Adhesive Ergothioneine Hyaluronate Gel Protects against Radiation Gastroenteritis by Alleviating Apoptosis, Inflammation, and Gut Microbiota Dysbiosis.

Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.

Biocompatible Tantalum Nanoparticles as Radiosensitizers for Enhancing Therapy Efficacy in Primary Tumor and Metastatic Sentinel Lymph Nodes.

Metastasis of breast carcinoma is commonly realized through lymphatic circulation, which seriously threatens the lives of breast cancer patients. Therefore, efficient therapy for both primary tumor and metastatic sentinel lymph nodes (SLNs) is highly desired to inhibit cancer growth and metastasis. During breast cancer treatment, radiotherapy (RT) is a common clinical method. However, the efficacy of RT is decreased by the radioresistance to a hypoxic microenvironment and inevitable side effects for healthy issues at high radiation doses. Considering the above-mentioned, we provide high biocompatible poly(vinylpyrrolidone) coated Ta nanoparticles (Ta@PVP NPs) for photothermal therapy (PTT) assisted RT for primary tumor and metastatic SLNs. On the one hand, for primary tumor treatment, Ta@PVP NPs with a high X-ray mass attenuation coefficient (4.30 cm2/kg at 100 keV) can deposit high radiation doses within tumors. On the other hand, for metastatic SLNs treatment, the effective delivery of Ta@PVP NPs from the primary tumor into SLNs is monitored by computed tomography and photoacoustic imaging, which greatly benefit the prognosis and treatment for metastatic SLNs. Moreover, Ta@PVP NPs-mediated PTT could enhance the RT effect, and immunogenic cell death caused by RT/PTT could induce an immune response to improve the therapeutic effect of metastatic SLNs. This study not only explores the potential of Ta@PVP NPs as effective radiosensitizers and photothermal agents for combined RT and PTT but also offers an efficient strategy to cure both primary tumor and metastatic SLNs in breast carcinoma.

Photothermal Killing of A549 Cells and Autophagy Induction by Bismuth Selenide Particles.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been completed on the relevant mechanism underlying the photothermal killing effect of Bi2Se3. Herein, the photothermal effects of Bi2Se3 particles on A549 cells were explored with emphasis put on autophagy. First, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of microtubule-associated protein 1 light chain 3-II (LC3-II) to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon near infrared (NIR) irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 particles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways, including p38 and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), were activated, coupled with the attenuated PI3K/Akt signaling. Our study finds that autophagy and the activation of stress-related signaling pathways are involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal materials.

X-ray-facilitated redox cycling of nanozyme possessing peroxidase-mimicking activity for reactive oxygen species-enhanced cancer therapy.

Nanomaterials with shifting or mixed redox states is one of the most common studied nanozyme with peroxidase-like activity for chemodynamic therapy (CDT), which can decompose hydrogen peroxide (H2O2) of tumor microenvironment into highly toxic reactive oxygen species (ROS) by a nano-catalytic way. However, most of them exhibit an insufficient catalytic efficiency due to their dependence on catalytic condition. Herein, a potential methodology is proposed to enhance their enzymatic activity by accelerating the redox cycling of these nanomaterials with shifting or mixed redox states in the presence of X-ray. In this study, the nanocomposite consisting of SnS2 nanoplates and Fe3O4 quantum dots with shifting or mixed redox states (Fe2+/Fe3+) is used to explore the strategy. Under external X-ray irradiation, SnS2 cofactor as electron donor can be triggered to transfer electrons to Fe3O4, which promotes the regeneration of Fe2+ sites on the surface of the Fe3O4. Consequently, the regenerated Fe2+ sites react with the overexpressed H2O2 to persistently generate ROS for enhanced tumor therapy. The designed nanocomposite displays the synergistic effects of radiotherapy and CDT. The strategy provides a new avenue for the development of artificial nanozymes with shifting or mixed redox states in precise cancer treatments based on X-ray-enhanced enzymatic efficacy.

A Heterojunction Structured WO2.9-WSe2 Nanoradiosensitizer Increases Local Tumor Ablation and Checkpoint Blockade Immunotherapy upon Low Radiation Dose.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO2.9-WSe2-PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H2O2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.

BiO2-x Nanosheets as Radiosensitizers with Catalase-Like Activity for Hypoxia Alleviation and Enhancement of the Radiotherapy of Tumors.

Tumor hypoxia is known to be one of the vital factors that aggravate tumor resistance to radiation therapy (RT) in which oxygen plays a critical role in tumor destruction. Herein, we synthesize a simple nanoradiosensitizer based on ultrathin BiO2-x nanosheets (NSs) modified with Tween 20 (T-BiO2-x NSs) to overcome the hypoxia-induced radioresistance as well as increase the efficacy of RT. On the one hand, bismuth as a high-Z element can effectively enhance the sensitivity of RT by depositing a higher radiation dose in tumors. The semiconductor property also endows its photocatalytic ability to produce extra reactive oxygen species (ROS) by reaction with the surrounding water. On the other hand, the defect-abundant BiO2-x NSs are also found to decompose the highly expressed hydrogen peroxide (H2O2) at the tumor site into oxygen (O2) for combating hypoxia. Both in vitro and in vivo experiments indicate that the as-prepared T-BiO2-x NSs could effectively inhibit tumor growth with X-ray irradiation. Our work thus provides a simple nanoradiosensitizer with multifunctionalities for increasing the RT efficacy while alleviating tumor hypoxia at the same time.

Enhanced Generation of Non-Oxygen Dependent Free Radicals by Schottky-type Heterostructures of Au-Bi2S3 Nanoparticles via X-ray-Induced Catalytic Reaction for Radiosensitization.

Despite the development of nanomaterials with high-Z elements for radiosensitizers, most of them suffer from their oxygen-dependent behavior in hypoxic tumor, nonideal selectivity to tumor, or inevasible damages to normal tissue, greatly limiting their further applications. Herein, we develop a Schottky-type heterostructure of Au-Bi2S3 with promising ability of reactive free radicals generation under X-ray irradiation for selectively enhancing radiotherapeutic efficacy by catalyzing intracellular H2O2 in tumor. On the one hand, like many other nanomaterials with rich high-Z elements, Au-Bi2S3 can deposit higher radiation dose within tumors in the form of high energy electrons. On the other hand, Au-Bi2S3 can remarkably improve the utilization of a large number of X-ray-induced low energy electrons during radiotherapy for nonoxygen dependent free radicals generation even in hypoxic condition. This feature of Schottky-type heterostructures Au-Bi2S3 attributes to the generated Schottky barrier between metal Au and semiconductor Bi2S3, which can trap the X-ray-generated electrons and transfer them to Au, resulting in efficient separation of the electron-hole pairs. Then, because of the matched potential between the conduction band of Bi2S3 and overexpressed H2O2 within tumor, the Au-Bi2S3 HNSCs can decompose the intracellular H2O2 into highly toxic •OH for selective radiosensitization in tumor. As a consequence, this kind of nanoparticle provides an idea to develop rational designed Schottky-type heterostructures as efficient radiosensitizers for enhanced radiotherapy of cancer.

Enhanced radiosensitization of ternary Cu3BiSe3 nanoparticles by photo-induced hyperthermia in the second near-infrared biological window.

The development of a new multifunctional nanomedicine capable of enhancing radiosensitization by photo-induced hyperthermia for the inhibition of cancer growth and metastasis is highly required for efficient treatment of cancer cells. Compared to the first near-infrared (NIR) window, the second NIR window light could provide a maximum penetration depth as well as minimizing autofluorescence due to its low scattering and energy absorption. Here, we report a new versatile theranostic agent based on ternary Cu3BiSe3 nanoparticles (NPs) modified by poly(vinylpyrollidone) (PVP-Cu3BiSe3). Benefiting from their preferable X-ray attenuation ability and strong NIR absorbance in the second NIR biological window, PVP-Cu3BiSe3 NPs can not only deposit more radiation doses to destroy the cancer cells, but also conduct the optical energy into hyperthermia for thermal eradication of tumor tissues and the improvement of the tumor oxygenation to overcome the hypoxia-associated radio-resistance of tumors. According to both in vitro and in vivo results, exposure to an X-ray plus 1064 nm laser completely kills cancer cells and even inhibits tumor metastasis, displaying no warning signs of a relapse. On the other hand, PVP-Cu3BiSe3 NPs can be used as a multi-model imaging agent for X-ray computer tomography (CT) and photoacoustic tomography (PAT) imaging. These demonstrate the potential of PVP-Cu3BiSe3 NPs in multimodal imaging-guided synergetic radiophotothermal therapy of deep-seated tumors and effective inhibition of their metastasis.

Mass production of poly(ethylene glycol) monooleate-modified core-shell structured upconversion nanoparticles for bio-imaging and photodynamic therapy.

Developing robust and high-efficient synthesis approaches has significant importance for the expanded applications of upconversion nanoparticles (UCNPs). Here, we report a high-throughput synthesis strategy to fabricate water-dispersible core-shell structured UCNPs. Firstly, we successfully obtain more than 10 grams core UCNPs with high quality from one-pot reaction using liquid rare-earth precursors. Afterwards, different core-shell structured UCNPs are fabricated by successive layer-by-layer strategy to get enhanced fluorescence property. Finally, the hydrophobic UCNPs are modified with poly(ethylene glycol) monooleate (PEG-OA) though a novel physical grinding method. On the basis of mass-production, we use the as-prepared PEG-UCNPs to construct an 808-nm stimuli photodynamic therapy agent, and apply them in cancer therapy and bio-imaging.

Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone-modified 2H-phase nano-MoS2.

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.

Tumor Microenvironment-Responsive Cu2(OH)PO4 Nanocrystals for Selective and Controllable Radiosentization via the X-ray-Triggered Fenton-like Reaction.

Traditional radiotherapy can induce injury to the normal tissue around the tumor, so the development of novel radiosensitizer with high selectivity and controllability that can lead to more effective and reliable radiotherapy is highly desirable. Herein, a new smart radiosensitizer based on Cu2(OH)PO4 nanocrystals that can simultaneously respond to endogenous stimulus (H2O2) and exogenous stimulus (X-ray) is reported. First, Cu2(OH)PO4 nanocrystals can generate CuI sites under X-ray irradiation through X-ray-induced photoelectron transfer process. Then, X-ray-triggered CuI sites serve as a catalyst for efficiently decomposing overexpressed H2O2 in the tumor microenvironment into highly toxic hydroxyl radical through the Fenton-like reaction, finally inducing apoptosis and necrosis of cancer cells. Meanwhile, this nonspontaneous Fenton-like reaction is greatly limited within normal tissues because of its oxygen-rich condition and insufficient H2O2 relative to tumor tissues. Thus, this strategy can ensure that the process of radiosentization can only be executed within hypoxic tumors but not in normal cells, resulting in the minimum damages to surrounding healthy tissues. As a result, the X-ray-triggered Fenton-like reaction via introducing nontoxic Cu2(OH)PO4 nanocrystals under the dual stimuli provides a more controllable and reliable activation approach to simultaneously enhance the radiotherapeutic efficacy and reduce side effects.

Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement.

Radioresistance resulted from the intrinsic features of tumors often gives rise to unsatisfied therapeutic outcome. In particular, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H2O2) and hypoxia has been believed as a tremendous obstacle for radiotherapy. Therefore, developing an effective radiosensitizer in response to both X-ray and the TME is highly imperative but remains a challenge so far. Here, we for the first time explore bismuth heteropolytungstate (BiP5W30) nanoclusters as radiosensitizers for the TME-manipulated enhancement of radiotherapy. On the one hand, BiP5W30 nanoclusters can increase radiation dose deposition within tumors by high-Z elements like Bi and W. On the other hand, in virtue of the unique electron structure and multi-electron property, they have the capability of depleting glutathione (GSH) via redox reaction and catalyzing the decomposition of H2O2 to HO to enhance ROS generation upon X-ray radiation. Moreover, reduced graphene oxide (rGO) coupled with BiP5W30 can further improve radiocatalytic activity through promoting electron-hole separation. Simultaneously, due to the considerable near-infrared absorption of rGO, photothermal therapy can overcome the tumor hypoxia microenvironment and thus synergize with radiotherapy. In addition to providing a promising radiosensitizer, this finding is expected to extend the application of polyoxometalates used in the biomedical field.

Graphdiyne Nanoparticles with High Free Radical Scavenging Activity for Radiation Protection.

Numerous carbon networks materials comprised of benzene moieties, such as graphene and fullerene, have held great fascination for radioprotection because of their acknowledged good biocompatibility and strong free radical scavenging activity derived from their delocalized π-conjugated structure. Recently, graphdiyne, a new emerging carbon network material consisting of a unique chemical structure of benzene and acetylenic moieties, has gradually attracted attention in many research fields. Encouraged by its unique structure with strong conjugated π-system and highly reactive diacetylenic linkages, graphdiyne might have free radical activity and can thus be used as a radioprotector, which has not been investigated so far. Herein, for the first time, we synthesized bovine serum albumin (BSA)-modified graphdiyne nanoparticles (graphdiyne-BSA NPs) to evaluate their free radical scavenging ability and investigate their application for radioprotection both in cell and animal models. In vitro studies indicated that the graphdiyne-BSA NPs could effectively eliminate the free-radicals, decrease radiation-induced DNA damage in cells, and improve the viability of cells under ionizing radiation. In vivo experiments showed that the graphdiyne-BSA NPs could protect the bone marrow DNA of mice from radiation-induced damage and make the superoxide dismutase (SOD) and malondialdehyde (MDA) (two kinds of vital indicators of radiation-induced injury) recover back to normal levels. Furthermore, the good biocompatibility and negligible systemically toxicity responses of the graphdiyne-BSA NPs to mice were verified. All these results manifest the good biosafety and radioprotection activity of graphdiyne-BSA NPs to normal tissues. Therefore, our studies not only provide a new radiation protection platform based on graphdiyne for protecting normal tissues from radiation-caused injury but also provide a promising direction for the application of graphdiyne in the biomedicine field.

Functionalized MoS2 Nanovehicle with Near-Infrared Laser-Mediated Nitric Oxide Release and Photothermal Activities for Advanced Bacteria-Infected Wound Therapy.

The rising dangers of bacterial infections have created an urgent need for the development of a new generation of antibacterial nanoagents and therapeutics. A new near-infrared 808 nm laser-mediated nitric oxide (NO)-releasing nanovehicle (MoS2 -BNN6) is reported through the simple assembly of α-cyclodextrin-modified MoS2 nanosheets with a heat-sensitive NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6) for the rapid and effective treatment of three typical Gram-negative and Gram-positive bacteria (ampicillin-resistant Escherichia coli, heat-resistant Escherichia faecalis, and pathogen Staphylococcus aureus). This MoS2 -BNN6 nanovehicle has good biocompatibility and can be captured by bacteria to increase opportunities of NO diffusion to the bacterial surface. Once stimulated by 808 nm laser irradiation, the MoS2 -BNN6 nanovehicle not only exhibits photothermal therapy (PTT) efficacy but also can precisely control NO release, generating oxidative/nitrosative stress. The temperature-enhanced catalytic function of MoS2 induced by 808 nm laser irradiation simultaneously accelerates the oxidation of glutathione. This acceleration disrupts the balance of antioxidants, ultimately resulting in significant DNA damage to the bacteria. Within 10 min, the MoS2 -BNN6 with enhanced PTT/NO synergetic antibacterial function achieves >97.2% inactivation of bacteria. The safe synergetic therapy strategy can also effectively repair wounds through the formation of collagen fibers and elimination of inflammation during tissue reconstruction.

Bi2 S3 -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal Therapy of LoVo Cells In Vitro and In Vivo.

Although various types of photothermal agents are developed for photothermal cancer therapy, relatively few photothermal agents exhibit high tumor inhibition rate under relatively mild conditions. Herein, a multifunctional Bi2 S3 -Tween 20 nanoplatform loaded with PI3K inhibitor LY294002 is designed as a novel photothermal agent for inhibitor and photothermal synergistic therapy of tumors under mild photothermal therapy conditions. The LY294002 of PI3K inhibitor, after being loaded by Bi2 S3 -Tween 20 nanodots, exhibits greatly increased drug utilization and reduced side effects on normal tissues. In vivo, Bi2 S3 -Tween 20@LY294002 upon near-infrared 808 nm laser irradiation shows potent antitumor activity under relatively mild conditions (power density: 0.6 W cm-2 ). Moreover, the mechanism studies also demonstrate that Bi2 S3 -Tween 20@LY294002 potently kills LoVo cancer cells under low-power near-infrared light irradiation, by downregulating the expression of heat shock protein 70 (HSP70) so as to increase the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated mitochondrial apoptosis pathway. The results demonstrate that the newly synthesized multifunctional nanoplatform paves a new avenue for accurate therapy of photothermal-resistant cancer.

X-Ray-Controlled Generation of Peroxynitrite Based on Nanosized LiLuF4 :Ce3+ Scintillators and their Applications for Radiosensitization.

Peroxynitrite (ONOO- ), the reaction product derived from nitric oxide (NO) and superoxide (O2 -• ), is a potent oxidizing and nitrating agent that modulates complex biological processes and promotes cell death. Therefore, it can be expected that the overproduction of ONOO- in tumors can be an efficient approach in cancer therapy. Herein, a multifunctional X-ray-controlled ONOO- generation platform based on scintillating nanoparticles (SCNPs) and UV-responsive NO donors Roussin's black salt is reported, and consequently the mechanism of their application in enhanced therapeutic efficacy of radiotherapy is illustrated. Attributed to the radioluminescence and high X-ray-absorbing property of SCNPs, the nanocomposite can produce NO and O2 -• simultaneously when excited by X-ray irradiation. Such simultaneous release of NO and O2 -• ensures the efficient X-ray-controlled generation of ONOO- in tumors. Meanwhile, the application of X-rays as the excitation source can achieve better penetration depth and induce radiotherapy in this nanotherapeutic platform. It is found that the X-ray-controlled ONOO- -generation platform can efficiently improve the radiotherapy efficiency via directly damaging DNA, downregulating the expression of the DNA-repair enzyme, and overcoming the hypoxia-associated resistance in radiotherapy. Therefore, this SCNP-based platform may provide a new combinatorial strategy of ONOO- and radiotherapy to improve cancer treatment.

A Size-Reducible Nanodrug with an Aggregation-Enhanced Photodynamic Effect for Deep Chemo-Photodynamic Therapy.

Fluorescent dyes with multi-functionality are of great interest for photo-based cancer theranostics. However, their low singlet oxygen quantum yield impedes their potential applications for photodynamic therapy (PDT). Now, a molecular self-assembly strategy is presented for a nanodrug with a remarkably enhanced photodynamic effect based on a dye-chemodrug conjugate. The self-assembled nanodrug possesses an increased intersystem crossing rate owing to the aggregation of dye, leading to a distinct singlet oxygen quantum yield (Φ(1 O2 )). Subsequently, upon red light irradiation, the generated singlet oxygen reduces the size of the nanodrug from 90 to 10 nm, which facilitates deep tumor penetration of the nanodrug and release of chemodrug. The nanodrug achieved in situ tumor imaging and potent tumor inhibition by deep chemo-PDT. Our work verifies a facile and effective self-assembly strategy to construct nanodrugs with enhanced performance for cancer theranostics.

Small size fullerenol nanoparticles suppress lung metastasis of breast cancer cell by disrupting actin dynamics.

BACKGROUND: Tumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis. RESULTS: In this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young's modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility. CONCLUSIONS: With intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.

Biodegradable MoOx nanoparticles with efficient near-infrared photothermal and photodynamic synergetic cancer therapy at the second biological window.

Near-infrared (NIR) laser induced phototherapy has been considered as a noninvasive option for cancer therapy. Herein, we report plasmonic PEGylated molybdenum oxide nanoparticles (PEG-MoOx NPs) that were synthesized by using a facile hydrothermal method. The PEG-MoOx NPs exhibit broad absorption at the NIR biological window and remarkable photothermal conversion ability in the first (808 nm) and the second (1064 nm) windows. Moreover, the biocompatible PEG-MoOx NPs exhibit effective cellular uptake and could be eliminated gradually from the liver and spleen in mice. Studies on the therapeutic effects of these NPs under 808 and 1064 nm exposures with mild hyperthermia are conducted. According to the result, exposure to 1064 nm irradiation can not only effectively convert light into heat but also sensitize the formation of reactive oxygen species (ROS), which exert dramatic cancer cell death and suppression in vivo due to the synergic effect of photothermal therapy (PTT) and photodynamic therapy (PDT). In marked contrast, 808 nm irradiation can only execute limited PTT to cancer cells, showing a relatively low inhibition rate in vitro and in vivo. This biodegradable MoOx nanoplatform with synergetic PTT and PDT functionalities upon 1064 nm irradiation provided emerging opportunities for the phototherapy of cancer in nanomedicine.

Intelligent MoS2 Nanotheranostic for Targeted and Enzyme-/pH-/NIR-Responsive Drug Delivery To Overcome Cancer Chemotherapy Resistance Guided by PET Imaging.

Chemotherapy resistance remains a major hurdle for cancer therapy in clinic because of the poor cellular uptake and insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS2 nanotheranostic (MoS2-PEI-HA) ingeniously decorated with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with the chemotherapy drug doxorubicin (DOX). HA can not only target CD44-overexpressing MCF-7-ADR but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment, thus accelerating DOX release. Furthermore, MoS2 with strong near-infrared (NIR) photothermal conversion ability can also promote the release of DOX in the acidic tumor environment at a mild 808 nm laser irradiation, achieving a superior antitumor activity based on the programmed response to HAase and NIR laser actuator. Most importantly, HA targeting combined with mild NIR laser stimuli, rather than using hyperthermia, can potently downregulate the expression of drug-resistance-related P-glycoprotein (P-gp), resulting in greatly enhanced intracellular drug accumulation, thus achieving drug resistance reversal. After labeled with 64Cu by a simple chelation strategy, MoS2 was employed for real-time positron emission tomography (PET) imaging of MCF-7-ADR tumor in vivo. This multifunctional nanoplatform paves a new avenue for PET imaging-guided spatial-temporal-controlled accurate therapy of drug-resistant cancer.