Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide

Graphene has shown great potential both in photothermal therapy and drug delivery. Herein, we developed doxorubicin-loaded PEGylated nanographene oxide (NGO-PEG-DOX) to facilitate combined chemotherapy and photothermal therapy in one system. In this work, we studied the ablation of tumor both in vivo and in vitro by the combination of photothermal therapy and chemotherapy using this functional graphene oxide. The ability of the NGO-PEG-DOX nanoparticle to combine the local specific chemotherapy with external near-infrared (NIR) photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy. Furthermore, lower systematic toxicity of NGO-PEG-DOX than DOX was proved by the pathologic examination of main organs in our toxicity study.     

Nano-assemblies of J-aggregates based on a NIR dye as a multifunctional drug carrier for combination cancer therapy

The combination of chemotherapy with photothermal therapy, which may lead to improved therapeutic efficacies and reduced side effects of conventional chemotherapy, would require safe drug delivery systems (DDSs) with strong near-infrared (NIR) absorbance, efficient drug loading, and effective tumor homing ability. Herein, we fabricate nano-assemblies containing J-aggregates of a NIR dye, IR825, for drug delivery and combined photothermal & chemotherapy of cancer. It is found that IR825 could be complexed with a low-molecular-weight cationic polymer polyethylenimine (PEI), forming IR825@PEI J-aggregates with greatly enhanced NIR absorbance red-shifted to 915 nm. Those nano-assemblies of J-aggregates are further modified with polyethylene glycol (PEG), obtaining IR825@PEI-PEG nano-complex which exhibits great dispersity in physiological solutions, excellent photostability, and is able to efficiently load chemotherapeutic drug doxorubicin (DOX) via a unique strategy different from drug loading in conventional amphiphilic polymer-based DDSs. In vivo animal experiments uncover that IR825@PEI-PEG/DOX upon intravenous injection into tumor-bearing mice shows rather high tumor uptake as illustrated by photoacoustic imaging. In vivo combined photothermal & chemotherapy is then carried out, demonstrating great synergistic anti-tumor therapeutic effect remarkably superior to those achieved by the respective mono-therapies. Hence, we present a novel type of nanoscale DDSs based on nano-assemblies of small molecules without involving amphiphilic polymers, promising for imaging-guided combination cancer therapy.     

The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power

Photothermal therapy as a physical treatment approach to destruct cancer has emerged as an alternative of currently used cancer therapies. Previously we have shown that polyethylene glycol (PEG) functionalized nano-graphene oxide (nGO-PEG) with strong optical absorption in the near-infrared (NIR) region was a powerful photothermal agent for in vivo cancer treatment. In this work, by using ultra-small reduced graphene oxide (nRGO) with non-covalent PEG coating, we study how sizes and surface chemistry affect the in vivo behaviors of graphene, and remarkably improve the performance of graphene-based in vivo photothermal cancer treatment. Owing to the enhanced NIR absorbance and highly efficient tumor passive targeting of nRGO-PEG, excellent in vivo treatment efficacy with 100% of tumor elimination is observed after intravenous injection of nRGO-PEG and the followed 808 nm laser irradiation, the power density (0.15 W/cm², 5 min) of which is an order of magnitude lower than that usually applied for in vivo tumor ablation using many other nanomaterials. All mice after treatment survive over a period of 100 days without a single death or any obvious sign of side effect. Our results highlight that both surface chemistry and sizes are critical to the in vivo performance of graphene, and show the promise of using optimized nano-graphene for ultra-effective photothermal treatment, which may potentially be combined with other therapeutic approaches to assist our fight against cancer.     

An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment.     

A tumor-targeting near-infrared laser-triggered drug delivery system based on GO@Ag nanoparticles for chemo-photothermal therapy and X-ray imaging

In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and doxorubicin (DOX), one of the most effective drugs against a wide range of cancers, was employed as the model drug and linked to GO@Ag via ester bonds with a very high drug loading efficiency (∼82.0%, weight ratio of DOX/GO@Ag), then GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active tumor-targeting capacity and excellent stability in physiological solutions. The release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near-infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher antitumor efficacy without obvious toxic effects to normal organs owing to 8.4-fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR nanoparticles to combine the local specific chemotherapy with external photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag-DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.     

PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy

Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T₁-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy.     

Comparison of radiohaloanalogues of meta-iodobenzylguanidine (MIBG) for a combined gene- and targeted radiotherapy approach to bladder carcinoma

Targeted radiotherapy using radiolabelled meta-iodobenzylguanidine (MIBG) is a promising treatment option for bladder cancer, restricting the effects of radiotherapy to malignant cells thereby increasing efficacy and decreasing morbidity of radiotherapy. We investigated the efficacy of a combined gene therapy and targeted radiotherapy approach for bladder cancer using radiolabelled MIBG. The effectiveness of alternative radiohalogens and alternative preparations of radiolabelled MIBG for this therapeutic strategy were compared. Bladder cancer cells, EJ138, were transfected with a gene encoding the noradrenaline transporter (NAT) under the control of a tumour specific telomerase promoter, enabling them to actively take up radiolabelled MIBG. This resulted in tumour-specific cell kill. Uptake and retention of radioactivity in cells transfected with the NAT gene were compared with that obtained in cells transfected with the sodium iodide symporter (NIS) gene. Substantially greater uptake and longer retention of radioactivity in NAT-transfected cells was observed. Carrier-added (c.a.) [131I]MIBG, no-carrier added (n.c.a.) [131I]MIBG, and [211At]-labelled benzylguanidine (i.e. [211At] meta-astatobenzylguanidine (MABG)) were compared with respect to efficiency of induction of cell kill. N.c.a[(131)I]MIBG was more cytotoxic than c.a.[131I]MIBG. However, the alpha-emitter [211At]MABG was, by three orders of magnitude, more effective in causing tumour cell kill than the beta-emitter [131I]MIBG. We conclude that NAT gene transfer combined with the administration of n.c.a.[131I]MIBG or [211At]MABG, is a promising novel treatment approach for bladder cancer therapy.     

A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug

Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH₃)₂Cl₂(OH)₂]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment.     

Immunostimulatory oligonucleotides-loaded cationic graphene oxide with photothermally enhanced immunogenicity for photothermal/immune cancer therapy

Graphene oxide (GO) has attracted tremendous research interest due to its excellent electrical, thermal, and mechanical properties. Here, we apply the polyethylene glycol (PEG) and polyethylenimine (PEI) dual-polymer-functionalized GO (GO-PEG-PEI) as the carrier for efficient CpG delivery. GO-PEG-PEI can significantly promote the production of proinflammatory cytokines and enhance the immunostimulatory effect of CpG. In addition, the NIR optical absorbance of GO-PEG-PEI has been further applied to control the immunostimulatory activity of CpG ODNs, showing remarkably enhanced immunostimulation responses under NIR laser irradiation, owing to the photothermally induced local heating that accelerated intracellular trafficking of nanovectors. This is the first demonstration of using the photothermally enhanced intracellular transportation of nanocarriers for light-controllable CpG delivery. In vivo assay demonstrates that the GO-PEG-PEI-CpG complex provides synergistic photothermal and immunological effects under laser irradiation for cancer treatment, which shows the highest efficiency in tumor reduction, implying the excellent therapeutic efficacy of the GO-PEG-PEI-CpG complex in cancer therapy.     

Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods

Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention of GNR@DOX nanoparticles were attributed to their abilities to induce cellular apoptosis/necrosis and ablate intratumoral blood vessels. All these results suggested a considerable potential of GNR@DOX nanoplatform for treatment of metastatic breast cancer.     

FeS nanoplates as a multifunctional nano-theranostic for magnetic resonance imaging guided photothermal therapy

In this work, we develop magnetic iron sulfide (FeS) nanoplates as a theranostic agent for magnetic resonance (MR) imaging-guided photothermal therapy of cancer. FeS nanoplates are synthesized via a simple one-step method and then functionalized with polyethylene glycol (PEG). The obtained PEGylated FeS (FeS-PEG) nanoplates exhibit high NIR absorbance together with strong superparamagnetism. The r2 relaxivity of FeS-PEG nanoplates is determined to be 209.8 mm-1S-1, which appears to be much higher than that of iron oxide nanoparticles and several types of clinical approved T2-contrast agents. After intravenous (i.v.) injection, those nanoplates show high accumulation in the tumor as revealed by MR imaging. Highly effective photothermal ablation of tumors is then achieved in a mouse tumor model upon i.v. injection of FeS-PEG at a moderate dose (20 mg/kg) followed by 808-nm NIR laser irradiation. Importantly, it has been found that PEGylated FeS nanoplates after systemic administration could be gradually excreted from major organs of mice, and show no appreciable toxicity to the treated animals even at a dose (100 mg/kg) 5 times as high as that used for imaging & treatment. Our results demonstrate that PEGylated FeS nanoplates may be a promising class of theranostic nano-agents with a good potential for future clinical translation.     

Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal oral cancer therapies

Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient singlet oxygen generation when illuminated by 532 nm green light and high photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro experiments show that reactive oxygen species generated by green light and hyperthermia produced by NIR light constitute two different mechanisms for cancer cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing the uptake of RB by cancer cells. In vivo experiments are conducted on hamster cheek pouches to resemble the human oral cancer conditions more accurately to assess the therapeutic effectiveness. Compared to the single photodynamic therapy (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT capabilities provide better therapeutic effects against oral cancer and have large potential in cancer treatment.     

Folate-modified,indocyanine green-loaded lipid-polymer hybrid nanoparticles for targeted delivery of cisplatin

Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.     

Multifunctional PEG-GO/CuS nanocomposites for near-infrared chemo-photothermal therapy

The synergistic therapy, the combination of photothermal therapy and chemotherapy, has become a potential treatment in the battles with cancer. Here, we developed a synergistic therapy tool that based on CuS nanoparticles-decorated graphene oxide functionalized with polyethylene glycol (PEG-GO/CuS) for cervical cancer treatment. The as-synthesized PEG-GO/CuS nanocomposites with excellent biocompatibility was revealed to have high storage capacity for anticancer drug of doxorubicin (Dox) and high photothermal conversion efficiency, and were effectively employed for the ablation of tumor. In addition, the therapeutic efficacy of Dox-loaded PEG-GO/CuS (PEG-GO/CuS/Dox) nanocomposites was evaluated in vitro and in vivo for cervical cancer therapy. In vitro cell cytotoxicity tests of PEG-GO/CuS/Dox demonstrate about 1.3 and 2.7-fold toxicity than PEG-GO/CuS and free Dox under 5 min irradiation with NIR laser at 1.0 W/cm², owing to both PEG-GO/CuS-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, mouse cervical tumor growth was found to be significantly inhibited by the chemo-photothermal effect of PEG-GO/CuS/Dox nanocomposites, resulting in effective tumor reduction. Overall, compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrates better therapeutic efficacy of cancer in vitro and in vivo. These findings highlight the promise of the highly versatile multifunctional nanoparticles in biomedical application.     

A multi-stimuli responsive gold nanocage–hyaluronic platform for targeted photothermal and chemotherapy

Noninvasive and pinpointed intracellular drug release that responds to multiple stimulus is still a formidable challenge for cancer therapy. Herein, we reported a multi-stimuli responsive platform based on drug loaded gold nanocages @ hyaluronic acid (AuNCs-HA) for pinpointed intracellular drug release. These well-prepared nanohybrids could specifically recognize cancer cells via HA-CD44 interactions and be efficiently endocytosed by receptor-mediated process. Subsequently, the coated HA molecules could be degraded in lysosomes, resulting in the release of encapsulated drug. In addition, by taking advantage of the excellent photothermal properties, the AuNCs could accelerate the release of encapsulated drug and induce a higher therapeutic efficacy upon near-infrared (NIR) irradiation. In vitro results confirmed that the encapsulated drug could only be pinpointedly released in intracellular environments, which permitted high therapeutic efficacy against cancer cells and minimized the side effects. Importantly, as compared to that of the two therapies independently, a complete inhibition of tumor growth treated with the combination of chemotherapy and photothermal therapy was observed in vivo. Taken together, our present study provides new insights into developing pinpointed, multi-stimuli responsive intracellular drug release systems for synergistic cancer therapy.     

A fullerene-based multi-functional nanoplatform for cancer theranostic applications

Recently, nanomaterials with multiple functions, such as drug carrier, MRI and optical imaging, photothermal therapy etc, have become more and more popular in the domain of cancer research. In this study, a C60–IONP nanocomposite is synthesized via decorating iron oxide nanoparticles (IONP) onto fullerene (C60) and then functionalized by polyethylene glycol (PEG2000), giving C60–IONP–PEG with excellent stability in physiological solutions, finally folic acid (FA), a widely used tumor targeting molecule, was linked to C60–IONP–PEG in order to obtain an active tumor targeting effect to MCF-7 cells and malignant tumor in mice models. Herein, a hybrid nanoplatform with multi-functional characteristics for cancer diagnosis, photodynamic therapy (PDT), radiofrequency (RF) thermal therapy (RTT) and magnetic targeting applications was developed and explored its biofunctions in vitro and in vivo. C60–IONP–PEG–FA showed neglectable toxicity, not only served as a powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agent, but also as a strong photosensitizer and powerful agent for photothermal ablation of tumor, furthermore a remarkable synergistic enhancement of PDT combination with RTT was also observed during the treatment both in vitro and in vivo. Moreover, the multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent active tumor targeting and magnetic targeted abilities. This work showed the multi-functional C60–IONP–PEG–FA nanoplatform had a great potential for cancer theranostic applications.     

Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy

In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm² for 5 min (or 0.5 W/cm² for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.     

Dual functional AuNRs@MnMEIOs nanoclusters for magnetic resonance imaging and photothermal therapy

A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T₂-weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r₂ relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were – 70.4 ± 4.3% versus – 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy.     

Activation of inflammasomes by tumor cell death mediated by gold nanoshells

Gold nanoshell-enabled photothermal therapy (NEPTT) utilizes the efficient thermal conversion of near infrared (NIR) light for the ablation of cancer cells. Cancer therapies that combine cell killing with the induction of a strong immune response against the dying tumor cells have been shown to increase therapeutic efficacy in the clearance and regression of cancers. In this study, we assessed the ability of dying cells generated by in vitro NEPTT to activate inflammasome complexes. We quantified levels of major danger-associated molecular patterns (DAMPs), including adenosine triphosphate (ATP), adenosine diphosphate (ADP), and uric acid, released from tumor cells treated by NEPTT. The amount of DAMPs released was dependent on the dose of nanoshells internalized by cells. However, under all the employed conditions, the levels of generated DAMPs were insufficient to activate inflammasome complexes and to induce the production of pro-inflammatory cytokines (i.e. IL-1β). The results from this study provide insights into the development of nanoplasmonics for combining both photothermal therapy and immunotherapy to eradicate cancers.     

Two-dimensional magnetic WS2@Fe3O4 nanocomposite with mesoporous silica coating for drug delivery and imaging-guided therapy of cancer

Integrating multiple imaging and therapy functionalities into one single nanoscale platform has been proposed to be a promising strategy in cancer theranostics. In this work, WS₂ nanosheets with their surface pre-adsorbed with iron oxide (IO) nanoparticles via self-assembly are coated with a mesoporous silica shell, on to which polyethylene glycol (PEG) is attached. The obtained WS₂-IO@MS-PEG composite nanoparticles exhibit many interesting inherent physical properties, including high near-infrared (NIR) light and X-ray absorbance, as well as strong superparamagnetism. In the mean time, the mesoporous silica shell in WS₂-IO@MS-PEG could be loaded with a chemotherapy drug, doxorubicin (DOX), whose intracellular release afterwards may be triggered by NIR-induced photothermal heating for enhanced cancer cell killing. Upon systemic administration of such drug-loaded nano-theranostics, efficient tumor homing of WS₂-IO@MS-PEG/DOX is observed in tumor-bearing mice as revealed by three-modal fluorescence, magnetic resonance (MR), and X-ray computed tomography (CT) imaging. In vivo combined photothermal & chemotherapy is then carried out with WS₂-IO@MS-PEG/DOX, achieving a remarkably synergistic therapeutic effect superior to the respective mono-therapies. Our study highlights the promise of developing multifunctional nanoscale theranostics based on two-dimensional transition metal dichalcogenides (TMDCs) such as WS₂ for multimodal imaging-guided combination therapy of cancer.