A Lactate-Depleting metal organic framework-based nanocatalyst reinforces intratumoral T cell response to boost anti-PD1 immunotherapy.

Infiltration and activation of intratumoral T lymphocytes are critical for immune checkpoint blockade (ICB) therapy. Unfortunately, the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) induced by tumor metabolic reprogramming cooperatively hinder the ICB efficacy. Herein, we engineered a lactate-depleting MOF-based catalytic nanoplatform (LOX@ZIF-8@MPN), encapsulating lactate oxidase (LOX) within zeolitic imidazolate framework-8 (ZIF-8) coupled with a coating of metal polyphenol network (MPN) to reinforce T cell response based on a "two birds with one stone" strategy. LOX could catalyze the degradation of the immunosuppressive lactate to promote vascular normalization, facilitating T cell infiltration. On the other hand, hydrogen peroxide (H2O2) produced during lactate depletion can be transformed into anti-tumor hydroxyl radical (•OH) by the autocatalytic MPN-based Fenton nanosystem to trigger immunogenic cell death (ICD), which largely improved the tumor immunogenicity. The combination of ICD and vascular normalization presents a better synergistic immunopotentiation with anti-PD1, inducing robust anti-tumor immunity in primary tumors and recurrent malignancies. Collectively, our results demonstrate that the concurrent depletion of lactate to reverse the immunosuppressive TME and utilization of the by-product from lactate degradation via cascade catalysis promotes T cell response and thus improves the effectiveness of ICB therapy.

An Immunocompetent Hafnium Oxide-Based STING Nanoagonist for Cancer Radio-immunotherapy.

cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.

Nanointegrative In Situ Reprogramming of Tumor-Intrinsic Lipid Droplet Biogenesis for Low-Dose Radiation-Activated Ferroptosis Immunotherapy.

Low-dose radiotherapy (LDR) has shown significant implications for inflaming the immunosuppressive tumor microenvironment (TME). Surprisingly, we identify that FABP-dependent lipid droplet biogenesis in tumor cells is a key determinant of LDR-evoked cytotoxic and immunostimulatory effects and developed a nanointegrated strategy to promote the antitumor efficacy of LDR through cooperative ferroptosis immunotherapy. Specifically, TCPP-TK-PEG-PAMAM-FA, a nanoscale multicomponent functional polymer with self-assembly capability, was synthesized for cooperatively entrapping hafnium ions (Hf4+) and HIF-1α-inhibiting siRNAs (siHIF-1α). The TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α nanoassemblies are specifically taken in by folate receptor-overexpressing tumor cells and activated by the elevated cellular ROS stress. siHIF-1α could readily inhibit the FABP3/7 expression in tumor cells via HIF-1α-FABP3/7 signaling and abolish lipid droplet biogenesis for enhancing the peroxidation susceptibility of membrane lipids, which synergizes with the elevated ROS stress in the context of Hf4+-enhanced radiation exposure and evokes pronounced ferroptotic damage in vital membrane structures. Interestingly, TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α-enhanced ferroptotic biomembrane damage also facilitates the exposure of tumor-associated antigens (TAAs) to promote post-LDR immunotherapeutic effects, leading to robust tumor regression in vivo. This study offers a nanointegrative approach to boost the antitumor effects of LDR through the utilization of tumor-intrinsic lipid metabolism.

Injectable microenvironment-responsive hydrogels with redox-activatable supramolecular prodrugs mediate ferroptosis-immunotherapy for postoperative tumor treatment.

Immunotherapy is an emerging antitumor modality with high specificity and persistence, but its application for resected tumor treatment is impeded by the low availability of tumor-specific antigens and strong immunosuppression in the wound margin. Here a nanoengineered hydrogel is developed for eliciting robust cooperative ferroptosis-immunotherapeutic effect on resected tumors. Specifically, ß-cyclodextrin (ß-CD) is first grafted onto oxidized sodium alginate (OSA) through Schiff base ligation, which could trap cRGD-modified redox-responsive Withaferin prodrugs (WA-cRGD) to obtain the hydrogel building blocks (Gel@WA-cRGD). Under Ca2+-mediated crosslinking, Gel@WA-cRGD rapidly forms physiologically stable hydrogels, of which the porous network is used to deliver programmed cell death ligand 1 antibodies (aPD-L1). After injection into the post-surgical wound cavity, the ß-CD-entrapped WA-cRGD is detached by the local acidity and specifically internalized by residual tumor cells to trigger ferroptosis, thus releasing abundant damage-associated molecular patterns (DAMPs) and tumor-derived antigens for activating the antigen-presenting cell-mediated cross-presentation and downstream cytotoxic T cell (CTL)-mediated antitumor responses. Furthermore, aPD-L1 could block PD-1/PD-L1 interaction and enhance the effector function of CTLs to overcome tumor cell-mediated immunosuppression. This cooperative hydrogel-based antitumor strategy for ferroptosis-immunotherapy may serve as a generally-applicable approach for postoperative tumor management. STATEMENT OF SIGNIFICANCE: To overcome the immunosuppressive microenvironment in resected solid tumors for enhanced patient survival, here we report a nanoengineered hydrogel incorporated supramolecular redox-activatable Withaferin prodrug and PD-L1 antibody, which could elicit robust cooperative ferroptosis-immunotherapeutic effect against residual tumor cells in the surgical bed to prevent tumor relapse, thus offering a generally-applicable approach for postoperative tumor management.

A MOF-Based Potent Ferroptosis Inducer for Enhanced Radiotherapy of Triple Negative Breast Cancer.

Radiotherapy (RT) is one of the important clinical treatments for local control of triple-negative breast cancer (TNBC), but radioresistance still exists. Ferroptosis has been recognized as a natural barrier for cancer progression and represents a significant role of RT-mediated anticancer effects, while the simultaneous activation of ferroptosis defensive system during RT limits the synergistic effect between RT and ferroptosis. Herein, we engineered a tumor microenvironment (TME) degradable nanohybrid with a dual radiosensitization manner to combine ferroptosis induction and high-Z effect based on metal-organic frameworks for ferroptosis-augmented RT of TNBC. The encapsulated l-buthionine-sulfoximine (BSO) could inhibit glutathione (GSH) biosynthesis for glutathione peroxidase 4 (GPX4) inactivation to break down the ferroptosis defensive system, and the delivered ferrous ions could act as a powerful ferroptosis executor via triggering the Fenton reaction; the combination of them induces potent ferroptosis, which could synergize with the surface decorated Gold (Au) NPs-mediated radiosensitization to improve RT efficacy. In vivo antitumor results revealed that the nanohybrid could significantly improve the therapeutic efficacy and antimetastasis efficiency based on the combinational mechanism between ferroptosis and RT. This work thus demonstrated that combining RT with efficient ferroptosis induction through nanotechnology was a feasible and promising strategy for TNBC treatment.

Harnessing Hafnium-Based Nanomaterials for Cancer Diagnosis and Therapy.

With the rapid development of nanotechnology and nanomedicine, there are great interests in employing nanomaterials to improve the efficiency of disease diagnosis and treatment. The clinical translation of hafnium oxide (HfO2 ), commercially namedas NBTXR3, as a new kind of nanoradiosensitizer for radiotherapy (RT) of cancers has aroused extensive interest in researches on Hf-based nanomaterials for biomedical application. In the past 20 years, Hf-based nanomaterials have emerged as potential and important nanomedicine for computed tomography (CT)-involved bioimaging and RT-associated cancer treatment due to their excellent electronic structures and intrinsic physiochemical properties. In this review, a bibliometric analysis method is employed to summarize the progress on the synthesis technology of various Hf-based nanomaterials, including HfO2 , HfO2 -based compounds, and Hf-organic ligand coordination hybrids, such as metal-organic frameworks or nanoscaled coordination polymers. Moreover, current states in the application of Hf-based CT-involved contrasts for tissue imaging or cancer diagnosis are reviewed in detail. Importantly, the recent advances in Hf-based nanomaterials-mediated radiosensitization and synergistic RT with other current mainstream treatments are also generalized. Finally, current challenges and future perspectives of Hf-based nanomaterials with a view to maximize their great potential in the research of translational medicine are also discussed.

Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy.

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

Effect of ligating dogs' arteries and veins on femoral heads.

BACKGROUND: We separately ligated the arteries and veins of dogs to establish a canine femoral head necrosis model, then compared the differences between the outcomes of the two ligation methods on canine femoral heads. METHODS: Twenty-four dogs in this experiment were randomly and evenly sorted into two groups (Group A, the arterial group; and Group B, the venous group). In dogs in Group A, the unilateral deep femoral arteries of the hips were ligated. In dogs in Group B, the unilateral deep femoral veins of the hips were ligated. Two dogs from each group were randomly selected at the 2nd, 4th, 6th, 8th, 10th, and 12th weeks postoperatively and were marked as Groups A1-A6 and B1-B6 according to the selection times. The dogs underwent X-ray (DR) and a magnetic resonance imaging (MRI) plain scan (1.5 T) on both hip joints and were then sacrificed. Bilateral femoral head specimens were soaked in formalin and then decalcified. Hematoxylin-eosin (HE) staining and histopathologic evaluation were performed on the tissue sections. RESULTS: In dogs in Group B, abnormal pathologic changes, such as adipocytes fusing into cysts, were observed at the 4th week after establishing the model. MRI scans showed abnormal signal intensity at the 6th week, and fibrocyte regrowth was demonstrated in the necrotic area of the femoral heads at the 10th week. At the same time, indicators of tissue repair and fresh granulation tissue emerged. Changes in dogs in Group A, such as interstitial haemorrhage and oedema, were not noted in pathologic sections until 6 weeks after the model was established. MRI showed abnormal signals, such as a linear low signal intensity in the weight-bearing area of the femoral heads at the 8th week. New blood vessels emerged in the necrotic area at the 12th week, while there was no proliferation of fibrocytes and tissues. CONCLUSIONS: The development and evolution of femoral head necrosis caused by ligation of the main veins of the femoral head in dogs appeared earlier than in dogs with arterial ligation, and pathologic changes, such as necrosis and repair, were more significant in dogs in the venous group than in dogs in the other group.

Tumor-Tropic Adipose-Derived Mesenchymal Stromal Cell Mediated Bi2 Se3 Nano-Radiosensitizers Delivery for Targeted Radiotherapy of Non-Small Cell Lung Cancer.

With the successful marriage between nanotechnology and oncology, various high-Z element containing nanoparticles (NPs) are approved as radiosensitizers to overcome radiation resistance for enhanced radiotherapy (RT). Unfortunately, NPs themselves lack specificity to tumors. Due to the inherent tropism nature of malignant cells, mesenchymal stem cells (MSCs) emerge as cell-mediated delivery vehicles for functional NPs to improve their therapeutic index. Herein, radiosensitive bismuth selenide (Bi2 Se3 ) NPs-laden adipose-derived mesenchymal stromal cells (AD-MSCs/Bi2 Se3 ) are engineered for targeted RT of non-small cell lung cancer (NSCLC). The results reveal that the optimized intracellular loading strategy hardly affects cell viability, specific surface markers, or migration capability of AD-MSCs, and Bi2 Se3  NPs can be efficiently transported from AD-MSCs to tumor cells. In vivo biodistribution test shows that the Bi2 Se3 NPs accumulation in tumor is increased 20 times via AD-MSCs-mediated delivery. Therefore, AD-MSCs/Bi2 Se3 administration synchronized with X-ray irradiation controls the tumor progress well in orthotopic A549 tumor bearing mice. Considering that MSCs migrate better to irradiated tumor cells in comparison to nonirradiated ones and MSCs preferentially accumulate within lung tissues after systemic administration into accounts, the tumor-tropic MSCs/NPs system is feasible and promising for targeted RT treatment of NSCLC.

Anti-VEGFR2-labeled enzyme-immobilized metal-organic frameworks for tumor vasculature targeted catalytic therapy.

Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction with enzyme glucose oxidase (GOD) modified on Fe-based metal organic framework (Fe-MOF) coupled with anti-VEGFR2.The GOD enzyme could catalyze the intratumoral glucose decomposition to trigger tumor starvation and yet provide abundant hydrogen peroxide as the substrate for Fenton-like reaction catalyzed by Fe-MOF to produce sufficient highly toxic hydroxyl radicals for enhanced chemodynamic therapy and instantly attacked tumor vascular endothelial cells to destroy the existing vasculature, while the anti-VEGFR2 antibody guided the nanohybrids to target blood vessels and block the VEGF-VEGFR2 connection to prevent angiogenesis. Both in vitro and in vivo results demonstrated the smart nanohybrids could cause the tumor cell apoptosis and vasculature disruption, and exhibited enhanced tumor regression in A549 xenograft tumor-bearing mice model. This study suggested that synergistic targeting tumor growth and its vasculature network would be more promising for curing solid tumors. STATEMENT OF SIGNIFICANCE: Cooperative destruction of tumor cells and tumor vasculature offers a potential avenue for cancer therapy. Under this premise, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and new angiogenesis inhibition was developed through a cascade reaction with glucose oxidase modified on the surface of iron-based metal organic framework coupled with VEGFR2 antibody. The resulting data demonstrated that a therapeutic regimen targeting tumor growth as well as its vasculature with both existing vasculature disruption and neovasculature inhibition would be more potential for complete eradication of tumors.

Reeducating Tumor-Associated Macrophages Using CpG@Au Nanocomposites to Modulate Immunosuppressive Microenvironment for Improved Radio-Immunotherapy.

With the recent success of immune checkpoint blockade (ICB) in cancer immunotherapy, there has been renewed interest in evaluating the combination of ICB inhibitors with radiotherapy (RT) in clinical trials in view of the localized RT-initiated vaccination effect, which can be augmented further by systemic immune-stimulating agents. Unfortunately, traditional RT/ICB accompanies severe toxicity from high-dose ionizing irradiation and low response rate from RT-aggravated immunosuppression, among which M2-type tumor-associated macrophages (TAMs) play an important role. Herein, CpG-decorated gold (Au) nanoparticles (CpG@Au NPs) were fabricated to improve the RT/ICB efficacy by immune modulation under low-dose X-ray exposure, where Au NPs served as radioenhancers to minimize the radiotoxicity, and yet acted as nanocarriers to deliver CpG, a toll-like receptor 9 agonist, to re-educate immunosuppressive M2 TAMs to immunostimulatory M1 counterparts, thus arousing innate immunity and meanwhile priming T cell activation. When combined with an anti-programmed death 1 antibody, irradiated CpG@Au led to consistent abscopal responses that efficiently suppressed distant tumors in a bilateral GL261 tumor-bearing model. This work thus demonstrates that CpG@Au-mediated macrophage reeducation could efficiently modulate the tumor-immune microenvironment for synergistic RT/ICB.

Metal-ligand coordination nanomaterials for radiotherapy: emerging synergistic cancer therapy.

Radiotherapy (RT) plays a central role in curing malignant tumors. However, the treatment outcome is often impeded by low radiation absorption coefficients and radiation resistance of tumors along with normal tissue radio-toxicity. With the development of nanotechnology, nanomaterials in combination with RT offer the possibility to improve the therapeutic efficacy yet reduce side-effects. Metal-ligand coordination nanomaterials, including nanoscale metal-organic frameworks (NMOFs) and nanoscale coordination polymers (NCPs), formed by coordination interactions between inorganic metal ions/clusters with organic bridging ligands, have shown great potential in the field of radiation oncology in recent years in view of their unique advantages including the porous structure, high surface area, periodic frameworks, and diverse selections of both metal ions/clusters and organic ligands. In this review, we summarize the recent advances in NMOF/NCP-mediated synergistic RT in combination with hypoxia relief, chemotherapy, photodynamic therapy, photothermal therapy, chemodynamic therapy or immunotherapy, which emerged in the last 3 years, and describe cooperative enhancement interactions among these synergistic combinations. Moreover, the potential challenges and future prospects of this rapidly growing direction were also addressed.

Nanoscaled Metal-Organic Frameworks for Biosensing, Imaging, and Cancer Therapy.

Owing to the progressive development of metal-organic frameworks (MOFs) synthetic processes and their unique characters associated with the excellent performance-selectable composition, tunable pore scale, large surface area, and good thermal stability, MOFs have captured the interest and the imagination of an increasing number of scientists working in different fields. In the area of biomedical applications, MOFs are especially involved in sensing, molecular imaging, and drug delivery, with strong contributions to the whole nanomedicine area. Recently, these materials have been scaled down to nanometer sizes with the advancement of chemical synthesis gradually reaching an adjustable level. This review mainly discusses and summarizes the general synthesis, properties, and biomedical applications of nanoscaled MOFs and their composites in biosensing, imaging, and cancer therapy within the latest three years. The remaining challenges and future opportunities in this field, in terms of processing techniques, maximizing composite properties, and prospects for clinical applications, are also indicated.

Therapeutic Nanoparticles Based on Curcumin and Bamboo Charcoal Nanoparticles for Chemo-Photothermal Synergistic Treatment of Cancer and Radioprotection of Normal Cells.

Low water solubility, extensive metabolism, and drug resistance are the existing unavoidable disadvantages of the insoluble drug curcumin in biomedical applications. Herein, we employed d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-functionalized near-infrared (NIR)-triggered photothermal mesoporous nanocarriers with bamboo charcoal nanoparticles (TPGS-BCNPs) to load and deliver curcumin for improving its bioavailability. This system could considerably increase the accumulation of curcumin in cancer cells for enhanced curcumin bioavailability via simultaneously promoting the cellular internalization of the as-synthesized composite (TPGS-BCNPs@curcumin) by the size effect of NPs and considerably triggering controlled curcumin release from TPGS-BCNPs@curcumin by NIR stimulation and reducing efflux of curcumin by the P-glycoprotein (P-gp) inhibition of TPGS, so as to enhance the therapeutic effect of curcumin and realize a better chemo-photothermal synergetic therapy in vitro and in vivo. Besides cancer therapy, studies indicated that curcumin and some carbon materials could be used as radical scavengers that play an important role in the radioprotection of normal cells. Hence, we also investigated the free-radical-scavenging ability of the TPGS-BCNPs@curcumin composite in vitro to preliminarily evaluate its radioprotection ability for healthy tissues. Therefore, our work provides a multifunctional delivery system for curcumin bioavailability enhancement, chemo-photothermal synergetic therapy of cancer, and radioprotection of healthy tissues.

Near infrared light triggered nitric oxide releasing platform based on upconversion nanoparticles for synergistic therapy of cancer stem-like cells.

Near infrared (NIR) light-driven nitric oxide (NO) release nano-platform based on upconversion nanoparticles (UCNPs) and light sensitive NO precursor Roussin's black salt (RBS) was fabricated to generate NO upon 808nm irradiation. The application of 808nm laser as the excitation source could achieve better penetration depth and avoid overheating problem. The combination of UCNPs and RBS could realize the on-demand release of NO at desired time and location by simply controlling the output of NIR laser. Cellular uptake results showed that more nanoparticles were internalized in cancer stem-like cells (CSCs) rather than non-CSCs. Therefore, a synergistic cancer therapy strategy to eradicate both CSCs and non-CSCs simultaneously was developed. Traditional chemo-drug could inhibit non-CSCs but has low killing efficiency in CSCs. However, we found that the combination of NO and chemotherapy could efficiently inhibit CSCs in bulk cells, including inhibiting mammosphere formation ability, decreasing CD44+/CD24- subpopulation and reducing tumorigenic ability. The mechanism studies confirmed that NO could not only induce apoptosis but also increase drug sensitivity by declining drug efflux in CSCs. This UCNPs-based platform may provide a new combinatorial strategy of NO and chemotherapy to improve cancer treatment.

Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed.

Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging.

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat and Fe3O4 NPs served as target moiety directed by external magnetic field to tumor site. The MoS2/Fe3O4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method. And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo. Specifically, the MSIOs can be applied as a dual-modal probe for T2-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption. Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer. All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.

Bismuth sulfide nanorods as a precision nanomedicine for in vivo multimodal imaging-guided photothermal therapy of tumor.

Here, we present a precision cancer nanomedicine based on Bi(2)S(3) nanorods (NRs) designed specifically for multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)-guided photothermal therapy (PTT). The as-prepared Bi(2)S(3) NRs possess ideal photothermal effect and contrast enhancement in MSOT/CT bimodal imaging. These features make them simultaneously act as "satellite" and "precision targeted weapon" for the visual guide to destruction of tumors in vivo, realizing effective tumor destruction and metastasis inhibition after intravenous injection. In addition, toxicity screening confirms that Bi(2)S(3) NRs have well biocompatibility. This triple-modality-nanoparticle approach enables simultaneously precise cancer therapy and therapeutic monitoring.

TPGS-stabilized NaYbF4:Er upconversion nanoparticles for dual-modal fluorescent/CT imaging and anticancer drug delivery to overcome multi-drug resistance.

Multi-drug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively investigated for overcoming MDR in cancer therapy because of its ability to inhibit P-glycoprotein (P-gp). In this work, TPGS was for the first time used as a new surface modifier to functionalize NaYbF4:Er upconversion nanoparticles (UNCPs) and endowed the as-prepared products (TPGS-UCNPs) with excellent water-solubility, P-gp inhibition capability and imaging-guided drug delivery property. After the chemotherapeutic drug (doxorubicin, DOX) loading, the as-formed composites (TPGS-UCNPs-DOX) exhibited potent killing ability for DOX-resistant MCF-7 cells. Flow-cytometric assessment and Western blot assay showed that the TPGS-UCNPs could potently decrease the P-gp expression and facilitate the intracellular drug accumulation, thus achieving MDR reversal. Moreover, considering that UCNPs process efficient upconversion emission and Yb element contained in UCNPs has strong X-ray attenuation ability, the as-obtained composite could also serve as a dual-modal probe for upconversion luminescence (UCL) imaging and X-ray computed tomography (CT) imaging, making them promising for imaging-guided cancer therapy.