Hollow MnO2-Based Nanoprobes for Enhanced Photothermal/Photodynamic /Chemodynamic Co-Therapy of Hepatocellular Carcinoma.

PURPOSE: The effect of monotherapy in cancer is frequently influenced by the tumor's unique hypoxic microenvironment, insufficient drug concentration at the treatment site, and tumour cells' increased drug tolerance. In this work, we expect to design a novel therapeutic nanoprobe with the ability to solve these problems and improve the efficacy of antitumor therapy. METHODS: We have prepared a hollow manganese dioxide nanoprobes loaded with photosensitive drug IR780 for the photothermal/photodynamic/chemodynamic co-therapy of liver cancer. RESULTS: The nanoprobe demonstrates efficient thermal transformation ability under a single laser irradiation, and under the synergistic influence of photo heat, accelerates the Fenton/ Fenton-like reaction efficiency based on Mn2+ ions to produce more ·OH under the synergistic effect of photo heat. Moreover, the oxygen released under the degradation of manganese dioxide further promotes the ability of photosensitive drugs to produce singlet oxygen (ROS). The nanoprobe has been found to efficiently destroy tumour cells in vivo and in vitro experiments when used in combination with photothermal/photodynamic/ chemodynamic modes of treatment under laser irradiation. CONCLUSION: In all, this research shows that a therapeutic strategy based on this nanoprobe could be a viable alternative for cancer treatment in the near future.

X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization.

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO2 ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn2 (CO)10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO2 . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2 , as the photolytic byproduct of Mn2 (CO)10 , has both glutathione (GSH) depletion and Fenton-like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.

Janus nanoparticles: an efficient intelligent modern nanostructure for eradicating cancer.

In the modern age, the struggle to generate appropriate bio-based materials and nano-scaled colloidal particulates for developed application domains, has already resulted in remarkable attempts in the advancement of regulated size and shape, anisotropy, and characteristics of nanostructures. The bottom-up development strategies of components are among the most important science areas throughout nanotechnology, in which the designed building blocks are often utilized to generate novel structures by random self-assembly. In biomedical applications, Janus nanoparticles (JNPs) are necessary. This is due to their effective stimulus-responsive properties, tunable structure, biocompatibility, containing two surfaces with various hydrophobic characteristics and distinct functional groups. Featuring two parts with differing hydrophobicity has been the most critical aspect of the Janus amphiphilic particles. Development of JNPs has been afforded, using imaging agents (e.g. gold (AU) for photoacoustic imaging processing (PAI), silver for surface-enhanced Raman scattering (SERS), and Fe3O4 and MnO2 to magnetic resonance imaging (MRI)). It is also to be mentioned that a number of other properties become salient - properties such as integration imaging factors into JNPs (like quantum dots, fluorescent dyes), multiple imaging methods for screening and diagnosis application can indeed be accomplished. Janus nanostructures have been promising platforms for bioengineering as therapeutic carriers, drug delivery vehicles, and biosensor equipment; they may also be employed for the transport of bioactive hydrophilic and hydrophobic materials. The main production approaches and major advancement of JNPs in the biomedical sector and cancer therapy will be described in this paper.

Acridine Orange Encapsulated Mesoporous Manganese Dioxide Nanoparticles to Enhance Radiotherapy.

Manganese dioxide (MnO2) nanoparticles are a promising type of radiosensitizer for they can catalyze H2O2 decomposition to produce O2. Combining MnO2 nanoparticles with conventional, small molecule radiosensitizers would further enhance radiotherapy (RT) efficacy due to complementary mechanisms of action. However, solid MnO2 nanoparticles are suboptimal at drug loading, limiting the related progress. Herein we report a facile method to synthesize mesoporous MnO2 (mMnO2) nanoparticles, which can efficiently encapsulate small molecule therapeutics. In particular, we found that acridine orange (AO), a small molecule radiosensitizer, can be loaded onto mMnO2 nanoparticles at very high efficiency and released to the surroundings in a controlled fashion. We show that mMnO2 nanoparticles can efficiently produce O2 inside cells. This, together with AO-induced DNA damage, significantly enhances RT outcomes, which was validated both in vitro and in vivo. Meanwhile, mMnO2 nanoparticles slowly degrade in acidic environments to release Mn2+, providing a facile way to keep track of the nanoparticles through magnetic resonance imaging (MRI). Overall, our studies suggest mMnO2 as a promising nanoplatform that can be exploited to produce composite radiosensitizers for RT.

An 808 nm Light-Sensitized Upconversion Nanoplatform for Multimodal Imaging and Efficient Cancer Therapy.

Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.

MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy.

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.

Bimetallic Oxide MnMoOX Nanorods for in Vivo Photoacoustic Imaging of GSH and Tumor-Specific Photothermal Therapy.

Accurate imaging of glutathione (GSH) in vivo is able to provide real-time visualization of physiological and pathological conditions. Herein, we successfully synthesize bimetallic oxide MnMoOX nanorods as an intelligent nanoprobe for in vivo GSH detection via photoacoustic (PA) imaging. The obtained MnMoOX nanoprobe with no near-infrared (NIR) absorption in the absence of GSH would exhibit strong GSH-responsive NIR absorbance, endowing PA imaging detection of GSH. Due to the up-regulated GSH concentration in the tumor microenvironment, our MnMoOX nanoprobe could be utilized for in vivo tumor-specific PA imaging. Moreover, MnMoOX nanorods with GSH-responsive NIR absorbance could also be employed to achieve tumor-specific photothermal therapy (PTT). Importantly, such MnMoOX nanorods show inherent biodegradability and could be rapidly cleared out from the body, minimizing their long-term body retention and potential toxicity. Our work presents a new type of GSH-responsive nanoprobe based on bimetallic oxide nanostructures, promising for tumor-specific imaging and therapy.

Oxygenic Hybrid Semiconducting Nanoparticles for Enhanced Photodynamic Therapy.

Photodynamic nanotheranostics has shown great promise for cancer therapy; however, its therapeutic efficacy is limited due to the hypoxia of tumor microenvironment and the unfavorable bioavailability of existing photodynamic agents. We herein develop hybrid core-shell semiconducting nanoparticles (SPN-Ms) that can undergo O2 evolution in hypoxic solid tumor to promote photodynamic process. Such oxygenic nanoparticles are synthesized through a one-pot surface growth reaction and have a unique multilayer structure cored and coated with semiconducting polymer nanoparticles (SPNs) and manganese dioxide (MnO2) nanosheets, respectively. The SPN core serves as both NIR fluorescence imaging and photodynamic agent, while the MnO2 nanosheets act as a sacrificing component to convert H2O2 to O2 under hypoxic and acidic tumor microenvironment. As compared with the uncoated SPN (SPN-0), the oxygenic nanoparticles (SPN-M1) generate 2.68-fold more 1O2 at hypoxic and acidic conditions under NIR laser irradiation at 808 nm. Because of such an oxygen-evolution property, SPN-M1 can effectively eradicate cancer cells both in vitro and in vivo. Our study thus not only reports an in situ synthetic method to coat organic nanoparticles but also develops a tumor-microenvironment-sensitive theranostic nanoagent to overcome hypoxia for amplified therapy.

Enhanced Cellular Ablation by Attenuating Hypoxia Status and Reprogramming Tumor-Associated Macrophages via NIR Light-Responsive Upconversion Nanocrystals.

Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period.

Continuous O2-Evolving MnFe2O4 Nanoparticle-Anchored Mesoporous Silica Nanoparticles for Efficient Photodynamic Therapy in Hypoxic Cancer.

Therapeutic effects of photodynamic therapy (PDT) are limited by cancer hypoxia because the PDT process is dependent on O2 concentration. Herein, we design biocompatible manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles (MFMSNs) to overcome hypoxia, consequently enhancing the therapeutic efficiency of PDT. By exploiting the continuous O2-evolving property of MnFe2O4 nanoparticles through the Fenton reaction, MFMSNs relieve hypoxic condition using a small amount of nanoparticles and improve therapeutic outcomes of PDT for tumors in vivo. In addition, MFMSNs exhibit T2 contrast effect in magnetic resonance imaging (MRI), allowing in vivo tracking of MFMSNs. These findings demonstrate great potential of MFMSNs for theranostic agents in cancer therapy.

Stimuli-responsive nanocomposites for magnetic targeting synergistic multimodal therapy and T1/T2-weighted dual-mode imaging.

Anticancer drug doxorubicin hydrochloride (DOX)-loaded photothermal nanocomposite MnFe2O4@mSiO2 with magnetic targeting and T1/T2-weighted dual-mode magnetic resonance imaging of MnFe2O4 core and NIR/pH-coupling sensitive mesoporous silica shell nanocarriers was designed and synthesized successfully. The anticancer drug DOX can be absorbed into mesoporous layer of MnFe2O4@mSiO2 nanocomposite, which shows obvious photothermal/chemo dual-modal synergistic therapies triggered by NIR/pH. Under 808 nm irradiation, MnFe2O4 can transform light into thermo, which can not only ablate tumor cells directly but also promote chemotherapy drugs releasing from mesoporous layer to kill tumor cells. The lower pH can also promote DOX releasing from mesoporous layer to enhance tumor inhibitory effect. It is confirmed that biocompatible DOX-MnFe2O4@mSiO2 nanocomposites can act as a potential multifunctional platform for effective magnetic targeting photothermal/chemo dual-modal synergistic therapies with enhanced anti-tumor efficacy and T1/T2-weighted dual-mode magnetic resonance imaging (MRI) applications in vivo.

Combining systemic and stereotactic MEMRI to detect the correlation between gliosis and neuronal connective pathway at the chronic stage after stroke.

BACKGROUND: The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pathological progression. The temporal patterns of astrocyte and neuronal pathway activity can be revealed by systemic and stereotactic manganese-enhanced magnetic resonance imaging (MEMRI), respectively. In the present study, we aimed to detect an association between astrocyte activity and recovery of neuronal connective pathways by combining systemic with stereotactic MEMRI. METHODS: Fifty adult rats, divided into two groups, underwent a 60-min occlusion of the middle cerebral artery. The groups were given either a systemic administration or stereotactic injection of MnCl2 at 1, 3, 7, and 14 days after stroke and underwent MRI 4 and 2 days later, respectively. Immunofluorescence (IF) of group 1 was conducted to corroborate the results. Repetitive behavioral testing was also performed with all rats at 1, 3, 7, and 14 days to obtain a functional score. RESULTS: Ring- or crescent-shaped enhancements formed in the striatal peri-infarct regions (STR) at 11 and 18 days. This was concurrent with the activity of glial fibrillary acidic protein (GFAP)-positive astrocytes, which mainly localized at the peri-infarct region and significantly increased in number at 11 and 18 days after stroke. Microglia/macrophages, detected by IF, mainly localized in the lesion core, rather than in the region of enhancement. The ipsilateral substantia nigra (SN) revealed Mn-related signal enhancement reduction and subsequent signs of the recovery process at 3 to 5 days and 9 to 16 days, respectively. Behavioral testing showed that sensorimotor functions were initially disturbed, but subsequently recovered at 7 and 14 days. CONCLUSIONS: We found a positive temporal correlation between astrogliosis and the recovery of neuronal connective pathways at the chronic stage by using the in vivo method of MEMRI. Our results highlighted the potential contribution of astrocytes to the neuronal recovery of these connective pathways.

Synthesis, Characterization and in Vitro Evaluation of Manganese Ferrite (MnFe2O4) Nanoparticles for Their Biocompatibility with Murine Breast Cancer Cells (4T1).

Manganese ferrite (MnFe2O4) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrational sample magnetometry (VSM) in order to identify the crystalline phase, functional group, morphology, particle size, shape and magnetic behavior. It was observed that the resultant spinal ferrites obtained at low temperature exhibit single phase, nanoparticle size and good magnetic behavior. The study results have revealed the existence of a potent dose dependent cytotoxic effect of MnFe2O4 nanoparticles against 4T1 cell lines at varying concentrations with IC50 values of 210, 198 and 171 µg/mL after 24 h, 48 h and 72 h of incubation, respectively. Cells exposed to higher concentrations of nanoparticles showed a progressive increase of apoptotic and necrotic activity. Below 125 µg/mL concentration the nanoparticles were biocompatible with 4T1 cells.

Biocompatibility of Mn0.4Zn0.6Fe2O4 Magnetic Nanoparticles and Their Thermotherapy on VX2-Carcinoma-Induced Liver Tumors.

Malignant tumors are the most serious threat to human health. Much research has focused on revealing the characteristics of this disease and developing methods of treatment. Because tumor cells are more sensitive to heat than normal cells, thermotherapy for the treatment of tumors has attracted much attention. In this paper, we presented functional Mn-Zn ferrite nanoparticles with the molecular composition of Mn0.4Zn0.6Fe2O4 as the magnetic response material for the thermotherapy. The suggested Mn-Zn ferrite nanoparticles were with a self-regulation temperature of 43 degrees C which was ideal for tumor thermotherapy. The biocompatibility and anti-tumor effect of this material were well investigated. It was found that the Mn0.4Zn0.6Fe2O4 nanoparticles have no hemolysis activity, no genotoxic effects and cytotoxicity. Its Median Lethal Dose (LD50) arrived at 6.026 g/kg and it did not induce any abnormal clinical signs in laboratory animals. Moreover, the suggested nanoparticles can increase the inhibitory ratio of weight and volume of tumors, cause tumor tissues necrosis and show the therapeutic effect on the xenograft live cancers in vivo. Based on these results, we could envision the valuable application of the Mn0.4Zn0.6Fe2O4 nanoparticles for the practical thermotherapy.

The anti-hepatoma effect of nanosized Mn-Zn ferrite magnetic fluid hyperthermia associated with radiation in vitro and in vivo.

Joint therapy is a promising area of study in cancer treatment. In this paper, we prepared Mn-Zn ferrite (Mn0.5Zn0.5Fe2O4) magnetofluid using PEI as a surfactant, and investigated the anticancer effect of Mn0.5Zn0.5Fe2O4 magnetic fluid hyperthermia (MFH) combined with radiotherapy on hepatocellular carcinoma. Both in vitro and in vivo results suggest that this combined treatment with MFH and radiation has a better therapeutic effect than either of them alone. The apoptotic rate and necrotic rate of the combined treatment group was 38.80 and 25.20%, respectively. In contrast, it was only 7.49 and 3.62% in the radiation-alone group, 15.23 and 7.90% in the MFH-alone group, only 3.52 and 2.16% in the blank control group, and 23.56 and 27.56% in the adriamycin group. The cell proliferation inhibition rate of the combined treatment group (88.5%) was significantly higher than that of the radiation-alone group (37.5%), MFH-alone group (60.6%) and adriamycin group (70.6%). The tumor volume inhibition and mass inhibition rate of the combined treatment group was 87.62 and 88.62%, respectively, obviously higher than the 41.04 and 34.20% of the radiation-alone group, 79.87 and 77.92% of the MFH-alone group and 71.76 and 66.87% of the adriamycin group. It is therefore concluded that this combined application of MFH and radiation can give good synergistic and complementary effects, which offers a viable approach for treatment of cancer.

Real-time infrared thermography detection of magnetic nanoparticle hyperthermia in a murine model under a non-uniform field configuration.

PURPOSE: Magnetic nanoparticle hyperthermia consists of an increase of the temperature of magnetic nanoparticles (heat centres) due to the interaction of their magnetic moments with an alternating magnetic field. In vivo experiments using this method usually use a few fibre-optic thermometers inserted in the animal body to monitor the heat deposition. As a consequence, only a few points of the 3D temperature distribution can be monitored by this invasive procedure. It is the purpose of this work to show that non-invasive infrared thermography is able to detect, in real time, magnetic nanoparticle hyperthermia as well as monitor the harmful field-induced eddy currents in a murine model with a subcutaneous tumour. This surface temperature measurement method has the potential to give information about the intratumoral temperature. MATERIALS AND METHODS: The non-invasive magnetic hyperthermia experiments were performed at 300 kHz in non-uniform field configuration conditions in healthy mice and murine tumour induced by sarcoma S180. A soft ferrite-based biocompatible magnetic colloid consisting of manganese-ferrite nanoparticles surface-coated with citric acid were used in the experiments, which were extensively characterised by several techniques (transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM)). The amplitude of the alternating magnetic fields was obtained from measurements using an AC field probe at similar experimental conditions. The temperature measurements were obtained from an infrared thermal camera and a fibre-optic thermometer. RESULTS: Three-minute magnetic hyperthermia experiments revealed surface temperature increase as high as 11 °K in healthy and (5 °K in S180 tumour) animals when injecting subcutaneously 2 mg of magnetic nanoparticles (86 µL of magnetic fluid), in contrast to around 1.5 °K (for healthy) and 2.5 °K (for cancerous) animals in experiments without the colloid due to field-induced eddy currents at the animal surface. The thermographic temperature measurements were found to agree with the fibre-optic measurements within a 5% error, and were associated with the skin emissivity angle of dependence in the experimental set-up. On the other hand, a 30-min magnetic nanoparticle hyperthermia revealed surface temperature increases as high as 12 °K close to the injection site, while above 2-3 cm no significant temperature increase was observed. Curiously, the intratumoral temperature, monitored by a fibre-optic sensor, was found to be almost the same as the thermal camera surface temperature after achieving an equilibrium temperature regime. From the observed isotherms at the animal surface, using an analytical heat conduction model, taking into account surface conductance, we estimate a magnetic heating power of 0.45 W/cm(3) and a specific loss power (SLP) of 85 W/g for a field of the order of only 10 kA/m at the injection site region. CONCLUSIONS: The results indicate that infrared thermography may be a promising tool for both early cancer detection and for hyperthermia treatment (at least for subcutaneous tumours), since the method permits access to information about the intratumoral temperature during a real-time magnetic hyperthermia as well as to estimate the in vivo nanoparticles SLP.

A nanozyme-reinforced injectable photodynamic hydrogel for combating biofilm infection.

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca2+-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO2 nanosheets and CaO2 nanoparticles for O2 self-sufficient PDT to eradicate biofilm infection. In our design, CaO2 reacts with water to produce locally concentrated H2O2, which could be catalyzed by MnO2 nanosheets (catalase-mimic nanozymes) to generate O2 and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections.

Bioinspired immuno-radio-enhancers toward synergistic nanomedicine through radiation-induced abscopal effects and immunocheckpoint blockade therapies.

Local radio-therapy combined with immunotherapy has attracted great interest in controlling local tumors. In this study, we have developed membrane-cloaked manganese dioxide nanoparticles displaying anti-PD-L1 antibodies as targeted immuno-radio-enhancers. Mediated by anti-PD-L1 antibodies (aPD-L1) expressed on cell membranes, this kind of membrane-coated nanosystem can selectively deliver cytosine-phosphate-guanine (CpG)-loaded MnO2 nanoparticles (NPs) and induce systemic anti-tumor immunities, thereby achieving favorable immuno/radio-therapeutic outcomes. Through expressing various functional proteins onto cellular membranes, the new class of membrane-camouflaged nanovehicles can be endowed with a wide variety of artificial functionalities such as enzymatic catalytic capabilities and specific targeting. This versatile nanoplatform, in general, enables the targeted delivery of theranostics, opening a new avenue for personalized nanomedicine.

Functionalized nanozyme with drug loading for enhanced tumour combination treatment of catalytic therapy and chemotherapy.

Nanozyme-based tumour catalytic therapy has attracted widespread attention in recent years, but the therapeutic efficacy is limited due to the trapping of hydroxyl radicals (˙OH) by endogenous glutathione (GSH) in the tumour microenvironment (TME). Zr/Ce-MOFs/DOX/MnO2 is constructed in this work to serve as a new kind of nanozyme for combination chemotherapy and catalytic treatment. Zr/Ce-MOFs can produce ˙OH in a mimic TME, and the MnO2 on the surface could deplete the GSH, further promoting the ˙OH generation. The pH/GSH dual stimulation accelerates the release of anticancer drug doxorubicin (DOX) in tumour tissue for enhanced tumour chemotherapy. Moreover, Mn2+ produced by the reaction of Zr/Ce-MOFs/DOX/MnO2 and GSH can be used as the contrast agent for T1-MRI. The potential antitumour effect of Zr/Ce-MOFs/DOX/MnO2 is demonstrated by in vitro and in vivo cancer treatment tests. This work thus provides a new nanozyme-based platform for enhanced combination chemotherapy and catalytic treatment for tumours.

Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma.

Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn(2+)) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T(1) shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn(2+). Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl(2) intraperitoneally three times a week. The control group was given MnCl(2) only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl(2) enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn(2+).