Zhimin Chang

Janus Gold Nanoplatform for Synergetic Chemoradiotherapy and Computed Tomography Imaging of Hepatocellular Carcinoma

There is a pressing need to develop nanoplatforms that integrate multimodal therapeutics to improve treatment responses and prolong the survival of patients with unresectable hepatocellular carcinoma (HCC). Mesoporous silica-coated gold nanomaterials have emerged as a novel multifunctional platform combining tunable surface plasmon resonance and mesoporous properties that exhibit multimodality properties in cancer theranostics. However, their reduced radiation-absorption efficiency and limited surface area hinder their further radiochemotherapeutic applications. To address these issues, we designed Janus-structured gold-mesoporous silica nanoparticles using a modified sol-gel method. This multifunctional theranostic nanoplatform was subsequently modified via the conjugation of folic acid for enhanced HCC targeting and internalization. The loaded anticancer agent doxorubicin can be released from the mesopores in a pH-responsive manner, facilitating selective and safe chemotherapy. Additionally, the combination of chemotherapy and radiotherapy induced synergistic anticancer effects in vitro and exhibited remarkable inhibition of tumor growth in vivo along with significantly reduced systematic toxicity. Additionally, the Janus NPs acted as targeted computed tomography (CT)-imaging agents for HCC diagnosis. Given their better performance in chemoradiotherapy and CT imaging as compared with that of their core-shell counterparts, this new nanoplatform designed with dual functionalities provides a promising strategy for unresectable HCC theranostics.

Core-Shell Magnetic Gold Nanoparticles for Magnetic Field-Enhanced Radio-Photothermal Therapy in Cervical Cancer

The combination of radiotherapy (RT) and photothermal therapy (PTT) has been considered an attractive strategy in cervical cancer treatment. However, it remains a challenge to simultaneously enhance the radio-sensitivity of tumor tissue, develop tumor tissue-focused radiation therapies and combine dual therapeutic modalities. In this study, core-shell type magnetic gold (Fe3O4@Au) nanoparticles are exploited to achieve the synergistic efficacy of radio-photothermal therapy in cervical cancer. Fe3O4@Au nanoparticles (NPs) with uniform morphology exhibited superior surface plasmon resonance properties, excellent superparamagnetic properties, good biocompatibility and high photothermal conversion efficiency. For the in vitro tests, a low concentration of Fe3O4@Au NPs after a short period of near-infrared irradiation lead to the time-dependent death of cervical cancer cells. Further, the combination of RT and PTT induced synergistic anti-cancer effects in vitro. More importantly, an external magnetic field could significantly enhance the synergistic efficacy of Fe3O4@Au NPs by improving their internalization. Hence, the reported Fe3O4@Au NPs have the potential to be good nanoagents with excellent magnetic targeting ability for cervical cancer radio-photothermal treatment.

Berberine‐loaded Janus Nanocarriers for Magnetic Field‐Enhanced Therapy Against Hepatocellular Carcinoma

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3O4‐mSiO2 NPs) consisting of a Fe3O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH‐sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment‐responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug‐loading amounts, superior endocytic ability, and low cytotoxicity. Berberine‐loaded Fe3O4‐mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH‐responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber‐loaded Fe3O4‐mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.

Bioinspired Diselenide‐Bridged Mesoporous Silica Nanoparticles for Dual‐Responsive Protein Delivery

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide-bond-containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual-responsiveness is reported. These diselenide-bridged MSNs can encapsulate cytotoxic RNase A into the 8-10 nm internal pores via electrostatic interaction and release the payload via a matrix-degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer-cell-derived membrane fragments, these bioinspired RNase A-loaded MSNs exhibit homologous targeting and immune-invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti-cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell-membrane-coated, dual-responsive degradable MSNs represent a promising platform for the delivery of bio-macromolecules such as protein and nucleic acid therapeutics.

Janus Silver/Silica Nanoplatforms for Light-Activated Liver Cancer Chemo/Photothermal Therapy

Stimuli-triggered nanoplatforms have become attractive candidates for combined strategies for advanced liver cancer treatment. In this study, we designed a light-responsive nanoplatform with folic acid-targeting properties to surmount the poor aqueous stability and photostability of indocyanine green (ICG). In this Janus nanostructure, ICG was released on-demand from mesoporous silica compartments in response to near-infrared (NIR) irradiation, exhibiting predominant properties to convert light to heat in the cytoplasm to kill liver cancer cells. Importantly, the silver ions released from the silver compartment that were triggered by light could induce efficient chemotherapy to supplement photothermal therapy. Under NIR irradiation, ICG-loaded Janus nanoplatforms exhibited synergistic therapeutic capabilities both in vitro and in vivo compared with free ICG and ICG-loaded mesoporous silica nanoparticles themselves. Hence, our Janus nanoplatform could integrate ICG-based photothermal therapy and silver ion-based chemotherapy in a cascade manner, which might provide an efficient and safe strategy for combined liver cancer therapy.

Shape Engineering Boosts Magnetic Mesoporous Silica Nanoparticle-Based Isolation and Detection of Circulating Tumor Cells

Magnetic mesoporous silica nanoparticles (M-MSNs) are attractive candidates for the immunomagnetic isolation and detection of circulating tumor cells (CTCs). Understanding of the interactions between the effects of the shape of M-MSNs and CTCs is crucial to maximize the binding capacity and capture efficiency as well as to facilitate the sensitivity and efficiency of detection. In this work, fluorescent M-MSNs were rationally designed with sphere and rod morphologies while retaining their robust fluorescence and uniform surface functionality. After conjugation with the antibody of epithelial cell adhesion molecule (EpCAM), both of the differently shaped M-MSNs-EpCAM obtained achieved efficient enrichment of CTCs and fluorescent-based detection. Importantly, rodlike M-MSNs exhibited faster immunomagnetic isolation as well as better performance in the isolation and detection of CTCs in spiked cells and real clinical blood samples than those of their spherelike counterparts. Our results showed that shape engineering contributes positively toward immunomagnetic isolation, which might open new avenues to the rational design of magnetic-fluorescent nanoprobes for the sensitive and efficient isolation and detection of CTCs.

Magnetic Janus nanorods for efficient capture, separation and elimination of bacteria

Magnetic Janus mesoporous silica nanoparticles (MSNs) with CTAB-loading and amino-functionalization were prepared through a one-pot synthesis strategy. Janus MSNs exhibit outstanding bacterial capture and separation performance, enabling the highly efficient elimination of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, illustrating their application potential in biomedicine.

Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles

Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.

Theoretical Study on the Photoinduced Electron Transfer Mechanisms of Different Peroxynitrite Probes

The development of probes for rapid and selective detection of peroxynitrite in vivo is of great importance in biological science. We investigate different photoinduced electron transfer (PIET) processes of two generations of peroxynitrite probes. Each has fluorescein and phenol moieties; one is conjugated by an ether linkage while the other is conjugated via an amine linkage. Using theoretical calculations, we demonstrated that the PIET in the probe with an ether linkage occurs from the benzoic acid to the xanthene moiety. In contrast, the PIET in the probe with an amine linkage occurs from the phenol moiety to the fluorescein. This suggests that better sensitivity can be accomplished in probes with an amine linkage than with an ether linkage. Following this model, we designed two novel peroxynitrite probes and simulated their detection capabilities in the near-infrared region.

A highly selective fluorescent probe for cyanide ion and its detection mechanism from theoretical calculations

A new cyanide probe has been prepared by one-step synthesis and evaluated by UV-vis and fluorescent method. This probe is combined by a fluorene part and a hemicyanine group through a conjugated linker, which is found to show rapid response, high selectivity and sensitivity for cyanide anions with significant dual colorimetric and fluorescent signal changes in aqueous solution. An intramolecular charge transfer (ICT) effect plays a key role in the CN- sensing properties, and the details of this mechanism are further supported by DFT and TD-DFT calculations. The theoretical study shows that the introduction of CN- twists the original plane structure and blocks the ICT process in the whole molecule, which brings about the absorption blue-shift and the fluorescence quenching.