Tianfu Wang

Glucose‐Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving‐Like/Gas Therapy

Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H2 O2 , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2 O2 can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H2 O2 -NO cooperative anticancer effect with minimal adverse effect.

Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications

Photoacoustic imaging (PAI), a novel imaging modality based on photoacoustic effect, shows great promise in biomedical applications. By converting pulsed laser excitation into ultrasonic emission, PAI combines the advantages of optical imaging and ultrasound imaging, which benefits rich contrast, high resolution and deep tissue penetration. In this paper, we introduced recent advances of contrast agents, applications, and signal enhancement strategies for PAI. The PA contrast agents were categorized by their components, mainly including inorganic and organic PA contrast agents. The applications of PAI were summarized as follows: deep tumor imaging, therapeutic responses monitoring, metabolic imaging, pH detection, enzyme detection, reactive oxygen species (ROS) detection, metal ions detection, and so on. The enhancement strategies of PA signals were highlighted. In the end, we elaborated on the challenges and provided perspectives of PAI for deep-tissue biomedical applications.

Core–Satellite Polydopamine–Gadolinium-Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.

Black Phosphorus Nanosheets for Mild Hyperthermia-Enhanced Chemotherapy and Chemo-Photothermal Combination Therapy

Near-infrared (NIR) light triggered photothermally enhanced cellular internalization strategy shows great potential to improve antitumor effect to fight against cancer. In this work, a black phosphorus (BP) nanosheet-based nanomedicine, which is composed of BP nanosheet, human serum albumin (HSA) and paclitaxel (PTX), was developed for mild hyperthermia-enhanced intracellular drug delivery and chemo-photothermal combination therapy. BP nanosheet was successfully synthesized by a one-pot biomimetic synthesis method using HSA as exfoliating agent and capping agent. Meanwhile, PTX can be efficiently loaded by HSA via hydrophobic interactions. The PTX-loaded HSA functionalized BP (BP-HSA-PTX) exhibits great photothermal performance, excellent biodegradability/biocompatibility, and effective drug loading. Upon NIR laser illumination, mild hyperthermia (~43 °C) or photothermal effect can be achieved to improve the intracellular drug delivery efficiency and antitumor effect of BP-HSA-PTX. Our results indicate that HSA-functionalized BP has great potential for the loading, delivery, cellular uptake enhancement of chemotherapeutics and chemo-photothermal combination antitumor effect.

Facile Coordination-Precipitation Route to Insoluble Metal Roussin’s Black Salts for NIR-Responsive Release of NO for Anti-Metastasis

A facile and general coordination-precipitation method is developed to synthesize insoluble metal Roussins black salts (Me-RBSs) as a new type of NIR-responsive NORMs. The weak-field ligand coordination of metal+-RBS- brings a NIR absorption effect of Me-RBSs, and further gives rise to the NIR adsorption-dependent NIR-responsive NO release profile. Intratumoral NIR-responsive release of NO effectively inhibits the growth and metastasis of the metastatic breast cancer. Aqueous insolubility of Me-RBSs ensures lower cytotoxicity and higher thermostability compared with traditional soluble RBSs. This work establishes a new class of NIR-sensitive NO donors, and may spark new inspiration for designing intelligent gas-releasing molecules.

Photo-triggered drug delivery systems for neuron-related applications

The development of materials, chemistry and genetics has created a great number of systems for delivering antibiotics, neuropeptides or other drugs to neurons in neuroscience research, and has also provided important and powerful tools in neuron-related applications. Although these drug delivery systems can facilitate the advancement of neuroscience studies, they still have limited applications due to various drawbacks, such as difficulty in controlling delivery molecules or drugs to the target region, and trouble of releasing them in predictable manners. The combination of optics and drug delivery systems has great potentials to address these issues and deliver molecules or drugs to the nervous system with extraordinary spatiotemporal selectivity triggered by light. In this review, we will introduce the development of photo-triggered drug delivery systems in neuroscience research and their neuron-related applications including regulating neural activities, treating neural diseases and inducing nerve regenerations.

Intelligent Metal Carbonyl Metal-Organic Framework Nanocomplex for Fluorescent Traceable H2O2-Triggered CO Delivery

The recognized therapeutic benefits from carbon monoxide (CO) have caused booming attention to develop a CO therapy for various major diseases, such as cancer. However, the controlled release of CO gas and the monitoring of the CO release are vitally important to the on-demand CO administration for a safe and efficient therapy, but greatly challenging. In this work, a new CO-releasing nanocomplex was constructed by the adsorption and coordination of manganese carbonyl ([MnBr(CO)5 ], abbreviated as MnCO) with a Ti-based metal-organic framework (Ti-MOF) to realize an intratumoral H2 O2 -triggered CO release and real-time CO release monitoring by fluorescence imaging. A high CO prodrug loading capacity (0.532 g MnCO per gram Ti-MOF) is achieved due to the high surface area of Ti-MOF, and the intracellular H2 O2 -triggered CO release from the MnCO@Ti-MOF is realized to enable the nanocomplex selectively release CO in tumor cells and kill tumor cells rather than normal cells. Particularly significant is that the real-time fluorescence imaging monitoring of the CO release is realized based on an annihilation effect of the fluorescence after MnCO loading into Ti-MOF and an activation effect of the fluorescence after CO release from Ti-MOF. The quantitative relationship between the fluorescence intensity and the released CO amount is established in great favor of guiding on-demand CO administration. The results demonstrate the advantage of versatile MOFs for high efficient CO delivery and monitoring, which is critical for the improvement of the effectiveness of future therapeutic application.