Plasmonic and Photothermal Effects of CuS Nanoparticles Biosynthesized from Acid Mine Drainage with Potential Drug Delivery Applications.

In this work, the plasmonic and photothermal effects of CuS nanoparticles biosynthesized from acid mine drainage (AMD) were studied. CuS were formed by delivering the H2S generated by a sulfidogenic bioreactor to an off-line system containing the AMD. The precipitates collected after contact for an hour were washed and physico-chemically characterized, showing a nanoparticle with a mean diameter of 33 nm, crystalline nature and semiconductor behavior with a direct band gap of 2.2 eV. Moreover, the CuS nanoparticles exhibited localized surface plasmonic resonance in the near infrared range, with a high absorption band centered at 973 nm of wavelength, which allowed an increase in the temperature of the surrounding media under irradiation. Finally, the cytotoxicity of the CuS nanoparticles as well as their potential use as part of drug delivery platforms were investigated.

Enhanced production of amylase, pyruvate and phenolic compounds from glucose by light-driven Aspergillus niger-CuS nanobiohybrids.

BACKGROUND: The demand for value-added compounds such as amylase, pyruvate and phenolic compounds produced by biological methods has prompted the rapid development of advanced technologies for their enhanced production. Nanobiohybrids (NBs) make use of both the microbial properties of whole-cell microorganisms and the light-harvesting efficiency of semiconductors. Photosynthetic NBs were constructed that link the biosynthetic pathways of Aspergillus niger with CuS nanoparticles. RESULTS: In this work, NB formation was confirmed by negative values of the interaction energy, i.e., 2.31 × 108 to -5.52 × 108 kJ mol-1 for CuS-Che NBs, whereas for CuS-Bio NBs the values were -2.31 × 108 to -4.62 × 108 kJ mol-1 for CuS-Bio NBs with spherical nanoparticle interaction. For CuS-Bio NBs with nanorod interaction, it ranged from -2.3 × 107 to -3.47 × 107 kJ mol-1 . Further, the morphological changes observed by scanning electron microscopy showed the presence of the elements Cu and S in the energy-dispersive X-ray spectra and the presence of CuS bonds in Fourier transform infrared spectroscopy indicate NB formation. In addition, the quenching effect in photoluminescence studies confirmed NB formation. Production yields of amylase, phenolic compounds and pyruvate amounted to 11.2 µmol L-1, 52.5 µmol L-1 and 28 nmol µL-1, respectively, in A. niger-CuS Bio NBs on the third day of incubation in the bioreactor. Moreover, A niger cells-CuS Bio NBs had amino acids and lipid yields of 6.2 mg mL-1 and 26.5 mg L-1, respectively. Furthermore, probable mechanisms for the enhanced production of amylase, pyruvate and phenolic compounds are proposed. CONCLUSION: Aspergillus niger-CuS NBs were used for the production of the amylase enzyme and value-added compounds such as pyruvate and phenolic compounds. Aspergillus niger-CuS Bio NBs showed a greater efficiency compared to A. niger-CuS Che NBs as the biologically produced CuS nanoparticles had a higher compatibility with A. niger cells. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).

NIR II-Excited and pH-Responsive Ultrasmall Nanoplatform for Deep Optical Tissue and Drug Delivery Penetration and Effective Cancer Chemophototherapy.

The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.

Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors.

Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r1 relaxivity (∼60.0 mM-1 s-1 per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after intravenous injection into mice, creating opportunities for fluorescence/MR bimodal imaging-guided PTT of subcutaneous and metastatic gastric tumors. For the first time, accurate detection and laser irradiation-initiated photothermal ablation of orthotopic gastric tumors in intraoperative mice was also achieved. This study highlights the versatility of using a combination of dual biomarker recognition (i.e., αvß3 and MMP-2) and dual modality imaging (i.e., MRI and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.

CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance.

Bypass signaling activation plays a crucial role in the acquired resistance of gefitinib, the first targeted drug in the clinic to treat advanced non-small cell lung cancer. Although the inactivation of bypass signaling by small-molecule inhibitors or monoclonal antibodies may overcome gefitinib resistance, their clinical use has been limited by the complex production process and off-target toxicity. Here we show CuS nanoparticles (NPs) behaved as a photodynamic nanoswitch to specifically abrogate overactive bypass signaling in resistant tumor cells without interfering with the same signal pathways in normal cells. In representative insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistant tumors, CuS NPs upon near-infrared laser irradiation locally elevated reactive oxygen species (ROS) level in tumor cells, leading to the blockage of bypass IGF1R and its downstream AKT/ERK/NF-κB signaling cascades. Consequently, laser-irradiated CuS NPs sensitized tumors to gefitinib treatment and prolonged the survival of mice with no obvious toxicity. Laser-irradiated CuS NPs may serve as a simple and safe nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in a specific and controllable manner and provide insights into the treatment of a myriad of other resistant tumors in the field of cancer therapy.

The regulation of CuSNPs' interface for further enhancing mechanical and photothermal conversion properties of chitosan/@CuSNPs hybrid fibers.

Our previous study has demonstrated that the microstructure of copper sulfide nanoparticles (CuSNPs) can be controlled to enhance mechanical and photothermal conversion properties of chitosan (CS)/CuSNPs hybrid fibers. However, achieving optimal dispersion and compatibility of CuSNPs within a CS matrix remains a challenge, this study aims to improve dispersion and compatibility by modifying the CuSNPs' interface, thereby enhancing mechanical and photothermal conversion properties of hybrid fibers. The interfaces of @CuSNPs (CuS@Xylan NPs, CuS@SA NPs, and CuS@PEG NPs) contain hydroxyl groups, facilitating the hydrogen bonds formation with the CS matrix. The dispersibility is further enhanced by the synergistic effect of xylan and SA's anionic charges with cationic chitosan. Notably, the viscosity of the CS/@CuSNPs hybrid spinning solution is significantly enhanced, resulting in improved breaking strength for initial hybrid fibers. Specifically, the breaking strength of CS/CuS@Xylan NPs hybrid fibers reaches 1.4 cN/dtex, exhibiting a 42.86 % and 20.6 % increase over CS and CS/CuSNPs hybrid fibers. Simultaneously, the CS/CuS@Xylan NPs hybrid fibers exhibit exceptional photothermal conversion performance, surpassing that of CS fibers by 5.2 times and CS/CuSNPs hybrid fibers by 1.4 times. The regulation of interface modification is an efficient approach to enhance the tensile strength and photothermal conversion properties of CS/CuSNPs hybrid fibers.

Amino acid-mediated amorphous copper sulphide with enhanced photothermal conversion efficiency for antibacterial application.

Pathogenic bacteria in daily life, such as Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), often seriously affect human life and health. The extensive use of antibiotics has led to the emergence of drug-resistant bacteria, so it is urgent to develop efficient and non-drug-resistant sterilization methods. Here, we use small-molecule cysteine (Cys) as an auxiliary agent to synthesize spherical porous amorphous CuS-Cysteine (CuS-C) nanoparticles, which have good dispersion in aqueous solutions, and explore the reaction mechanism of Cys-induced CuS synthesis. The synthesized composite nanomaterials have strong near-infrared light absorption ability and efficient photothermal conversion ability and can effectively ablate pathogenic bacteria under the irradiation of an 808 nm laser. In addition, antibacterial experiments showed that CuS-C composites had no bactericidal effect without near-infrared light, but they had a good photothermal bactericidal effect on S. aureus and E. coli under radiation conditions. Considering the simple synthesis process, strong photothermal conversion ability, low cost, and suitability for large-scale production, CuS-C nanocomposites, as a promising antibacterial material, will provide a feasible scheme for the treatment of drug-resistant pathogens.

Near-infrared-responsive GE11-CuS@Gal nanoparticles as an intelligent drug release system for targeting therapy against oral squamous cell carcinoma.

Galangin (Gal) is a natural plant flavonoid. More and more evidence shows that Gal can achieve anti-tumor effects by regulating various mechanisms. However, its poor water solubility, low bioavailability, and insufficient lesion targeting limit its clinical application. To overcome these shortcomings, we designed and developed a mesoporous nanosystem (GE11-CuS) that actively located the target area and photo-controlled drug release, which promoted the rapid accumulation of drugs in tumor tissues under NIR irradiation, thus achieving positive effects against cancer. In this study, we explored the application of the Gal-loaded nanometer system (GE11-CuS@Gal) in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. The results exhibited that GE11-CuS@Gal had excellent targeting ability and could accumulate efficiently in tumor cells (HSC-3). Meanwhile, the temperature of GE11-CuS@Gal increasing rapidly under NIR illumination damaged the integrity of the carrier and allowed Gal molecules to escape from the pores of the nanoparticles. When the accumulation of Gal in the nidus reached a certain level, the intracellular ROS level could be significantly increased and the antioxidative stress pathway mediated by Nrf2/OH-1 was effectively blocked, to inhibit the growth and migration of tumors. In conclusion, the GE11-CuS improved the antitumor activity of Gal in the body, which laid a foundation for the treatment of OSCC with traditional Chinese medicine ingredients.

Polyphosphate-Mediated Crystallographic and Colloidal Stabilization of CuS Nanoparticles: Enhanced NIR-Responsive Chemo-Photothermal Efficacy.

Photothermal therapy (PTT) is an emerging treatment modality for cancer management. However, the photothermal agents (PTAs) used in PTT should have sufficient biocompatibility, water dispersibility, and good photoresponsive. In this aspect, water-dispersible and biocompatible linear polyphosphate (LP)-functionalized CuS nanoparticles (LP-CuS NPs) were developed using sodium tripolyphosphate (LP molecule) as a surface passivating agent. The successful formation of the green covellite CuS phase was confirmed by X-ray diffraction and TEM analyses, and its surface functionalization with the LP ligand was evident from X-ray photoelectron spectroscopy, Fourier transform infrared, thermogravimetric analysis, and light scattering measurements. It has been found that the use of LP not only stabilizes the crystallographic covellite CuS phase by overcoming the requirement of a soft ligand but also provides long-term aqueous colloidal stability, which is essential for PTT applications. The aqueous suspension of LP-CuS NPs showed excellent heating efficacy under near infrared (NIR) light irradiation (980 nm) and has a strong binding affinity towards anticancer drug, doxorubicin hydrochloride (DOX). The drug-loaded systems (DOX@LP-CuS NPs) revealed a pH-dependent drug release behavior with higher concentrations in a mild acidic environment. The in vitro studies showed substantial cellular uptake of DOX-loaded systems in cancer cell lines and enhanced toxicity towards them upon irradiation of NIR light through apoptotic induction, suggesting their potential application in chemo-photothermal therapy.

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Near-infrared-responsive CuS@Cu-MOF nanocomposite with high foliar retention and extended persistence for controlling strawberry anthracnose.

Strawberry anthracnose (Colletotrichum gloeosporioides) exhibits a high pathogenicity, capable of directly infecting leaves through natural openings, resulting in devastating impacts on strawberries. Here, nanocomposite (CuS@Cu-MOF) was prepared with a high photothermal conversion efficiency of 35.3% and a strong response to near-infrared light (NIR) by locally growing CuS nanoparticles on the surface of a copper-based metal-organic framework (Cu-MOF) through in situ sulfurization. The porosity of Cu-MOF facilitated efficient encapsulation of the pesticide difenoconazole within CuS@Cu-MOF (DIF/CuS@Cu-MOF), achieving a loading potential of 19.18 ± 1.07%. Under NIR light irradiation, DIF/CuS@Cu-MOF showed an explosive release of DIF, which was 2.7 times higher than that under dark conditions. DIF/CuS@Cu-MOF exhibited a 43.9% increase in efficacy against C. gloeosporioides compared to difenoconazole microemulsion (DIF ME), demonstrating prolonged effectiveness. The EC50 values for DIF and DIF/CuS@Cu-MOF were 0.219 and 0.189 µg/mL, respectively. Confocal laser scanning microscopy demonstrated that the fluorescently labeled CuS@Cu-MOF acted as a penetrative carrier for the uptake of hyphae. Furthermore, DIF/CuS@Cu-MOF exhibited more substantial resistance to rainwater wash-off than DIF ME, with retention levels on the surfaces of cucumber leaves (hydrophilicity) and peanut leaves (hydrophobicity) increasing by 36.5-fold and 9.4-fold, respectively. These findings underscore the potential of nanocomposite to enhance pesticide utilization efficiency and leaf retention.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release.

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

Multifunctional Fe3O4@CuS nanoparticle-driven colorimetric and photothermal immunochromatographic test strip for the sensitive detection of Salmonella typhimurium in milk.

Magnetic nanoparticles are widely employed as signal labeling reporters in immunochromatographic test strips (ICTS) for detecting foodborne pathogens due to their outstanding anti-interference and magnetic enrichment performance. However, the insufficient colorimetric signal brightness of magnetic nanoparticles results in poor sensitivity, hindering their ability to meet the growing demand for advanced ICTS. Herein, we synthesized Fe3O4@CuS core-shell structure nanoparticles using a facile in-situ growth method. These Fe3O4@CuS nanoparticles exhibit a superior photothermal conversion efficiency of 42.12 % and a magnetization strength of 35 emu/g. We developed a dual-readout format ICTS based on Fe3O4@CuS, incorporating both colorimetric and photothermal formats to enhance sensitivity for Salmonella typhimurium detection. The limit of detection for Fe3O4@CuS-ICTS in the colorimetric and photothermal format was 5 × 104 CFU/mL and 7.7 × 10³ CFU/mL, respectively. Additionally, the average recoveries ranged from 91.25 % to 103.39 %, with variations from 2.2 % to 11.1 %, demonstrating good accuracy and precision. Therefore, this work suggests that Fe3O4@CuS nanoparticles, with their superior magnetic, optical, and photothermal properties, can serve as promising signal labeling reporters to improve the detection performance of ICTS and hold potential for constructing more accurate and sensitive point-of-care testing platforms.

Hollow CuS nanoparticles equipped with hydroxyapatite/hyaluronic acid coating for NIR/pH dual-responsive drug delivery.

The near-infrared (NIR)/pH dual-responsive nanoplatform shows great potential in remote photothermal therapy for tumor on account of the near-infrared window in biological tissue and the mild acidic environment in tumor cells. CuS nanoplatform has become a rising star in the field of photothermal agents due to its excellent NIR responsiveness and photostability. In this work, hollow CuS nanoparticles with high photothermal conversion efficiency (42.42 %) were synthesized through a novel surfactant micelle-assisted method. Then, CuS@hydroxyapatite (HAP)/hyaluronic acid (HA) nanoclusters with controllable drug release property were prepared by capping HAP and HA on the surface of CuS via electrostatic self-assembly approach. The hollow structure of CuS and the large specific surface area of HAP ensure an outstanding doxorubicin hydrochloride (DOX) loading efficiency of 99.2 % in CuS@HAP/HA nanoclusters. The introduction of HA effectively retards the initial burst release of DOX and ensures the excellent biocompatibility of nanoclusters. More importantly, CuS@HAP/HA displays distinct NIR/pH dual-responsive drug release properties owing to the excellent NIR responsiveness of hollow CuS and the gradual dissolution of HAP under acidic conditions. This work provides an environmentally benign method to prepare CuS-based nanoclusters with excellent NIR/pH responsive drug delivery properties, which has great potential in remote photothermal therapy.

Protease-Loaded CuS Nanoparticles with Synergistic Photothermal/Dynamic Therapy against F. nucleatum-Induced Periodontitis.

Periodontitis is a chronic inflammatory disease induced by a plaque biofilm, which can lead to the destruction of the periodontal support tissue and even teeth loss. The common strategies of periodontitis treatment are to eliminate bacterial/biofilm-related inflammation and subsequently inhibit alveolar bone resorption, for which antibiotic therapy is the most traditional one. However, impenetrable polymeric substances on bacterial biofilms make it difficult for traditional antimicrobial agents to take effect. In this study, a novel nanoparticle protease-loaded CuS NPs was developed, combining the advances of photodynamic and photothermal therapy from CuS and enzymatic degradation of the biofilm by a protease. The photothermal activity and the reactive oxygen generation capacity of the designed nanoparticles were verified by the experimental results, constituting the basis of antibacterial function. Next, the high antimicrobial activity of CuS@A NPs onFusobacterium nucleatumand its biofilm was demonstrated. The proper hemo/cytocompatibility of CuS-based NPs was demonstrated by in vitro assays. Last, effective treatment against periodontitis was achieved in a rat periodontitis model through the significant efficacy of inhibiting bone resorption and alleviating inflammation. Thus, the developed CuS@A NPs prove a promising material for the management of periodontitis.

Bio-recovery of CuS nanoparticles from the treatment of acid mine drainage with potential photocatalytic and antibacterial applications.

In the present work, CuS nanoparticles were biorecovered from a real acid mine drainage (AMD) and its photocatalytic and antibacterial activities were studied. CuS were formed by delivering biogenic H2S produced by a continuous sulfidogenic bioreactor to an off-line vessel containing the AMD. The main physico-chemical properties of CuS nanoparticles were analyzed by UV-vis spectroscopy, TEM, FE-SEM, XRD and XPS. Moreover, its photocatalytic activity on the photodegradation of organic dyes in water and its antibacterial activity against several bacterial strains were studied and compared with CuS nanoparticles synthetized from a CuSO4 aqueous solution based on the same synthesis method. CuS nanoparticles from the real AMD showed similar physico-chemical properties and photocatalytic and antibacterial activities in comparison to CuS nanoparticles formed with the copper solutions. These results open the way to recover valorous CuS nanoparticles from AMD with potential industrial applications using a metal bioremediation process based on sulfidogenic bioreactors.

Multifunctional nanoparticles precisely reprogram the tumor microenvironment and potentiate antitumor immunotherapy after near-infrared-II light-mediated photothermal therapy.

Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy. However, mild PTT alone usually fails to activate the immune response and prevent tumor metastasis. Herein, a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an effective PTT effect in the second near-infrared (NIR-II) window, is developed. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response. Copper ions are released in the acidic TME to promote the M1 polarization of tumor-associated macrophages. The model antigen OVA not only acts as a scaffold for nanoparticle growth but also promotes the maturation of dendritic cells, which primes naive T cells to stimulate adaptive immunity. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, which suppresses tumor growth and metastasis in a mouse melanoma model. The proposed therapeutic platform, CuS@OVA nanoparticles, may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies. STATEMENT OF SIGNIFICANCE: Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy, but usually fails to activate the immune response and prevent tumor metastasis. Herein, we develop a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an excellent PTT effect in the second near-infrared (NIR-II) window. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response by promoting the M1 polarization of tumor-associated macrophages and the maturation of dendritic cells. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, suppressing tumor growth and metastasis. The platform may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies.

Composite Hydrogel for Spatiotemporal Lipid Intervention of Tumor Milieu.

Induction of immunogenic cell death (ICD) plays crucial roles in cancer immunotherapy, whereas its efficacy is severely compromised by redundant antioxidant defenses in cancer cells and aberrant lipid metabolism in immunosuppressive cell populations. In this work, it is found that hollow mesoporous CuS nanoparticles (NPs) possess an intrinsic capacity of inhibiting glutathione peroxidase 4 (GPX4). When loaded with an inhibitor of the ferroptosis suppressor protein 1 (FSP1), these NPs block two parallel redox systems and cooperate with near-infrared irradiation to reinforce ICD. A hydrogel co-delivering cancer-cell-targeting CuS NPs and immunosuppressive-cell-targeting sulfo-N-succinimidyl oleate (SSO) for spatiotemporal lipid intervention i further fabricated. While the CuS NPs augment ICD via synergistic lipid peroxidation, SSO reinstates immune perception via lipid metabolic reprogramming, thereby coordinately triggering robust innate and adaptive immunity to restrain tumor growth, relapse, and metastasis. This study provides an immunometabolic therapy via orchestrated lipid modulation in the tumor milieu.

Eggshell membrane-mimicking multifunctional nanofiber for in-situ skin wound healing.

Eggshell membrane is a naturally-occurring protective barrier layer for chickens' incubation and shows the close similarity with extracellular matrix. To fully explore and utilize its' structure and active components via a mimicking way will be of great interest for wounds healing. Herein, the well-dispersed CuS nanoparticles were prepared by using eggshell membranes as templates with strong near-infrared absorption and photothermal properties. Furthermore, the as-prepared solution was combined with polyvinyl pyrrolidone and chitosan-derived fluorescent carbon dots for the mimetic synthesis of multifunctional nanofibrous membrane by a hand-held electrospinning device, which has the merits of in-situ operation, the extracellular matrix (ECM)-like architecture, hemostatic, radical scavenging, antibacterial, as well as accelerated healing of skin injury, etc. The electrospun-nanofiber membrane with optimal addition of 100 mg/L CuS nanoparticles was confirmed to be noncytotoxic on human fibroblasts and showed strong antibacterial activities against S. aureus and E. coli under NIR irradiation (980 nm). In addition, the radical scavenging ability was also proved by DPPH experiments. The animal experiments revealed that the nanofiber membrane could accelerate the wound healing process. The work lays down a simple and environmentally-friendly approach for the fabrication and development of promising wound healing materials in skin tissue engineering applications.

NIR-â ¡ window Triple-mode antibacterial Nanoplatform: Cationic Copper sulfide nanoparticles combined vancomycin for synergistic bacteria eradication.

The widespread use of antibiotics leads to the increasing drug resistance of bacteria and poses a threat to human health. Therefore, there is an urgent need to develop new antibacterial strategies. Herein, based on the good photothermal properties of Copper sulfide (CuS) nanoparticles under near infrared (NIR) laser, we developed a NIR-Ⅱ window triple-mode synergetic antibacterial cCuS (cationic CuS) @Vancomycin (Van) nanoplatform. In the proposed nanoplatform, the positive charge on the surface makes cCuS@Van nanoplatform show better bacterial uptake and membrane damage; vancomycin induces chemical sterilization and provides a targeting effect to the nanoplatform; combined with the strong photothermal effect and deep tissue penetration at the excitation of 1064 nm laser, cCuS@Van nanoplatform can effectively kill bacterial. The photothermal conversion efficiency of the nanoplatform can reach 49.12 % and in vitro experiments show a sterilizing rate of more than 99.5 % to staphylococcus aureus (S. aureus) at the concentration of 3.0 µM, which also demonstrated the synergistic effect of cCuS@Van nanoplatform. In addition, low cytotoxicity to human cells conforms the good biocompatibility of the as-prepared cCuS@Van nanoplatform, which endows it a good application prospect in the field of antibacterial, such as wound healing and implant sterilization.