Shunhao Wang

Metal–Organic‐Framework‐Derived Mesoporous Carbon Nanospheres Containing Porphyrin‐Like Metal Centers for Conformal Phototherapy

Mesoporous carbon nanospheres containing porphyrin-like metal centers (denoted as PMCS) are successfully synthesized by the pyrolysis of an imidazolate framework using a mesoporous-silica protection strategy. The PMCS allow infrared and photoacoustic imaging and synergetic photothermal therapy/photodynamic therapy derived from the porphyrin-like moieties, offering the possibility of real-time monitoring of therapeutic processes and image-guided precise conformal phototherapy. PMCS thus represent a novel multifunctional theranostic platform for improved treatment efficiencies.

Advances in biodegradable nanomaterials for photothermal therapy of cancer

Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser.

Mesoporous carbon nanomaterials induced pulmonary surfactant inhibition, cytotoxicity, inflammation and lung fibrosis

Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials (MCNs) is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics, energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774A.1 macrophages and lung epithelial A549 cells. Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs. Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis. Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial.

Bio-transformation of Graphene Oxide in Lung Fluids Significantly Enhances Its Photothermal Efficacy

Rationale: Graphene oxide (GO) has shown great promises in biomedical applications, such as drug delivery and thermotherapeutics, owing to its extraordinary physicochemical properties. Nonetheless, current biomedical applications of GO materials are premised on the basis of predesigned functions, and little consideration has been given to the influence of bio-transformation in the physiological environment on the physicochemical properties and predesigned functionalities of these materials. Hence, it is crucial to uncover the possible influence on GOs physicochemical properties and predesigned functionalities for better applications. Methods: Bio-transformed GOs were characterized by X-ray diffraction (XRD) spectra, Raman spectra, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared transmission (FT-IR) spectra. The morphologies of various GO materials were assessed via transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) images. The photothermal (PTT) performance of different GO materials in vitro and in vivo were measured using 808 nm laser at a power density of 2 W/cm2. The PTT efficacy was determined using transplanted 4T1 cells-derived breast tumors in mice. Results: Bio-transformation of GO in the lung (a main target organ for GO to localize in vivo) can induce dramatic changes to its physicochemical properties and morphology, and consequently, its performances in biomedical applications. Specifically, GO underwent significant reduction in two simulated lung fluids, Gambles solution and artificial lysosomal fluid (ALF), as evidenced by the increase of C/O ratio (the ratio of C content to O content) relative to pristine GO. Bio-transformation also altered GOs morphology, characterized by sheet folding and wrinkle formation. Intriguingly, bio-transformation elevated the PTT performance of GO in vitro, and this elevation further facilitated PTT-based tumor-killing efficacy in tumor cells in vitro and in a mouse model with transplanted tumors. Bio-transformation also compromised the interaction between drug with GO, leading to reduced drug adsorption, as tested using doxorubicin (DOX). Conclusions: Transformation in Gambles solution and ALF resulted in varied degrees of improved performances of GO, due to the differential effects on GOs physicochemical properties. Our findings unveiled an overlooked impact of GO bio-transformation, and unearthed a favorable trait of GO materials in thermotherapeutics and drug delivery in the lung microenvironment.

Reduction of graphene oxide alters its cyto-compatibility towards primary and immortalized macrophages

Graphene oxide (GO) and its derivatives (e.g., reduced graphene oxide, RGO) have shown great promise in biomedicine. Although many studies have been conducted to understand the relative cyto-compatibility between GO and RGO materials, the results are inconclusive and controversial. In this study, we compared the biocompatibility aspects (e.g. cytotoxicity, pro-inflammatory effects and impairment of cellular morphology) between parental and reduced GOs towards macrophages using primary bone marrow-derived macrophages (BMDMs) and J774A.1 cell line. Two RGOs (RGO1 and RGO2) with differential reduction levels relative to the parental GO were prepared. Intriguingly, besides loss of oxygen-containing functional groups, significant morphological alteration of GO occurred, from the sheet-like structure to a polygonal curled shape for RGO, without significant aggregation in biological medium. Cytotoxicity assessment unveiled that the RGOs were more toxic than pristine GO to both types of cells. It was surprising to find for the first time (to our knowledge) that GO and RGOs elicited different effects on the morphological changes of BMDMs, as reflected by elongated protrusions from GO treatment and shortened protrusions from the RGOs. Furthermore, RGOs induced greater pro-inflammatory responses than GO, especially in BMDMs. Compromised cyto-compatibility of RGOs was attributable (at least partially) to their greater oxidative stress in macrophages. Mechanistically, these differences in bio-reactivities between GO and RGO should be boiled down to (at least in part) the synergistic effects from the variation of oxygen-containing functional groups and the distinct morphology in between. This study unearthed the crucial contribution of reduction-mediated detrimental cellular effects between GO and RGO towards macrophages.

From the lung to the knee joint: Toxicity evaluation of carbon black nanoparticles on macrophages and chondrocytes

Carbon black (CB), a core elemental carbon component of airborne particles, has been used as a model material to study environmental safety and health impacts of airborne particles. Although potential adverse effects of CB have been reported, limited knowledge is available regarding CB-induced metabolic disorders and secondary effects distant from primary target organs, such as the effects on joints. The knee cavity is a relatively closed space along the peripheral circulation route with a slow rate of interchange of nutrition with blood. While epidemiologic studies have indicated that airborne particle exposure may affect the occurrence and severity of inflammatory knee diseases, no research has been performed to understand the potential hazardous direct/indirect interactions between particles and knee cells. Herein, we have scrutinized the toxicity of four commercial nano-sized CB samples in the lung and a distant site: knee joint. Our results indicated that CB triggered pulmonary and systemic inflammation upon inhalation exposure, and, more strikingly, CB also elicited injuries of the knee joint, as demonstrated by thickened synovial membrane, suggesting disordered cellular metabolism within the knee joint. Our data recognized the CB toxicity profiles to macrophages as characterized by pro-inflammatory reactions, and also defined an activated metabolic state of chondrocytes, as evidenced by metalloproteinase (MMP) induction. Of note, remarkable variations were also found for these changes induced by these four CB samples, due to their distinct physicochemical properties. Collectively, our results uncovered a significant toxicity of CB inhalation exposure to the knee joint, as reflected by metabolic activation of chondrocytes, and, more importantly, these findings unearthed CB-induced metabolic disorders and secondary effects owing to systemic pro-inflammatory conditions upon CB exposure, in addition to the likelihood of direct toxicity to knee cells.