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Glioma is the most frequent primary brain tumour of the central nervous system. Its high aggressiveness and deep‐seated brain lesion make it a great challenge to develop a non‐invasive, precise and effective treatment approach. Here, we report a multifunctional theranostic agent that can integrate imaging and therapy into a single nano‐platform for imaging‐guided sonodynamic therapy (SDT). The SDT agents were fabricated by encapsulation of sinoporphyrin sodium (DVDMS) chelating with manganese ions into nanoliposomes (DVDMS‐Mn‐LPs). DVDMS‐Mn‐LPs are physiologically stable and biologically compatible, and they can produce singlet oxygen upon ultrasound irradiation to kill cancer cells. Both cell and animal studies demonstrated that SDT with DVDMS‐Mn‐LPs can significantly improve the antitumour growth efficiency even in the presence of skull. In addition, DVDMS‐Mn‐LPs are good for MR and fluorescence imaging. Thus, DVDMS‐Mn‐LPs reported here may provide a promising strategy for imaging‐guided modality for glioma treatment.

Lanthanide-based NIR-IIb nanoprobes are ideal for in vivo imaging. However, existing NIR-IIb nanoprobes often suffer from low tumor-targeting specificity, limiting their widespread use. Here the application of bioorthogonal nanoprobes with high tumor-targeting specificity for in vivo NIR-IIb luminescence imaging and magnetic resonance imaging (MRI) is reported. These dual-modality nanoprobes can enhance NIR-IIb emission by 20-fold and MRI signal by twofold, compared with non-bioorthogonal nanoprobes in murine subcutaneous tumors. Moreover, these bioorthogonal probes enable orthotopic brain tumor imaging. Implementation of bio-orthogonal chemistry significantly reduces the nanoprobe dose and hence cytotoxicity, providing a paradigm for real-time in vivo visualization of tumors.

Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single-layer (S-MoS2), few-layer (F-MoS2), and multi-layer (M-MoS2) nanosheets by the albumin-assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M-MoS2 to S-MoS2 can both significantly enhance the near-infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S-MoS2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S-MoS2 to both U87 subcutaneous and orthotopic tumor-bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S-MoS2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.

Oxygen nanocarrier (A/D-ONC) with a polymeric core entrapping hemoglobin and a cationic lipid shell absorbing a DOX-intercalating DNA duplex is developed. After endocytosis oxygenated A/D-ONC donates O2 to cancer cells that acts therapeutically by: (1) increasing intracellular ATP content that promotes DOX release, thereby converting ATP to the trigger of detrimental chemotherapy; (2) by synchronously increasing the ROS amount to amplify the lethality to cancer cells.

Controlling synthesis of near-infrared emitting quantum rods (QRs) for in vivo imaging is a major challenge in the fabrication of multifunctional nanoprobes. Here, a reliable synthetic approach for CdTe x Se1–x /ZnS alloy nanocrystals to achieve highly bright (quantum yields up to 80%) with controllable rod-shape and near-infrared (650–870 nm) emission is developed. Aspect ratio and emission of QRs are correlated with composition, which can be easily tuned by changing Te and Se mole ratio. It illustrates that the content of Se plays an important role in maintaining the rod-shape, while Te has a significant impact on emitting of the nanorods. Besides exhibiting great stability over a broad range of pH (4–10) and ion strength (up to 2 mol L-1 NaCl solution), these hydrophilic QRs display good photo stability and storage stability. In particular, the specially absorbing of paramagnetic gadolinium ions on the QRs lead to a versatile method to engineer multimodal imaging nanoprobes, which are applied for in vivo lymph node dual-modal imaging (fluorescence and magnetic resonance imaging). These results suggest a promising strategy for engineering multifunctional imaging nanoprobes with the stable near-infrared QRs.

Brain tumor is one of the most lethal cancers owing to the existence of blood-brain barrier and blood-brain tumor barrier as well as the lack of highly effective brain tumor treatment paradigms. Herein, cyclo(Arg-Gly-Asp-D-Phe-Lys(mpa)) decorated biocompatible and photostable conjugated polymer nanoparticles with strong absorption in the second near-infrared (NIR-II) window are developed for precise photoacoustic imaging and spatiotemporal photothermal therapy of brain tumor through scalp and skull. Evidenced by the higher efficiency to penetrate scalp and skull for 1064 nm laser as compared to common 808 nm laser, NIR-II brain-tumor photothermal therapy is highly effective. In addition, via a real-time photoacoustic imaging system, the nanoparticles assist clear pinpointing of glioma at a depth of almost 3 mm through scalp and skull with an ultrahigh signal-to-background ratio of 90. After spatiotemporal photothermal treatment, the tumor progression is effectively inhibited and the survival spans of mice are significantly extended. This study demonstrates that NIR-II conjugated polymer nanoparticles are promising for precise imaging and treatment of brain tumors.

The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging‐guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2− xSe particles on the surface and doxorubicin inside the hollow interior, is synthesized. The developed multifunctional theranostic nanosystems exhibit tumor‐triggered programmed destruction due to the reducing microenvironment‐responsive cleavage of disulfide bonds that are incorporated into the framework of HMONs and linked between HMONs and Cu2− xSe, resulting in tumor‐specific biodegradation and on‐demand drug‐releasing behavior. Such tumor microenvironment‐responsive biodegradable and biocompatible theranostic nanosystems in combination with FUS provide a promising delivery nanoplatform with high performance for orthotopic brain tumor imaging and therapy.