Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer.

Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.

A two-stage exacerbated hypoxia nanoengineering strategy induced amplifying activation of tirapazamine for microwave hyperthermia-chemotherapy of breast cancer.

Microwave hyperthermia (MH) is an emerging treatment for solid tumors, such as breast cancer, due to its advantages of minimally invasive and deep tissue penetration. However, MH induced tumor hypoxia is still an obstacle to breast tumor treatment failure. Therefore, an original nanoengineering strategy was proposed to exacerbate hypoxia in two stages, thereby amplifying the efficiency of activating tirapazamine (TPZ). And a novel microwave-sensitized nanomaterial (GdEuMOF@TPZ, GEMT) is designed. GdEuMOF (GEM) nanoparticles are certified excellent microwave (MW) sensitization performance, thus improving tumor selectivity to achieve MH. Meanwhile MW can aggravate the generation of thrombus and caused local circulatory disturbance of tumor, resulting in the Stage I exacerbated hypoxia environment passively. Due to tumor heterogeneity and uneven hypoxia, GEMT nanoparticles under microwave could actively deplete residual oxygen through the chemical reaction, exacerbating hypoxia level more evenly, thus forming the Stage II of exacerbated hypoxia environment. Consequently, a two-stage exacerbated hypoxia GEMT nanoparticles realize amplifying activation of TPZ, significantly enhance the efficacy of microwave hyperthermia and chemotherapy, and effectively inhibit breast cancer. This research provides insights into the development of progressive nanoengineering strategies for effective breast tumor therapy.

Prepared MW-Immunosensitizers Precisely Release NO to Downregulate HIF-1α Expression and Enhance Immunogenic Cell Death.

Microwave thermotherapy (MWTT) has limited its application in the clinic due to its high rate of metastasis and recurrence after treatment. Nitric oxide (NO) is a gaseous molecule that can address the high metastasis and recurrence rates after MWTT by increasing thermal sensitivity, down-regulating the expression of hypoxia-inducible factor-1 (HIF-1), and inducing the immunogenic cell death (ICD). Therefore, GaMOF-Arg is designed, a gallium-based organic skeleton material derivative loaded with L-arginine (L-Arg), and coupled the mitochondria-targeting drug of triphenylphosphine (TPP) on its surface to obtain GaMOF-Arg-TPP (GAT) MW-immunosensitizers. When GAT MW-immunosensitizers are introduced into mice through the tail vein, reactive oxygen species (ROS) are generated and L-Arg is released under MW action. Then, L-Arg reacts with ROS to generate NO, which not only downregulates HIF-1 expression to improve tumor hypoxia exacerbated by MW, but also enhances immune responses by augment calreticulin (CRT) exposure, high mobility group box 1 (HMGB1) release, and T-cell proliferation to achieve prevention of tumor metastasis and recurrence. In addition, NO can induce mitochondria damage to increase their sensitivity to MWTT. This study provides a unique insight into the use of metal-organic framework MW-immunosensitizers to enhance tumor therapy and offers a new way to treat cancer efficiently.

Programmed Upregulation of HSP70 by Metal-Organic Frameworks Nanoamplifier for Enhanced Microwave Thermal-Immunotherapy.

Thermotherapy can directly kill tumor cells whilst being accompanied by immune-enhancing effects. However, this immune-enhancing effect suffers from insufficient expression of immune response factors (e.g., heat shock protein 70, HSP70), resulting in no patient benefiting due to the recurrence of tumor cells after thermotherapy. Herein, a nanoengineered strategy of programmed upregulating of the immune response factors for amplifying synergistic therapy is explored. Metal-organic frameworks nanoamplifiers (teprenone/nitrocysteine@ZrMOF-NH2 @L-menthol@triphenylphosphine, GGA/CSNO@ZrMOF-NH2 -LM-TPP nanoamplifier, and GCZMT nanoamplifier) achieve excellent microwave (MW) thermal-immunotherapy by programmed induction of HSP70 expression. After intravenous administration, GCZMT nanoamplifiers target the mitochondria, and then release nitric oxide (NO) under MW irradiation. NO inhibits the growth of tumor cells by interfering with the energy supply of cells. Subsequently, under the combination of MW, NO, and GGA, HSP70 expression can be programmed upregulated, which can induce the response of cytotoxic CD4+ T cells and CD8+ T cells, and effectively activate antitumor immunotherapy. Hence, GCZMT nanoamplifier-mediated MW therapy can achieve a satisfactory therapeutic effect with the tumor inhibition of 97%. This research offers a distinctive insight into the exploitation of metal-organic frameworks nanoamplifiers for enhanced tumor therapy, which provides a new approach for highly effective cancer treatment.

A multifunctional nanoplatform for improving microwave hyperthermia by a combination therapy of vessel disruptive agent and immune modulator.

Microwave (MW) hyperthermia is one of the safest and most efficient minimally invasive tumor treatment methods, it is restricted by the bottlenecks of the heat sink effect and ineffective immune activation. Herein, a multifunctional nano platform with the load of nano immune modulator bimetallic metal-organic framework (BM), tumor vessel destructive agent and prodrug for gas production is developed for improving MW hyperthermia. Specifically, the combretastatin A4 phosphate (CA4P) was a vessel destructive agent to reduce MW heat loss by destructing the tumor blood vessel. Moreover, the as designed BM can scavenge the endogenic reactive oxygen species, which is conducive to hydrogen sulfide gas (H2S) that produced by bismuth sulfide (Bi2S3) to activate immune cells. Our in vivo experimental results demonstrate the destruction of tumor blood vessels coupled with the activated immune system results in the remarkable antitumor effect. This study provides an efficient strategy to improve MW hyperthermia by a combination of vasculature-targeting therapy with systemic immunity.

Enhanced Photothermal-Photodynamic Therapy by Indocyanine Green and Curcumin-Loaded Layered MoS2 Hollow Spheres via Inhibition of P-Glycoprotein.

PURPOSE: P-glycoprotein (P-gp), which is highly expressed in liver cancer cells, is one of the obstacles for the treatment of cancer. In this study, we have prepared and characterized a kind of novel ICG&Cur@MoS2 (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely. METHODS: In this work, plenty of studies including drug release, acute toxicity, Western blot, real-time PCR, cell viability, therapeutic experiment in vivo, immunofluorescence and so on were conducted to test the antitumor potential of ICG&Cur@MoS2 and the inhibitory effect of curcumin on P-gp. RESULTS: The ICG&Cur@MoS2 NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS2 + NIR group was significantly lower than that in ICG@MoS2 + NIR group (75.3% vs 81.2%, 59.0% vs 64.4%, 20.3% vs 27.5%, and 15.4% vs 22.3%) at the concentration of ICG at 0.5, 5, 25, 50 µg/mL (P<0.05 at each concentration). Western blot, Q-PCR, and immunofluorescence assay indicate ICG&Cur@MoS2 NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS2 + NIR group are significantly smaller than those in the MoS2 + NIR group (95.0 vs 420.9 mm3, p<0.05). CONCLUSION: In conclusion, we have successfully synthesized ICG&Cur@MoS2 nanoparticles which can not only achieve PTT-PDT but also inhibit P-gp effectively. Our findings indicate that the PTT-PDT exhibits great potential in the treatment of hepatocellular carcinoma. Meanwhile, ICG&Cur@MoS2 can effectively inhibit the expression of P-gp, which will enhance the PDT effect.

Tumor reoxygenation for enhanced combination of radiation therapy and microwave thermal therapy using oxygen generation in situ by CuO nanosuperparticles under microwave irradiation.

As known, radiation therapy (RT) can exacerbate the degree of hypoxia of tumor cells, which induces serious resistance to RT and in turn, is the greatest obstacle to RT. Reoxygenation can restore the hypoxic state of tumor cells, which plays an important role in reshaping tumor microenviroment for achieving optimal therapeutic efficacy. Herein, we report for the first time that microwave (MW)-triggered IL-Quercetin-CuO-SiO2@ZrO2-PEG nanosuperparticles (IQuCS@Zr-PEG NSPs) have been used to achieve an optimal RT therapeutic outcomes by the strategy of upregulating tumor reoxygenation, i.e. hypoxic cells acquire oxygen and return to normal state. Methods: We prepared a promising multifunctional nanosuperparticle to upregulate tumor reoxygenation by utilizing CuO nanoparticle to generate oxygen under MW irradiation in the tumor microenvironment. The IQuCS@Zr-PEG NSPs were obtained by introducing CuO nanoparticles, MW sensitizer of 1-butyl-3-methylimidazolium hexafluorophosphate (IL), radiosensitizer of Quercetin (Qu) and surface modifier of monomethoxy polyethylene glycol sulfhyl (mPEG-SH, 5k Da) into mesoporous sandwich SiO2@ZrO2 nanosuperparticles (SiO2@ZrO2 NSPs). The release oxygen by IQuCS@Zr-PEG NSPs under MW irradiation was investigated by a microcomputer dissolved oxygen-biochemical oxygen demand detector (DO-BOD) test. Finally, we used the 99mTc-HL91 labeled reoxygenation imaging, Cellular immunofluorescence, immunohistochemistry, and TUNEL experiments to verify that this unique MW-responsive reoxygenation enhancer can be used to stimulate reshaping of the tumor microenvironment. Results: Through experiments we found that the IQuCS@Zr-PEG NSPs can persistently release oxygen under the MW irradiation, which upregulates tumor reoxygenation and improve the combined tumor treatment effect of RT and microwave thermal therapy (MWTT). Cellular immunofluorescence and immunohistochemistry experiments demonstrated that the IQuCS@Zr-PEG NSPs can downregulate the expression of hypoxia-inducible factor 1α (HIF-1α) under MW irradiation. The 99mTc-HL91 labeled reoxygenation imaging experiment also showed that the oxygen generated by IQuCS@Zr-PEG NSPs under MW irradiation can significantly increase the reoxygenation capacity of tumor cells, thus reshaping the tumor microenvironment. The high inhibition rate of 98.62% was achieved in the antitumor experiments in vivo. In addition, the IQuCS@Zr-PEG NSPs also had good computed tomography (CT) imaging effects, which can be used to monitor the treatment of tumors in real-time. Conclusions: The proof-of-concept strategy of upregulating tumor reoxygenation is achieved by MW triggered IQuCS@Zr-PEG NSPs, which has exhibited optimal therapeutic outcomes of combination of RT and MWTT tumor. Such unique MW-responsive reoxygenation enhancer may stimulate the research of reshaping tumor microenvironment for enhancing versatile tumor treatment.

Amplified intracellular Ca2+ for synergistic anti-tumor therapy of microwave ablation and chemotherapy.

BACKGROUND: Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS: The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS: This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

Dual-Functional Supernanoparticles with Microwave Dynamic Therapy and Microwave Thermal Therapy.

The cytotoxic reactive oxygen species (ROS) generated by photoactivated sensitizers have been well explored in tumor therapy for nearly half a century, which is known as photodynamic therapy (PDT). The poor light penetration depth severely hinders PDT as a primary or adjuvant therapy for clinical indication. Whereas microwaves (MWs) are advantageous for deep penetration depth, the MW energy is considerably lower than that required for the activation of any species to induce ROS generation. Herein we find that liquid metal (LM) supernanoparticles activated by MW irradiation can generate ROS, such as ·OH and ·O2. On this basis, we design dual-functional supernanoparticles by loading LMs and an MW heating sensitizer ionic liquid (IL) into mesoporous ZrO2 nanoparticles, which can be activated by MW as the sole energy source for dynamic and thermal therapy concomitantly. The microwave sensitizer opens the door to an entirely novel dynamic treatment for tumors.

Interlayer expansion of 2D MoS2 nanosheets for highly improved photothermal therapy of tumors in vitro and in vivo.

Interlayer-expanded MoS2 (E-MoS2) nanosheets with an interlayer spacing of 0.94 nm are demonstrated to show an high photothermal conversion efficiency of ∼62%. More importantly, such biocompatible E-MoS2 nanosheets show highly improved photothermal therapy (PTT) of tumors in vitro and in vivo under near-infrared light irradiation.

Mitochondria-targeted zirconium metal-organic frameworks for enhancing the efficacy of microwave thermal therapy against tumors.

Although microwave (MW) thermal therapy has been widely studied for the treatment of tumors due to its less invasiveness, recurrence of tumors is still observed because of the relatively low bioavailability of MW sensitizers. For enhancing the bioavailability of MW sensitizers, triphenyl phosphate (TPP)-conjugated and doxorubicin (DOX)-loaded porous zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol (PEG), ZrMOF-PEG-TPP@DOX NCs, were prepared as a MW sensitizer with mitochondrial-targeting ability. Moreover, the mitochondria are more susceptible to heat than the tumor tissues; this leads to improved tumor cell apoptosis. The results of this study indicate that ZrMOF NCs exhibit excellent heating effects due to the increased collisions of ions in the micropores of ZrMOFs under MW irradiation. In addition, ZrMOF-PEG-TPP@DOX NCs show preferential aggregation in the mitochondria, confirmed by confocal microscopy images. In vivo MW thermal therapeutic efficacy of ZrMOF-PEG-TPP@DOX NCs + MW is also better without recurrence during treatment than that of ZrMOF-PEG@DOX NCs + MW at a similar thermal therapeutic temperature; this reveals that the mitochondrial-targeting strategy can enhance the MW thermal therapeutic efficacy. This study provides a new biosafe MW sensitizer with mitochondrial-targeting ability for enhancing the efficacy of MW thermal therapy against tumors.

Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy.

Zeolitic imidazolate frameworks (ZIFs) have attracted great interest as pH-sensitive drug carrier because of high drug loading and intrinsic biodegradability. In this work, a biocompatible NIR and pH-responsive drug delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) is synthesized for in vivo cancer therapy. The biocompatibility of ZIFs is greatly improved by polydopamine (PDA) modifying and proved by cytotoxicity and in vivo acute toxicity evaluation. The degradability is also regulated in an appropriate rate. Due to mild reaction condition of ZIFs, the synthesis and drug loading is achieved in one pot with high loading (37.86%) and encapsulation rate (78.76%). Meanwhile, PDA acts as a photothermal transfer agent to trigger thermal response switch of phase change materials for NIR controlled drug release. Under the dual stimulus of NIR and acid environment, the drug release is as high as 78%, while only 21% is released without stimulus, showing a remarkable effect of control release. In vivo anti-tumor experiments demonstrate the high tumor inhibition rate of photothermal-chemotherapy group with a significant synergistic effect. The biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy.

Renal-clearable quaternary chalcogenide nanocrystal for photoacoustic/magnetic resonance imaging guided tumor photothermal therapy.

Ultrasmall Cu2ZnSnS4 (CZTS) nanocrystals with high near infrared (NIR) photothermal conversion abilities and peroxidase-mimic properties are synthesized and functionalized with bovine serum albumin (BSA) for rapid clearance multifunctional theranostic platform. Due to the presence of Cu (I) of CZTS@BSA, H2O2 could be decomposed to produce highly reactive oxygen species (ROS), catalyzed by intrinsic peroxidase like activity of CZTS. The CZTS@BSA possesses high NIR absorption and excellent photoacoustic (PA) imaging abilities. The as-prepared CZTS@BSA is also reported as an efficient T1 contrast agent for in vivo MR imaging. Therefore, in vivo distribution and rapid renal clearance of CZTS@BSA are successfully tracked by PA/MR dual-modal-imaging and further proved by ICP-MS analysis. Systemic acute toxicity evaluation indicates CZTS@BSA have good biocompatibility to normal tissues and blood. All results reveal that CZTS@BSA could act as a rapid clearance theranostic nanoplatform for dual-modal-imaging guided tumor PTT.

Microwave-Activated Mn-Doped Zirconium Metal-Organic Framework Nanocubes for Highly Effective Combination of Microwave Dynamic and Thermal Therapies Against Cancer.

Developing functional nanoagents for achieving the combination of microwave dynamic therapy (MDT) and microwave thermal therapy (MTT) is highly desirable due to the advantages of improving the therapeutic effect on tumors and minimizing the side effects. Metal-organic frameworks (MOFs), as emerging porous materials, exhibit many intriguing properties for application in biomedicine. Herein, new-style flexible Mn-doped zirconium metal-organic framework (Mn-ZrMOF) nanocubes (NCs) with the average size of about 60 nm were prepared easily by a one-pot hydrothermal method. Due to the strong inelastic collision of ions confined in a large number of micropores, the Mn-ZrMOF NCs were demonstrated to be an effective microwave-sensitive agent with a high thermal conversion efficiency up to 28.7%, which is the highest one of the recently reported microwave-sensitive agents. This is the first report of determining the microwave thermal conversion efficiency, which can be used to evaluate, compare, and predict the microwave sensitivity of different microwave-sensitive agents. More importantly, such Mn-ZrMOF NCs generate abundant reactive oxygen species (ROS) of hydroxyl radicals under microwave irradiation. As such, the Mn-ZrMOF NCs efficiently suppress the tumor cell growth in vivo and in vitro under mild microwave irradiation for the synergic effect of MTT and MDT. This work paves the way for developing nanoagents that are responsive to microwave irradiation, producing ROS and improving thermal effects to realize the noninvasive MTT and MDT treatment in clinics.

Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors.

Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO2 NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO2 nanoparticles (BB-ZrO2 NPs). The microwave energy conversion efficiency of BB-ZrO2 NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 µM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO2 NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO2 + MW group during the therapy of subcutaneous tumors even on the 42nd day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO2 + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO2 NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO2 NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and tri-stimuli-responsive chemotherapy, which may have potential applications in clinic.

In Vivo Magnetic Resonance Imaging and Microwave Thermotherapy of Cancer Using Novel Chitosan Microcapsules.

Herein, we develop a novel integrated strategy for the preparation of theranostic chitosan microcapsules by encapsulating ion liquids (ILs) and Fe3O4 nanoparticles. The as-prepared chitosan/Fe3O4@IL microcapsules exhibit not only significant heating efficacy in vitro under microwave (MW) irradiation but also obvious enhancement of T2-weighted magnetic resonance (MR) imaging, besides the excellent biocompatibility in physiological environments. The chitosan/Fe3O4@IL microcapsules show ideal temperature rise and therapeutic efficiency when applied to microwave thermal therapy in vivo. Complete tumor elimination is realizing after MW irradiation at an ultralow power density (1.8 W/cm(2)), while neither the MW group nor the chitosan microcapsule group has significant influence on the tumor development. The applicability of the chitosan/Fe3O4@IL microcapsules as an efficient contrast agent for MR imaging is proved in vivo. Moreover, the result of in vivo systematic toxicity shows that chitosan/Fe3O4@IL microcapsules have no acute fatal toxicity. Our study presents an interesting type of multifunctional platform developed by chitosan microcapsule promising for imaging-guided MW thermotherapy.

Microenvironment-Driven Bioelimination of Magnetoplasmonic Nanoassemblies and Their Multimodal Imaging-Guided Tumor Photothermal Therapy.

Biocompatibility and bioelimination are basic requirements for systematically administered nanomaterials for biomedical purposes. Gold-based plasmonic nanomaterials have shown potential applications in photothermal cancer therapy. However, their inability to biodegrade has impeded practical biomedical application. In this study, a kind of bioeliminable magnetoplasmonic nanoassembly (MPNA), assembled from an Fe3O4 nanocluster and gold nanoshell, was elaborately designed for computed tomography, photoacoustic tomography, and magnetic resonance trimodal imaging-guided tumor photothermal therapy. A single dose of photothermal therapy under near-infrared light induced a complete tumor regression in mice. Importantly, MPNAs could respond to the local microenvironment with acidic pH and enzymes where they accumulated including tumors, liver, spleen, etc., collapse into small molecules and discrete nanoparticles, and finally be cleared from the body. With the bioelimination ability from the body, a high dose of 400 mg kg(-1) MPNAs had good biocompatibility. The MPNAs for cancer theranostics pave a way toward biodegradable bio-nanomaterials for biomedical applications.

Highly stable microwave susceptible agents via encapsulation of Ti-mineral superfine powders in urea-formaldehyde resin microcapsules for tumor hyperthermia therapy.

In this study, Ti-mineral superfine powders (Ti-MSP) encapsulated in urea-formaldehyde resin microcapsules (Ti-MSP@UF-MC) were successfully prepared via a one-step microemulsion method for the first time. Because of the strong confinement effects, the Ti-MSP@UF-MC possessed perfect microwave heating effects. The temperature was 9.3 °C higher than that of the saline solution, superior to UF-MC (no significant microwave heating effect, 0 °C) and Ti-MSP (5.1 °C). The Ti-MSP@UF-MC showed low toxicity and good biocompatibility via a series of studies, including a hemolysis study and the MTT assay in vitro and in vivo. When the concentration was below 1000 µg mL(-1), the hemolysis rate was lower than 5% (hemolysis study). When the concentration was below 400 µg mL(-1), the cell activity was higher than 80% (MTT assay). Moreover, the Ti-MSP@UF-MC exhibited an ideal CT imaging effect in vivo owing to the large molecular weight of Ti-MSP. The Ti-MSP@UF-MC showed a favorable microwave therapy effect in vivo. Using mice bearing H22 tumor cells as an animal model, the tumor suppression rate could reach 100%.

Layered MoS2 Hollow Spheres for Highly-Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors.

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand-new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near-infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as-prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor-targeting delivery and cancer theranostic application.

Layered MoS2 nanoflowers for microwave thermal therapy.

Microwave (MW) hyperthermia has received great attention as an emerging green tumor thermotherapy. In this work, layered MoS2 nanoflowers were prepared through a simple bottom-up hydrothermal process. By coating MoS2 nanoflowers with bovine serum albumin (BSA-MoS2), BSA-MoS2 exhibits low biotoxicity and excellent microwave susceptive properties in vitro. Meanwhile, the heating effect improvement by the layered structure was confirmed via a computer-simulated experiment. Finally, layered BSA-MoS2 nanoflowers are designed as MW hyperthermia susceptible agents for in vivo cancer therapy with 100% tumor elimination via MW irradiation at 1.8 W, 450 MHz.