In vivo vagus nerve stimulation holds great promise in regulating food intake for obesity treatment. Here we present an implanted vagus nerve stimulation system that is battery-free and spontaneously responsive to stomach movement. The vagus nerve stimulation system comprises a flexible and biocompatible nanogenerator that is attached on the surface of stomach. It generates biphasic electric pulses in responsive to the peristalsis of stomach. The electric signals generated by this device can stimulate the vagal afferent fibers to reduce food intake and achieve weight control. This strategy is successfully demonstrated on rat models. Within 100 days, the average body weight is controlled at 350 g, 38% less than the control groups. This work correlates nerve stimulation with targeted organ functionality through a smart, self-responsive system, and demonstrated highly effective weight control. This work also provides a concept in therapeutic technology using artificial nerve signal generated from coordinated body activities.

A multifunctional core-satellite nanoconstruct is designed by assembling copper sulfide (CuS) nanoparticles on the surface of [ Zr]-labeled hollow mesoporous silica nanoshells filled with porphyrin molecules, for effective cancer imaging and therapy. The hybrid nanotheranostic demonstrates three significant features: (1) simple and robust construction from biocompatible building blocks, demonstrating prolonged blood retention, enhanced tumor accumulation, and minimal long-term systemic toxicity, (2) rationally selected functional moieties that interact together to enable simultaneous tetramodal (positron emission tomography/fluorescence/Cerenkov luminescence/Cerenkov radiation energy transfer) imaging for rapid and accurate delineation of tumors and multimodal image-guided therapy in vivo, and (3) synergistic interaction between CuS-mediated photothermal therapy and porphyrin-mediated photodynamic therapy which results in complete tumor elimination within a day of treatment with no visible recurrence or side effects. Overall, this proof-of-concept study illustrates an efficient, generalized approach to design high-performance core-satellite nanohybrids that can be easily tailored to combine a wide variety of imaging and therapeutic modalities for improved and personalized cancer theranostics in the future.

The mononuclear phagocyte system (MPS, e.g., liver and spleen) is often treated as a 'blackbox' by nano-researchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, we exploit this imperfection by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)related disease. Ceria nanoparticles (NPs) were selected as a representative nano-antioxidant and detailed mechanism of preventing IRI was investigated. We found that ceria NPs effectively alleviated the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines were then significantly reduced and the recruitment and infiltration of neutrophils were minimized, which suppressed subsequent inflammatory reaction involved in the liver. The protective effect of nanoantioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.

Reactive oxygen and nitrogen species (RONS) are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their use is limited by disappointing results of clinical trials. Nanoparticles are an attractive therapeutic alternative because they can change the biodistribution profile of antioxidants, and possess intrinsic ability to scavenge RONS. Herein, we review the types of RONS, how they are implicated in several diseases, and the types of nanoparticles with inherent antioxidant capability, their mechanisms of action, and their biological applications.

The interaction between radionuclides and nanomaterials could generate Cerenkov radiation (CR) for CR-induced photodynamic therapy (PDT) without requirement of external light excitation. However, the relatively weak CR interaction leaves clinicians uncertain about the benefits of this new type of PDT. Therefore, a novel strategy to amplify the therapeutic effect of CR-induced PDT is imminently required to overcome the disadvantages of traditional nanoparticulate PDT such as tissue penetration limitation, external light dependence, and low tumor accumulation of photosensitizers. Herein, magnetic nanoparticles (MNPs) with 89Zr radiolabeling and porphyrin molecules (TCPP) surface modification (i.e., 89Zr-MNP/TCPP) were synthesized for CR-induced PDT with magnetic targeting tumor delivery. As a novel strategy to break the depth and light dependence of traditional PDT, these 89Zr-MNP/TCPP exhibited high tumor accumulation under the presence of an external magnetic field, contributing to excellent tumor photodynamic therapeutic effect together with fluorescence, Cerenkov luminescence (CL), and Cerenkov resonance energy transfer (CRET) multimodal imaging to monitor the therapeutic process. The present study provides a major step forward in photodynamic therapy by developing an advanced phototherapy tool of magnetism-enhanced CR-induced PDT for effective targeting and treatment of tumors.

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS‐related diseases.

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The benefits to intracellular drug delivery from nanomedicine have been limited by biological barriers and to some extent by targeting capability.W ei nvestigated as izecontrolled, dual tumor-mitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes,P PNs). The maximum tumor accumulation (15.6 %ID g À1 ,7 2h p.i.) and ideal tumor-to-muscle ratio (16.6, 72 hp.i.) was achieved using an optimizedP PN particle sizeo fa pproximately 10 nm, as measured by using PET imaging tracing. The stable coordination of PPNs with 177 Lu enables the integration of fluorescence imaging (FL) and photodynamic therapy( PDT) with positron emission tomography (PET) imaging and internal radiotherapy( RT). Furthermore,t he efficient tumor and mitochondrial uptake of 177 Lu-PPNs greatly enhanced the efficacies of RT and/or PDT.T his work developed af acile approach for the fabrication of tumor-targeted multi-modal nanotheranostic agents,w hiche nables precision and radionuclide-based combination tumor therapy.Nanomedicine is renowned for its feasibility and controllability to create all-in-one multi-functional properties for cancer theranostics.[1] Nanoparticle-mediated combinatorial therapeutic regimens are increasingly being used by researchers to improve therapies because of their greater tumor cell killing effects at the targeted site.[2] Specifically,r adiationbased combination therapy has become aclinical standard in curative and palliative treatment regimens.[3] Recently,radionuclide therapy using particle-emitting radioisotopes (for example, 177 Lu, 90 Y, and 131 I) has presented promising results for the palliative treatment of several cancers.[4] Among those radionuclides,t he increase in 177 Lu applications has enriched its potential for research and therapeutic procedures and established it at the forefront of clinical radionuclide therapy.[5] Radioisotope 177 Lu has favorably long nuclear decay properties (t 1/2 = 6.65 d) and can be used to easily radiolabel av ariety of molecular carriers.[6] As such, 177 Lu promises to benefit nanoparticle-mediated combination therapy.Previous studies explored 177 Lu-labeled gold nanoparticles for preclinical nuclear medicine.[7] However,t he clinical translation of the reported nanosystem was impeded because of high and long-term accumulation in the reticuloendothelial system (RES) and low intratumor uptake.T hus,i tr emains ab ig challenge to integrate nanocarrier tumor-targeted delivery and multi-modal imaging using 177 Lu to obtain an anotheranostic agent with high efficiacy.Thespecificity of nanotheranostic reagents to cancer cells is critical for an efficient therapeutic effect with low side effects.[8] Am yriad of strategies have been developed to enhance cancer-targeting specificity,s uch as the conjugation of nanomaterials with target ligands. [9] In ar ecent report, mitochondria targeting emerged as apromising approach for cancer therapy.[10] However,there are several existing fundamental limitations on the design and synthesis of nanomaterials,s uch ...