Construction of Long‐Wavelength Emissive Organic Nanosonosensitizer Targeting Mitochondria for Precise and Efficient In Vivo Sonotherapy

Abstract

As a modern biomedical therapeutic modality, sonodynamic therapy (SDT) presents unique advantages, including superior tissue penetration capability, temporal-spatial controllability, and negligible side effects. However, the bottlenecks of most organic sonosensitizers are their short emission wavelengths, strong phototoxicity, and unsatisfactory SDT effect, which undermines the precise fluorescence imaging-guided SDT in vivo. Here, a long-wavelength emissive and mitochondria-targeted organic nanosonosensitizer, named CCNU980 nanoparticles (NPs), is rationally designed, which possesses deep-tissue optical penetration (up to 6 mm), depth-activated ROS production (up to 8 cm), high photostability, and low phototoxicity. In vitro studies verify CCNU980 NPs selectively enriches in cancer cells with the ability to target the mitochondria and induce mitochondria-mediated apoptosis using abundant 1 O 2 under US irradiation. Notably, CCNU980 NPs enables precise in vivo NIR-II fluorescence imaging-guided SDT, accompanied by the suppression of the bilateral 4T1 tumor growth with minimal side effects. The current work can inspire a general strategy for the design of organic nanosonosensitizers with long-wavelength emission and new thoughts for precision medicine.

Folate Receptor‐Targeted NIR‐II Dual‐Model Nanoprobes for Multiscale Visualization of Macrophages in Rheumatoid Arthritis

“…[29] To fabricate the CF-loaded folate-targeted nano probes (FA-CF-NPs), the nano-coprecipitation method was performed (Figure 1a). [30,31] Then, a series of experiments were carried out to characterize the morphology, size, and optical properties of the obtained FA-CF-NPs. Transmission electron microscopy (TEM) imaging showed that the prepared FA-CF-NPs were spherical with an average diameter of 7.2 ± 1.3 nm (Figure 1b).…”

Recent advances in luminescent metallacycles/metallacages for biomedical imaging and cancer therapy

“…Following this work, NIR-II fluorescence imaging technology emerged and has been used in the biomedical field and other scientific research areas. 39…”

A Novel Biodegradable Nanoplatform for Tumor Microenvironments Responsive Bimodal Magnetic Resonance Imaging and Sonodynamic/Ion Interference Cascade Therapy

“…Among them, SDT, that produces ROS through sonosensitizers under US irradiation leading to cancer cell oxidative stress, necrosis, and apoptosis, has drawn much more attention due to its deep tissue penetration depth and non-invasiveness. As the key of SDT, various sonosensitizers have been explored in recent years, including organic − and inorganic sonosensitizers. The commonly used organic sonosensitizers inevitably exhibited phototoxicity and low biological stability, along with short circulation time. − Although inorganic sonosensitizers can overcome these shortcomings, such as MOFs, noble metal nanoparticles, − metallic oxide, − carbon structures derived from MOFs, black phosphorus, etc., their nonbiodegradability and potential long-term side effects are still the main obstacles to limit their further application.…”