this work, we show a new and highly efficient preparation approach for NIR-II photothermal nanoagents and tailor ultrathin layered double hydroxide (LDH)-supported Ag@Ag2O core-shell nanoparticles (Ag@Ag2O/LDHs-U), vastly improving NIR-II photothermal performance. A combination study (high-resolution transmission electron microscopy (HRTEM), extended X-ray absorption fine structure spectroscopy (EXAFS), and X-ray photoelectron spectroscopy (XPS)) verifies that ultrafine Ag@Ag2O core-shell nanoparticles (∼3.8 nm) are highly dispersed and firmly immobilized within ultrathin LDH nanosheets, and their Ag2O shell possesses abundant vacancy-type defects. These unique Ag@Ag2O/LDHs-U display an impressive photothermal conversion efficiency as high as 76.9% at 1064 nm. Such an excellent photothermal performance is likely attributed to the enhanced localized surface plasmon resonance (LSPR) coupling effect between Ag and Ag2O and the reduced band gap caused by vacancy-type defects in the Ag2O shell. Meanwhile, Ag@Ag2O/LDHs-U also show prominent photothermal stability, due to the unique supported core-shell nanostructure. Moreover, both in vitro and in vivo studies further confirm that Ag@Ag2O/LDHs-U possess good biocompatible properties and outstanding PTT therapeutic efficacy in the NIR-II region. This research shows a new strategy in the rational design and preparation of an efficient photothermal agent, which is helpful to achieve more accurate and effective cancer theranostics.

Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.Graphical

Oxygenic Enrichment in Hybrid Ruthenium Sulfide Nanoclusters for an Optimized Photothermal Effect.

Transition-metal dichalcogenide (TMD)-based nanomaterials have been extensively explored for the photonic therapy. To the best of our knowledge, near-infrared (NIR) light is a requirement for the photothermal therapy (PTT) to achieve the feature of deep-tissue penetration, whereas no obvious absorption peaks existing in the NIR region for existing TMD nanomaterials limit their therapeutic efficacy. As one category of TMD nanomaterials, ruthenium sulfide-based nanomaterials have been less exploited in biomedical applications including tumor therapy so far. Here, we develop a facile biomineralization-assisted bottom-up strategy to synthesize oxygenic hybrid ruthenium sulfide nanoclusters (RuSx NCs) by regulating the oxygen amounts and sulfur defects for the optimized PTT. By regulating the increasing initial molar ratios of Ru to S, RuSx NCs with small sizes were endowed with increasing oxygen contents and sulfur defects, leading to the photothermal conversion efficiency (PCE) increasing from 32.8 to 41.9%, which were higher than that of most small-sized inorganic photothermal nanoagents. In contrast to commercial indocyanine green, these RuSx NCs exhibited higher photostability under NIR laser irradiation. The high PCE and superior photostability allowed RuSx NCs to effectively and completely ablate cancer cells. Thus, the proposed defect engineering strategy endows RuSx NCs with an excellent photothermal effect for the PTT of tumors of living mice, which also proves the potential of further exploring the properties of RuSx NCs for future biomedical applications.

Enhanced Antibacterial Activity of CuS-BSA/Lysozyme under Near Infrared Light Irradiation.

The synthesis of multifunctional photothermal nanoagents for antibiotic loading and release remains a challenging task in nanomedicine. Herein, we investigated a simple, low-cost strategy for the preparation of CuS-BSA nanoparticles (NPs) loaded with a natural enzyme, lysozyme, as an antibacterial drug model under physiological conditions. The successful development of CuS-BSA NPs was confirmed by various characterization tools such as transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Lysozyme loading onto CuS-BSA NPs was evaluated by UV/vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FTIR), zeta potential, and dynamic light scattering measurements. The CuS-BSA/lysozyme nanocomposite was investigated as an effective means for bacterial elimination of B. subtilis (Gram-positive) and E. coli (Gram-negative), owing to the combined photothermal heating performance of CuS-BSA and lysozyme release under 980 nm (0.7 W cm−2) illumination, which enhances the antibiotic action of the enzyme. Besides the photothermal properties, CuS-BSA/lysozyme nanocomposite possesses photodynamic activity induced by NIR illumination, which further improves its bacterial killing efficiency. The biocompatibility of CuS-BSA and CuS-BSA/Lysozyme was elicited in vitro on HeLa and U-87 MG cancer cell lines, and immortalized human hepatocyte (IHH) cell line. Considering these advantages, CuS-BSA NPs can be used as a suitable drug carrier and hold promise to overcome the limitations of traditional antibiotic therapy.