Hollow Copper Sulfide Nanoparticles Research Articles

A dual-mode portable platform with spatiotemporal temperature–pressure signal readouts for ultrasensitive quantitative determination of cancer cells

Early precise diagnosis of cancer is a prerequisite for cancer-related mortality and improved therapeutic outcomes. Direct quantitative cancer cell detection technologies show a great potential for early screening and diagnosis of cancer. However, the reported techniques generally involve exorbitant costs, lengthy procedures, and inevitable use of large-scale apparatus. We develop herein a spatiotemporal dual-mode sensing platform based on temperature and pressure signals for rapid, sensitive, and straightforward quantitative detection of cancer cells. Specifically, this platform is constructed by a dual-signal response probe consisting of hyaluronic acid (HA)-modified hollow copper sulfide nanoparticles (CuS@HA NPs), which not only elicits a robust and spatiotemporal photothermal effect via localized surface plasmon resonance (LSPR) but also promotes a rapid photothermal decomposition of NH4HCO3. This dual-signal response probe demonstrates a broad detection range from 10 to 105 cells/mL for sensing triple-negative breast cancer cells (MDA-MB-231) due to the specific recognition between HA and CD44 receptors. Notably, the remarkable sensitivities, with detection limits of 9 and 4 cells/mL for temperature and pressure signal readouts respectively, display about one order of magnitude lower than conventional immunoassay methods. The practicability and high reliability of the proposed strategy are further validated via analyzing clinic serum samples. Moreover, the localized photothermal therapy induced by the specific binding of CuS@HA NPs can realize targeted elimination of cancer cells. Overall, the developed dual-mode sensing platform demonstrates significant potential as a facile yet robust strategy for real-time and on-site determination of cancer cells in actual samples.

Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy.

Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.

Photothermal-Ionic-Pharmacotherapy of Myocardial Infarction with Enhanced Angiogenesis and Antiapoptosis.

Promoting angiogenesis is an effective therapeutic strategy to repair damaged hearts after myocardial infarction (MI). Copper ions and mild heat (41-42 °C) have been shown to promote angiogenesis, but their efficacy in MI is unknown. Here, a multicomponent hydrogel (EDR@PHCuS HG) is developed by encapsulating edaravone (EDR, a free radical scavenger) loaded porous hollow copper sulfide nanoparticles (PHCuS NPs) in a hyaluronic acid hydrogel (HG). Exposed to 808 nm near-infrared (NIR) light irradiation, the EDR@PHCuS HG exhibits controlled copper-ion release and mild photothermal effect to synergistically promote angiogenesis. In addition, released EDR inhibits cardiomyocyte apoptosis to further repair hearts. In the mouse model of MI, treatment with the EDR@PHCuS HG under an 808 nm laser significantly recovers the cardiac function and inhibits ventricular remodeling. This platform elucidates the cardioprotective effects of copper ions and mild heat and will provide a highly efficient treatment for MI.

Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. Invitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis

The application of photothermal therapy (PTT) is greatly limited by the low accumulation of photothermal agents, uneven photothermal distribution, and heat endurance of cancer cells. Worse still, despite PTT enhances immunogenicity, the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death (ICD) induction and poor infiltration of immune cells. To solve the above problems of PTT, we developed hyaluronic acid (HA) modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate (DDTC) to construct a breast tumor targeting and near infrared (NIR) photo-responsive drug delivery system (D-HCuS@HA), which further combined with losartan to improve the accumulation and penetration in the tumor site. Upon irradiation, D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)2 to eliminate heat endurance tumor cells, thereby enhancing anti-tumor effect and inducing effective ICD. Moreover, the combination with losartan could remodel the tumor microenvironment, allowing more T cells to infiltrate into the tumor, and significantly inhibiting the occurrence and development of metastatic tumors. In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan, which provides a new paradigm for anti-tumor and anti-metastases.

Carboxymethyl β-cyclodextrin grafted hollow copper sulfide@mesoporous silica carriers for stimuli-responsive pesticide delivery

Stimuli-responsive controlled release systems have received extensive attention to improve the pesticide bioavailability and minimize environmental pollution. Herein, a multiple stimuli-responsive IMI@HCuS@mSiO2 @ -ss-CβCD delivery system was constructed using modified carboxymethyl β-cyclodextrin (CβCD-ss-COOH) as sealing materials, hollow copper sulfide nanoparticles with amino-functionalized mesoporous silica shell (HCuS@mSiO2-NH2) as carriers and imidacloprid (IMI) as the model drug. The cavity structure of HCuS@mSiO2-NH2 would provide a large space for pesticide loading. The results revealed that HCuS@mSiO2-ss-CβCD was approximately 230 nm in size and the loading efficiency for IMI was 25.7%, and exhibited better biosafety on bacteria and seed. HCuS carriers were also served as photothermal agent and possessed high photothermal conversion effect (η = 38.4%). IMI@HCuS@mSiO2 @ -ss-CβCD displayed excellent foliage adhesion and multiple stimuli-responsive release properties to pH, α-amylase, GSH, and NIR. The photostability of IMI embedded in CuS@mSiO2 @ -ss-CβCD was approximately 10 times that of IMI solution. This work provides an efficient nanoplatform for realizing pesticide delivery.

Engineered Biomimetic Copper Sulfide Nanozyme Mediates "Don't Eat Me" Signaling for Photothermal and Chemodynamic Precision Therapies of Breast Cancer.

The rapid development of nanomedicine has brought hope and confidence to the precise treatment of tumors. However, the efficacy of nanoparticle-mediated therapy is severely limited due to phagocytosis and clearance by macrophages. CD47 is a well-documented ″don't eat me″ signaling molecule that binds to the SIRPα receptor on the macrophage surface, inhibiting the phagocytic behavior of the macrophages. In this study, CD47-overexpressing cancer cell membranes were used to coat hollow copper sulfide nanoparticles. The nanoparticles were shown to have an extended circulatory half-life and to actively target breast cancer, leading to increased accumulation in the tumor tissue. An excellent photothermal therapeutic effect was produced by near-infrared laser irradiation. At the same time, β-lapachone within the nanoparticles generated large amounts of hydrogen peroxide in the tumor environment, which was then catalyzed by the copper sulfide nanozyme to cytotoxic hydroxyl radicals, exerting a chemodynamic therapeutic effect. This engineered biomimetic nanozyme, through the mediation of the ″don't eat me″ signal, achieved both photothermal and chemodynamic precision treatments of breast cancer, creating a new mode of safe and effective tumor treatment.

Injectable thermo-sensitive hydrogel loaded hollow copper sulfide nanoparticles for ROS burst in TME and effective tumor treatment.

Introduction: Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and β-lapachone (Lap) (CLH) for lung tumor treatment. Methods: The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu2+) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu2+ consumes the overexpressed GSH in TME and the generated Cu+ further exploits the TME characteristics to initiate nanocatalytic reactions for generating highly toxic hydroxyl radicals. In addition, in cancer cells overexpressing Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase 1 (NQO1), Lap can catalyze the generation of hydrogen peroxide (H2O2) through futile redox cycles. H2O2 is further converted into highly toxic hydroxyl radicals via the Fenton-like reaction, leading to a burst of reactive oxygen species in TME, which further enhances the therapeutic effect of chemokines. Results: Analysis of the antitumor efficacy in a subcutaneous A549 lung tumor model mice showed a significant delay in tumor growth and no systemic toxicity was detected. Discussion: In conclusion, we have established a CLH nanodrug platform that enables efficient lung tumor therapy through combined photothermal/chemodynamic therapy (CDT) treatment and self-supplying H2O2 to achieve cascade catalysis, leading to explosive amplification of oxidative stress.

Flower-like Cu9S8 nanocatalysts with highly active sites for synergistic NIR-II photothermal therapy and chemodynamic therapy.

Chemodynamic therapy (CDT) is a promising reactive oxygen species-based therapeutic strategy for tumor therapy. However, the poor reaction kinetics of CDT agents severely restricts its further application. Herein, protamine stabilized flower-like Cu9S8 (PS@Cu9S8) nanocatalysts are fabricated via a one-pot biomineralization strategy for synergistic second near-infrared (NIR-II) photothermal therapy (PTT) and CDT of tumor. The PS@Cu9S8 nanocatalysts possess a high surface area (40.10 m2 g-1), which is higher than those of the previously reported solid and hollow copper sulfide nanoparticles. The high surface area of PS@Cu9S8 nanocatalysts increases the number of active sites during the Fenton-like reaction, thereby accelerating the efficiency of CDT. Meanwhile, the PS@Cu9S8 nanocatalysts show a high extinction coefficient (21.41 L g-1 cm-1) and photothermal conversion efficiency (42.34%), which results in an outstanding PTT efficiency and facilitate ˙OH generation for CDT. Furthermore, RNA-sequencing unveils the whole-genome expression change of 4T1 cells after PS@Cu9S8 nanocatalyst treatment, revealing the apparent changes in ROS, cell cycle, and apoptosis-related pathways. In vivo experiments proved the good therapeutic efficiency and negligible systematic toxicity of PS@Cu9S8 nanocatalysts. This work not only develops a superior multifunctional nanocatalyst for synergistic PTT and CDT of tumor, but also provides a facile approach to construct high-performance agents for cancer therapy.

Disulfiram-loaded hollow copper sulfide nanoparticles show anti-tumor effects in preclinical models of colorectal cancer

Colorectal cancer is one of the most common malignancies causing the majority of cancer-related deaths. There is an urgent need to develop new anticancer modalities. Recently, efforts have been made to turn clinically approved drugs into anticancer agents in specific tumor microenvironments via NPs. Disulfiram (DSF) as an effective copper (Cu2+)-dependent anti-tumour drug, which has been more widely used in antitumor research. Here, we constructed a novel therapeutic nanoplatforms, DSF@CuS, by encapsulating DSF in hollow CuS NPs to enable in situ chemoselective activation of DSF and hyperthermal amplified chemotherapy. The anticancer effect of DSF was enhanced by the thermal energy generated under NIR irradiation through the intrinsic photothermal conversion of CuS. As a result, significant apoptosis was induced in vitro, and tumor elimination was achieved in vivo. Collectively, DSF@CuS combined with photothermal therapy can significantly promote the apoptosis of CT26 colorectal cancer cells both in vitro and in vivo, providing a potential theoretical agent for the treatment of colorectal cancer.

Neutrophil-erythrocyte hybrid membrane-coated hollow copper sulfide nanoparticles for targeted and photothermal/ anti-inflammatory therapy of osteoarthritis

Osteoarthritis (OA), as a chronic degenerative joint disorder, has seriously affected the life quality of patients. Despite lots of drug treatment strategies that have been studied, the therapeutic effect is still unsatisfactory due to the lack of prolonged circulation life and targeted delivery ability. Recently, functional cell membranes modified nanoparticles have been explored to achieve high-efficiency drug delivery. Herein, neutrophil-erythrocyte hybrid membranes-coated dexamethasone sodium phosphate (Dexp)-loaded hollow copper sulfide nanoparticles (D-CuS@NR NPs) were fabricated for OA treatment. Generally, we achieved the synergistic treatment of mild-heating, prolonged circulation, and targeted delivery in this system. In particular, this biomimetic nanoparticle showed significant cytocompatibility and anti-inflammatory ability in vitro due to cell membrane coating and photothermal responsive drug release under NIR irradiation. Importantly, in vivo explorations revealed that D-CuS@NR NPs combined with photothermal treatment obtained an excellent therapy effect for preventing the OA process. Hence, this novel hybrid membranes-coated CuS NPs showed significant therapeutic efficacy by local warming and targeted drug delivery , which might become a promising drug delivery vehicle for improving the therapeutic effect of OA. • This nanoparticle possesses lots of advantages, including long circulation effect, excellent target ability, and well photothermal conversion efficiency. • Combined with NIR treatment, this drug loaded nanoparticle gained outstanding anti-inflammatory effect and ability to protect articular cartilage in vivo . • This drug loaded nanoparticle provides a promising platform for inflammation related diseases.

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

Hyaluronic acid-modified manganese dioxide-enveloped hollow copper sulfide nanoparticles as a multifunctional system for the co-delivery of chemotherapeutic drugs and photosensitizers for efficient synergistic antitumor treatments

This paper presents the design of a new type of intelligent and versatile all-in-one therapeutic nanoplatform for the co-delivery of chemotherapeutic drugs and photosensitizers to facilitate multimodal antitumor treatment; the system is based on hyaluronic acid (HA)-modified manganese dioxide (MnO2)-enveloped hollow porous copper sulfide (CuS) nanoparticles (CuS@MnO2/HA NPs). In this system, a CuS inner shell allows for the co-loading of doxorubicin (DOX) and indocyanine green (ICG) and induces photothermal effects, and a biodegradable MnO2 external shell affords on-demand tumor microenvironment (TME)-triggered release and catalase- andFenton-like activities. Moreover, the HA modification endows the system with a CD44 receptor-mediated tumor-targeting property. The formulated DOX and ICG co-loaded CuS@MnO2/HA (DOX/ICG-CuS@MnO2/HA) NPs were found to exhibit excellent photothermal performance both in vitro and in vivo. In addition, DOX/ICG-CuS@MnO2/HA NPs were found to display both TME and near-infrared (NIR)-responsive controlled release properties. The NPs also have a superior reactive oxygen species (ROS) generation capacity due to the combination of enhanced ICG-induced singlet oxygen and CuS@MnO2-mediated hydroxyl radicals. The cellular uptake, fluorescence imaging property, cytotoxicity, and thermal imaging of these NPs were also evaluated. In tumor-bearing mice, the DOX/ICG-CuS@MnO2/HA NPs displayeda superior antitumor efficacy (2.57-fold) as compared with free DOX. Therefore, the developed DOX/ICG-CuS@MnO2/HA NPs have a great potential for use as an all-in-one nanotherapeutic agent for the efficient and precise induction of chemo/photothermal/photodynamic/chemodynamic therapy with superior antitumor efficacy and fewer side effects.

Nanomedicine Enables Drug-Potency Activation with Tumor Sensitivity and Hyperthermia Synergy in the Second Near-Infrared Biowindow

Disulfiram (DSF), a U.S. Food and Drug Administration (FDA)-approved drug for the treatment of chronic alcoholism, is also used as an antitumor drug in combination with Cu2+ ions. However, studies have shown that the endogenous Cu2+ dose in tumor tissues is still insufficient to form relatively high levels of a bis(N,N-diethyldithiocarbamate) copper(II) complex (denoted as Cu(DTC)2) to selectively eradicate cancer cells. Here, DSF-loaded hollow copper sulfide nanoparticles (DSF@PEG-HCuSNPs) were designed to achieve tumor microenvironment (TME)-activated in situ formation of cytotoxic Cu(DTC)2 for NIR-II-induced, photonic hyperthermia-enhanced, and DSF-initiated cancer chemotherapy. The acidic TME triggered the gradual degradation of DSF@PEG-HCuSNPs, promoting the rapid release of DSF and Cu2+ ions, causing the in situ formation of cytotoxic Cu(DTC)2, to achieve efficient DSF-based chemotherapy. Additionally, DSF@PEG-HCuSNPs exhibited a notably high photothermal conversion efficiency of 23.8% at the second near-infrared (NIR-II) biowindow, thus significantly inducing photonic hyperthermia to eliminate cancer cells. Both in vitro and in vivo studies confirmed the effective photonic hyperthermia-induced chemotherapeutic efficacy of DSF by integrating the in situ formation of toxic Cu(DTC)2 complexes and evident temperature elevation upon NIR-II laser irradiation. Thus, this study represents a distinctive paradigm of in situ Cu2+ chelation-initiated "nontoxicity-to-toxicity" transformation for photonic hyperthermia-augmented DSF-based cancer chemotherapy.

Hybrid membrane camouflaged copper sulfide nanoparticles for photothermal-chemotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Biomimetic nanoparticles (NPs) coated with cell membranes show enhanced biocompatibility and specificity for homotypic cells, and have gained considerable attention for targeted anti-tumor therapy. We constructed cancer cell-macrophage hybrid membrane-coated near infrared (NIR)-responsive hollow copper sulfide nanoparticles encapsulating sorafenib and surface modified with anti-VEGFR (CuS-SF@CMV NPs). These CuS-SF@CMV NPs expressed the characteristic membrane proteins of both cancer cells and macrophages, and selectively accumulated in cancer cells in vitro and tumors in vivo, compared to the CuS NPs. In addition, the CuS-SF@CMV NPs achieved synergistic photo-thermal and chemotherapy in cancer cells upon NIR irradiation, with 94.3% inhibition of tumor growth in a murine hepatoma model. While the initial increase in temperature rapidly killed the tumor cells, sorafenib and the anti-VEGFR antibody sustained the tumor killing effect by respectively inhibiting tumor cell proliferation and angiogenesis via the Ras/Raf/MEK/ERK and PI3K/AKT pathways. Taken together, the CuS-SF@CMV NPs have immune evasion, tumor cell targeting and drug loading capacities, along with an inherent photo-thermal conversion ability, making them ideal for synergistic photo-thermal/chemo therapy against HCC. Statement of SignificanceWe created cancer cell-macrophage hybrid membrane-coated hollow CuS NPs encapsulating sorafenib and surface modified with anti-VEGFR antibodies (CuS-SF@CMV). These CuS-SF@CMV NPs enhanced synergistic PTT and chemotherapy against hepatoma cells through homotypic cell targeting, immune escape and inhibition of a tumorigenic signaling pathway. A long-term inhibition of tumor growth and metastasis was achieved owing to the rapid destruction of the cancer cells through photo-thermal conversion by the CuS NPs, and sustained clearance of the tumor cells by sorafenib and anti-VEGFR antibodies.Our findings suggest that CuS-SF@CMV NPs present great treating effects in preclinical models of HCC, providing the framework for further study in clinical trials to improve patient outcome in hepatocellular carcinoma.

Graphene quantum dots-decorated hollow copper sulfide nanoparticles for controlled intracellular drug release and enhanced photothermal-chemotherapy

Graphene quantum dots (GQDs)-decorated hollow copper sulfide nanoparticles (CuS NPs) were developed as a multifunctional platform for controlled intracellular drug release and enhanced photothermal-chemotherapy. The CuS NPs were firstly synthesized to encapsulate anticancer drug doxorubicin (DOX) followed by the GQDs decoration on the surface of CuS NPs. The prepared NPs exhibited good crystal structure, uniform nanosize, excellent colloidal stability, high drug encapsulation and enhanced optical absorbance. Moreover, the drug release was successfully triggered from the DOX-CuS@GQDs NPs under high temperature and (near-infrared) NIR laser irradiation. Encouraged by this result, we moved to investigate the intracellular drug release behavior under NIR laser irradiation on MDA-MB-231 cells. The confocal images and flow cytometry analysis indicated a significant NIR-triggered DOX release within MDA-MB-231 cells after cellular uptake. Furthermore, the CuS NPs could readily convert light energy to heat to photothermally ablate the cancer cells under NIR laser irradiation, and the photothermal ablation effect was further enhanced by the capping of GQDs on CuS NPs. The combined photothermal therapy and chemotherapy of the prepared DOX-CuS@GQDs NPs also enabled a synergistic therapeutic effect on cancer cells. Therefore, the prepared DOX-CuS@GQDs NPs provided a novel promising platform for cancer therapy with controlled intracellular drug release and combined photothermal-chemotherapy.

Intracellular low-abundance microRNA imaging by a NIR-assisted entropy-driven DNA system.

Intracellular microRNA (miRNA) imaging remains a key challenge due to its low abundance. Herein, we integrate a rationally designed elegant entropy-driven DNA probe with assisted DNA fuel on hollow copper sulfide nanoparticles (HCuSNPs) for intracellular miRNA imaging. The anchored assisted DNA fuel strand could be efficiently released by a NIR-II laser irradiation induced photothermal effect of the HCuSNPs. The DNA machine was activated by target miRNA binding and powered by NIR-responsive released DNA fuel through toehold-mediated strand displacement reactions, accomplished by strong fluorescence recovery. It demonstrated 2 orders of magnitude improvement in the detection sensitivity compared to molecular beacons (MBs). Reliable intracellular low-abundance miRNA imaging among different cells and monitoring of down-regulated miRNA was realized without external enzyme or fuel addition. Oncogenic miRNA imaging in vivo was also realized. The entropy-driven DNA machine system provides a facile and powerful tool for intracellular miRNA analysis and related biomedical applications.

Erythrocyte-Cancer Hybrid Membrane Camouflaged Hollow Copper Sulfide Nanoparticles for Prolonged Circulation Life and Homotypic-Targeting Photothermal/Chemotherapy of Melanoma.

Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC-B16), and RBC-B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC-B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC-B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC-B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC-B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.

The combined therapeutic effects of 131iodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading 131I-labeled hollow copper sulfide nanoparticles and paclitaxel (131I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. 18F-fluordeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P<0.05) following intra-tumoral (i.t.) injection with 131I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by 131I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that 131I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, 131I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.

Enhanced reactive oxygen species through direct copper sulfide nanoparticle-doxorubicin complexation

CuS-based nanostructures loading the chemotherapeutic agent doxorubicin (DOX) exerted excellent cancer photothermal chemotherapy under multi-external stimuli. The DOX loading was generally designed through electrostatic interaction or chemical linkers. However, the interaction between DOX molecules and CuS nanoparticles has not been investigated. In this work, we use PEGylated hollow copper sulfide nanoparticles (HCuSNPs) to directly load DOX through the DOX/Cu2+ chelation process. Distinctively, the synthesized PEG–HCuSNPs–DOX release the DOX/Cu2+ complexes into surrounding environment, which generate significant reactive oxygen species (ROS) in a controlled manner by near-infrared laser. The CuS nanoparticle-mediated photothermal ablation facilitates the ROS-induced cancer cell killing effect. Our current work reveals a DOX/Cu2+-mediated ROS-enhanced cell-killing effect in addition to conventional photothermal chemotherapy through the direct CuS nanoparticle-DOX complexation.