Elaborately designed biocompatible nanoplatforms simultaneously having diverse therapeutic and imaging functions are highly desired for biomedical applications. Herein, a BiSe nanoagent with a special morphology as a nanoscale spherical sponge (NSS) has been fabricated and investigated in vitro and in vivo. The highly porous NSS exhibits strong, steady, and broad-band absorbance in the near-infrared range as well as high efficiency and stability of photothermal conversion, resulting in high antitumor efficacy for photothermal therapy (PTT). Together with a high X-ray attenuation coefficient (218% that of the clinically used iopromide), the NSS shows excellent performance on triple-modal high-contrast imaging, including X-ray-computed tomography, multispectral optoacoustic tomography, and infrared thermal imaging. Furthermore, the high surface area and porous structure impart the NSS a competent drug loading capability as high as 600% of that on BiSe nanoplates, showing a bimodal pH/photothermal sensitive drug release and pronounced synergetic effects of thermo-chemotherapy with a tumor inhibition ratio even higher than that of PTT alone (∼94.4% vs ∼66.0%). Meanwhile, the NSS is highly biocompatible with rather low in vitro/in vivo toxicity and high stability, at variance with easily oxidized BiSe nanoagents reported previously. Such biocompatible single-component theranostic nanoagents produced by a facile synthesis and highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials for clinical antitumor applications. This highly porous nanostructure with a large fraction of void space may allow versatile use of the NSS, for example, in catalysis, gas sensing, and energy storage, in addition to accommodating drugs and other biomolecules.

Development of stimuli-responsive theranostics is of great importance for precise cancer diagnosis and treatment. Herein, bovine serum albumin (BSA) modified bismuth nanoraspberries (Bi-BSA NRs) are developed as cancer theranostic agents for multimodal imaging and chemo-photothermal combination therapy. The Bi-BSA NRs are synthesized in aqueous phase via a facile reduction method using Bi 2 O 3 nanospheres as the sacrificial template. The morphology, biocompatibility, photothermal effect, drug loading/releasing abilities, chemotherapy effect, synergistic chemo-photothermal therapy efficacy, and multimodal imaging capacities of Bi-BSA NRs have been investigated. The results show that the NRs possess multiple unique features including (i) raspberry-like morphology with high specific surface area (∼52.24 m 2 •g −1 ) and large cavity (total pore volume ∼0.30 cm 3 •g −1 ), promising high drug loading capacity (∼69 wt %); (ii) dual-stimuli responsive drug release, triggered by acidic pH and NIR laser irradiation; (iii) infrared thermal (IRT), photoacoustic (PA) and X-ray computed tomography (CT) trimodality imaging with the CT contrast enhanced efficiency as high as ∼66.7 HU•mL•mg −1 ; (iv) 100% tumor elimination through the combination chemo-photothermal therapy. Our work highlights the great potentials of Bi-BSA NRs as a versatile theranostics for multimodal imaging and combination therapy.

Biocompatible single-component nanoplatforms simultaneously integrating multiple therapeutic functions with multiple imaging modes are desirable for anticancer treatments. Herein, elaborately-designed highly porous PEGylated bismuth sulfide nano-urchins (Bi2S3-PEG NUs) have been successfully synthesized by using Bi2O3 nanospheres as the sacrificial template via the hydrothermal process. It is demonstrated that the Bi2S3-PEG NUs possess high compatibility, stability, X-ray attenuation ability, near-infrared (NIR) absorbance and photothermal conversion capability, without noticeable toxicity. Based on both in vitro and in vivo results, the product shows excellent performance in highly effective photothermal therapy (PTT) guided by triple-modal imaging, including X-ray computed tomography (CT), and photoacoustic (PA) and infrared thermal (IRT) imaging, without noticeable toxicity in vivo. Importantly, the NUs are highly porous with a high specific surface area and copious mesopores, providing high loading capacity to accommodate drugs (or guest biomolecules) for further applications in chemotherapy and other additional functions. Doxorubicin is loaded as an example, showing a rather high loading capacity (∼37.9%) together with a bimodal on-demand pH/photothermal-sensitive drug release property. Such fascinating multifunctional nanoagents may have considerable applications in antitumor diagnosis and therapy in the clinic.

Near-infrared light-mediated theranostic agents with superior tissue penetration and minimal invasion have captivated researchers in cancer research in the past decade. Herein, a probe sonication-assisted liquid exfoliation approach for scalable and continual synthesis of colloidal rhenium disulfide nanosheets, which is further explored as theranostic agents for cancer diagnosis and therapy, is reported. Due to high-Z element of Re (Z = 75) and significant photoacoustic effect, the obtained PVP-capped ReS nanosheets are evaluated as bimodality contrast agents for computed tomography and photoacoustic imaging. In addition, utilizing the strong near-infrared absorption and ultrahigh photothermal conversion efficiency (79.2%), ReS nanosheets could also serve as therapeutic agents for photothermal ablation of tumors with a tumor elimination rate up to 100%. Importantly, ReS nanosheets show no obvious toxicity based on the cytotoxicity assay, serum biochemistry, and histological analysis. This work highlights the potentials of ReS nanosheets as a single-component theranostic nanoplatform for bioimaging and antitumor therapy.

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