Shao-Kai Sun

Fabrication of multifunctional Gd2O3/Au hybrid nanoprobe via a one-step approach for near-infrared fluorescence and magnetic resonance multimodal imaging in vivo.

Facile fabrication of multimodal imaging probes is highly desired for bioimaging application due to their integrated advantages of several imaging modalities. Here, we report a simple and one-step mild strategy to fabricate a multifunctional Gd2O3/Au hybrid nanoprobe. Bovine serum albumin (BSA) was used as the template in the biomineralization synthesis. The fabricated BSA-Gd2O3/Au nanoprobe showed excellent chemical stability, intense near-infrared (NIR) fluorescence, and good magnetic resonance imaging (MRI) ability. The multimodal imaging potential of the prepared multifunctional nanoprobe was demonstrated by successful NIR fluorescent and magnetic resonance blood pool imaging. Further modification of BSA-Gd2O3/Au with arginine-glycine-aspartic acid peptide c(RGDyK) (RGD) enabled the nanoprobe for targeted tumor imaging in vivo.

Hyaluronic acid-mediated one-pot facile synthesis of a sensitive and biocompatible Gd2O3 nanoprobe for MR imaging in vivo

MR contrast agents play a crucial role in the early diagnosis of various diseases, and many nanoprobes with versatile properties have been developed. However, in order to seek high sensitivity, the biocompatibility and systemic toxicity assessment of the nanoprobes have attracted much less attention. To meet clinical requirements, it is highly desirable to develop a highly sensitive and biocompatible nanoprobe using a facile procedure. Herein, we report a sensitive and biocompatible Gd2O3 nanoprobe using hyaluronic acid (HA) via a one-pot facile synthesis. HA not only endows the nanoprobe with excellent biocompatibility, but also gives a synergistic effect for improving the sensitivity of the nanoprobe in the aspects of increasing rotational correlation time, water exchange rate and the ratio of surface Gd3+ to the inner ones. What’s more, the nanoprobe has specific ability for adrenal gland MR imaging. These results suggest that the HA–Gd2O3 nanoprobe has a potentially promising application in MR imaging in vivo.

Antigen‐Directed Fabrication of a Multifunctional Nanovaccine with Ultrahigh Antigen Loading Efficiency for Tumor Photothermal‐Immunotherapy

Current antigen-encapsulated multifunctional nanovaccines for oncotherapy suffer from limited antigen loading efficiency, low yield, tedious manufacture, and systemic toxicity. Here, an antigen-directed strategy for the fabrication of multifunctional nanovaccine with ultrahigh antigen loading efficiency in a facile way for tumor photothermal-immunotherapy is shown. As a proof of concept, a model antigen ovalbumin (OVA) is used as a natural carrier to load a representative theranostic agent indocyanine green (ICG). Mixing OVA and ICG in aqueous solution gives the simplest multifunctional nanovaccine so far. The nanovaccine owns antigen loading efficiency of 80.8%, high yield of >90%, intense near-infrared absorption and fluorescence, excellent reproducibility, good aqueous solubility and stability, and favorable biocompatibility. These merits not only guarantee sensitive labeling/tracking and efficient stimulation of dendritic cells, but also reliable imaging-guided photothermal-immunotherapy of tumors and tumor prevention. The proposed strategy provides a facile and robust method for large-scale and reproducible fabrication of multifunctional nanovaccines with ultrahigh antigen loading efficiency for tumor therapy.

Biomineralization of Versatile CuS/Gd2 O3 Hybrid Nanoparticles for MR Imaging and Antitumor Photothermal Chemotherapy.

The versatile application of nanoparticles in integrating imaging and therapy has aroused extensive research interest in precision medicine. Of the various nanoparticles that have been studied, CuS has shown great potential in the construction of multifunctional agents, owing to its excellent photothermal heating properties. Herein, we report a facile one-pot biomineralization approach for the preparation of versatile bovine-serum-albumin-conjugated CuS/Gd2 O3 hybrid nanoparticles (BSA-CuS/Gd2 O3 HNPs), which simultaneously possessed strong longitudinal relaxivity, an outstanding photothermal effect, high drug-loading capacity, and pH/temperature-responsive drug release. The versatile nanoparticles were used for magnetic resonance imaging (MRI) and antitumor photothermal chemotherapy, both in vitro and in vivo. In vivo MRI showed that the BSA-CuS/Gd2 O3 HNPs had a long circulation time and effective passive tumor-uptake ability. More importantly, combined in vitro and in vivo therapy demonstrated that drug-loaded BSA-CuS/Gd2 O3 HNPs offered outstanding synergistic therapeutic efficacy for tumor inhibition.

Engineering Persistent Luminescence Nanoparticles for Biological Applications: From Biosensing/Bioimaging to Theranostics

Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the nature of interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in guiding the design of PLNPs nanoprobes and promoting further development of PLNPs in the fields of biological science and medicine. We conclude this Account by outlining the future directions to further promote the practical application of PLNPs. The novel protocols for the synthesis of small-size, monodisperse, and water-soluble PLNPs with high NIR PL intensity and superlong afterglow are the vibrant directions for the biomedical applications of PLNPs. In-depth theories and evidence on luminescence mechanism of PLNPs are highly desired for further improvement of their luminescence performance. Furthermore, other irradiations without tissue penetrating depth limit, such as X-ray, are encouraged for use in energy storage and re-excitation of PLNPs, enabling imaging in deep tissue in vivo and integrating other X-ray sensitized theranostic techniques such as computed tomography imaging and radiotherapy. Last but not least, PLNPs-based nanoprobes and the brand new hybrids of PLNPs with other nanomaterials show a bright prospect for accurate diagnosis and efficient treatment of diseases besides tumors.