Xuan Yi

Perfluorocarbon‐Loaded Hollow Bi2Se3 Nanoparticles for Timely Supply of Oxygen under Near‐Infrared Light to Enhance the Radiotherapy of Cancer

Hollow Bi2 Se3 nanoparticles prepared by a cation exchange method are loaded with perfluorocarbon as an oxygen carrier. With these nanoparticles, a promising concept is demonstrated to enhance radiotherapy by not only using their X-ray-absorbing ability to locally concentrate radiation energy in the tumor, but also employing near-infrared light to trigger burst release of oxygen from the nanoparticles to overcome hypoxia-associated radio-resistance.

Bottom-Up Synthesis of Metal-Ion-Doped WS2 Nanoflakes for Cancer Theranostics

Recently, two-dimensional transition metal dichalcogenides (TMDCs) have received tremendous attention in many fields including biomedicine. Herein, we develop a general method to dope different types of metal ions into WS2 nanoflakes, a typical class of TMDCs, and choose Gd(3+)-doped WS2 (WS2:Gd(3+)) with polyethylene glycol (PEG) modification as a multifunctional agent for imaging-guided combination cancer treatment. While WS2 with strong near-infrared (NIR) absorbance and X-ray attenuation ability enables contrasts in photoacoustic (PA) imaging and computed tomography (CT), Gd(3+) doping offers the nanostructure a paramagnetic property for magnetic resonance (MR) imaging. As revealed by trimodal PA/CT/MR imaging, WS2:Gd(3+)-PEG nanoflakes showed efficient tumor homing after intravenous injection. In vivo cancer treatment study further uncovered that WS2:Gd(3+)-PEG could not only convert NIR light into heat for photothermal therapy (PTT) but also enhance the ionizing irradiation-induced tumor damage to boost radiation therapy (RT). Owing to the improved tumor oxygenation after the mild PTT, the combination of PTT and RT induced by WS2:Gd(3+)-PEG resulted in a remarkable synergistic effect to destroy cancer. Our work highlights the promise of utilizing inherent physical properties of TMDC-based nanostructures, whose functions could be further enriched by elementary doping, for applications in multimodal bioimaging and synergistic cancer therapy.

Catalase-Loaded TaOx Nanoshells as Bio-Nanoreactors Combining High-Z Element and Enzyme Delivery for Enhancing Radiotherapy.

A novel type of bio-nanoreactor with catalase loaded inside TaOx hollow nanoshells is fabricated via a mild one-step method. Such bio-nanoreactors could efficiently improve the tumor oxygenation by supplying oxygen via decomposition of endogenic H2 O2 in a tumor microenvironment, and thus synergistically enhance the efficacy of cancer radiotherapy by both depositing radiation energy within the tumor and overcoming hypoxia-induced radiotherapy resistance.

Radionuclide 131I labeled reduced graphene oxide for nuclear imaging guided combined radio- and photothermal therapy of cancer

Nano-graphene and its derivatives have attracted great attention in biomedicine, including their applications in cancer theranostics. In this work, we develop 131I labeled, polyethylene glycol (PEG) coated reduced nano-graphene oxide (RGO), obtaining 131I-RGO-PEG for nuclear imaging guided combined radiotherapy and photothermal therapy of cancer. Compared with free 131I, 131IRGO- PEG exhibits enhanced cellular uptake and thus improved radio-therapeutic efficacy against cancer cells. As revealed by gamma imaging, efficient tumor accumulation of 131I-RGO-PEG is observed after its intravenous injection. While RGO exhibits strong near-infrared (NIR) absorbance and could induce effective photothermal heating of tumor under NIR light irradiation, 131I is able to emit high-energy X-ray to induce cancer killing as the result of radio ionization effect. By utilizing the combined photothermal therapy and radiotherapy, both of which are delivered by a single agent 131IRGO- PEG, effective elimination of tumors is achieved in our animal tumor model experiments. Toxicology studies further indicate that 131I-RGO-PEG induces no appreciable toxicity to mice at the treatment dose. Our work demonstrates the great promise of combing nuclear medicine and photothermal therapy as a novel therapeutic strategy to realize synergistic efficacy in cancer treatment.

In Vivo Long-Term Biodistribution, Excretion, and Toxicology of PEGylated Transition-Metal Dichalcogenides MS2 (M = Mo, W, Ti) Nanosheets

With unique 2D structures and intriguing physicochemical properties, various types of transition metal dichalcogenides (TMDCs) have attracted much attention in many fields including nanomedicine. Hence, it is of great importance to carefully study the in vivo biodistribution, excretion, and toxicology profiles of different TMDCs, and hopefully to identify the most promising type of TMDCs with low toxicity and fast excretion for further biomedical applications. Herein, the in vivo behaviors of three representative TMDCs including molybdenum dichalcogenides (MoS2), tungsten dichalcogenides (WS2), and titanium dichalcogenides (TiS2) nanosheets are systematically investigated. Without showing significant in vitro cytotoxicity, all the three types of polyethylene glycol (PEG) functionalized TMDCs show dominate accumulation in reticuloendothelial systems (RES) such as liver and spleen after intravenous injection. In marked contrast to WS2‐PEG and TiS2‐PEG, which show high levels in the organs for months, MoS2‐PEG can be degraded and then excreted almost completely within one month. Further degradation experiments indicate that the distinctive in vivo excretion behaviors of TDMCs can be attributed to their different chemical properties. This work suggests that MoS2, among various TMDCs, may be particularly interesting for further biomedical applications owning to its low toxicity, capability of biodegradation, and rapid excretion.

Core–shell Au@MnO2 nanoparticles for enhanced radiotherapy via improving the tumor oxygenation

Local hypoxia in solid tumors often results in resistance to radiotherapy (RT), in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide (Au@MnO2) core–shell nanoparticles with a polyethylene glycol (PEG) coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO2 nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO2 shell may trigger the decomposition of endogenous H2O2 in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO2-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO2-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.

Radionuclide I-131 Labeled Albumin-Paclitaxel Nanoparticles for Synergistic Combined Chemo-radioisotope Therapy of Cancer

Development of biocompatible/biodegradable materials with multiple functionalities via simple methods for cancer combination therapy has attracted great attention in recent years. Herein, paclitaxel (PTX), a popular anti-tumor chemotherapeutic drug, is used to induce the self-assembly of human serum albumin (HSA) pre-labeled with radionuclide I-131, obtaining 131I-HSA-PTX nanoparticles for combined chemotherapy and radioisotope therapy (RIT) of cancer. Such 131I-HSA-PTX nanoparticles show prolonged blood circulation time, high tumor specific uptake and excellent intra-tumor penetration ability. Interestingly, as revealed by in vivo photoacoustic imaging and ex vivo immunofluorescence staining, PTX delivered into the tumor by HSA-nanoparticle transportation can remarkably enhance the tumor local oxygen level and suppress the expression of HIF-1α, leading to greatly relieved tumor hypoxia. As the results, the combined in vivo chemotherapy & RIT with 131I-HSA-PTX nanoparticles in the animal tumor model offers excellent synergistic therapeutic efficacy, likely owing to the greatly modulated tumor microenvironment associated with PTX-based chemotherapy. Therefore, in this work, a simple yet effective therapeutic agent is developed for synergistic chemo-RIT of cancer, promising for future clinic translations in cancer treatment.

Poly(Vinylpyrollidone)‐ and Selenocysteine‐Modified Bi2Se3 Nanoparticles Enhance Radiotherapy Efficacy in Tumors and Promote Radioprotection in Normal Tissues

The development of a new generation of nanoscaled radiosensitizers that can not only enhance radiosensitization of tumor tissues, but also increase radioresistance of healthy tissue is highly desirable, but remains a great challenge. Here, this paper reports a new versatile theranostics based on poly(vinylpyrollidone)- and selenocysteine-modified Bi2 Se3 nanoparicles (PVP-Bi2 Se3 @Sec NPs) for simultaneously enhancing radiotherapeutic effects and reducing the side-effects of radiation. The as-prepared nanoparticles exhibit significantly enhanced free-radical generation upon X-ray radiation, and remarkable photothermal effects under 808 nm NIR laser irradiation because of their strong X-ray attenuation ability and high NIR absorption capability. Moreover, these PVP-Bi2 Se3 @Sec NPs are biodegradable. In vivo, part of selenium can be released from NPs and enter the blood circulation system, which can enhance the immune function and reduce the side-effects of radiation in the whole body. As a consequence, improved superoxide dismutase and glutathione peroxidase activities, promoted secretion of cytokines, increased number of white blood cell, and reduced marrow DNA suppression are found after radiation treatment in vivo. Moreover, there is no significant in vitro and in vivo toxicity of PVP-Bi2 Se3 @Sec NPs during the treatment, which demonstrates that PVP-Bi2 Se3 @Sec NPs have good biocompatibility.

Drug-Loaded Mesoporous Tantalum Oxide Nanoparticles for Enhanced Synergetic Chemoradiotherapy with Reduced Systemic Toxicity.

Combining chemotherapy and radiotherapy (chemoradiotherapy) has been widely applied in many clinical practices, showing promises in enhancing therapeutic outcomes. Nontoxic nanocarriers that not only are able to deliver chemotherapeutics into tumors, but could also act as radiosensitizers to enhance radiotherapy would thus be of great interest in the development of chemoradiotherapies. To achieve this aim, herein mesoporous tantalum oxide (mTa2 O5 ) nanoparticles with polyethylene glycol (PEG) modification are fabricated. Those mTa2 O5 -PEG nanoparticles could serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin (DOX), whose release appears to be pH responsive. Meanwhile, owing to the interaction of Ta with X-ray, mTa2 O5 -PEG nanoparticles could offer an intrinsic radiosensitization effect to increase X-ray-induced DNA damages during radiotherapy. As a result, DOX-loaded mTa2 O5 -PEG (mTa2 O5 -PEG/DOX) nanoparticles can offer a strong synergistic therapeutic effect during the combined chemoradiotherapy. Furthermore, in chemoradiotherapy, such mTa2 O5 -PEG/DOX shows remarkably reduced side effects compared to free DOX, which at the same dose appears to be lethal to animals. This work thus presents a new type of mesoporous nanocarrier particularly useful for the delivery of safe and effective chemoradiotherapy.

Au@MnS@ZnS Core/Shell/Shell Nanoparticles for Magnetic Resonance Imaging and Enhanced Cancer Radiation Therapy

Although conventional radiotherapy (RT) has been widely used in the clinic to treat cancer, it often has limited therapeutic outcomes and severe toxic effects. There is still a need to develop theranostic agents with both imaging and RT-enhancing functions to improve the accuracy and efficiency of RT. Herein we synthesize Au@MnS@ZnS core/shell/shell nanoparticles with polyethylene glycol (PEG) functionalization, yielding Au@MnS@ZnS-PEG nanoparticles with great stability in different physiological solutions and no significant cytotoxicity. It is found that Au@MnS@ZnS-PEG nanoparticles can enhance the cancer cell killing efficiency induced by RT, as evidenced by multiple in vitro assays. Owing to the existence of paramagnetic Mn(2+) in the nanoparticle shell, our Au@MnS@ZnS-PEG can be used as a contrast agent for T1-weighted magnetic resonance (MR) imaging, which reveals the efficient accumulation and retention of nanoparticles in the tumors of mice after intravenous injection. Importantly, by exposing tumor-bearing mice that were injected with Au@MnS@ZnS-PEG to X-ray irradiation, the tumor growth can be significantly inhibited. This result shows clearly improved therapeutic efficacy compared to RT alone. Furthermore, no obvious side effect of Au@MnS@ZnS-PEG is observed in the injected mice. Therefore, our work presents a new type of radiosensitizing agent, which is promising for the imaging-guided enhanced RT treatment of cancer.