Carbon Nitride Hollow Theranostic Nanoregulators Executing Laser-Activatable Water Splitting for Enhanced Ultrasound/Fluorescence Imaging and Cooperative Phototherapy

Abstract

The limited efficacy of “smart” nanotheranostic agents in eradicating tumors calls for the development of highly desirable nanoagents with diagnostics and therapeutics. Herein, to surmount these challenges, we constructed an intelligent nanoregulator by coating a mesoporous carbon nitride (C3N4) layer on a core–shell nitrogen-doped graphene quantum dot (N-GQD)@hollow mesoporous silica nanosphere (HMSN) and decorated it with a P-PEG-RGD polymer, to achieve active-targeting delivery (designated as R-NCNP). Upon irradiation, the resultant R-NCNP nanoregulators exhibit significant catalytic breakdown of water molecules, causing a sustainable elevation of oxygen level owing to the C3N4 shell, which facilitates tumor oxygenation and relieves tumor hypoxia. The generated oxygen bubbles serve as an echogenic source, triggering tissue impedance mismatch, thereby enhancing the generation of an echogenicity signal, making them laser-activatable ultrasound imaging agents. In addition, the encapsulated photosensitizers and C3N4-layered photosensitizer are simultaneously activated to maximize the yield of ROS, actualizing a triple-photosensitizer hybrid nanosystem exploited for enhanced PDT. Intriguingly, the N-GQDs endow the R-NCNP nanoregulator with a photothermal effect for hyperthemia, making it exhibit considerable photothermal outcomes and infrared thermal imaging (IRT). Importantly, further analysis reveals that the polymer-modified R-NCNPs actively target specific tumor tissues and display a triple-modal US/IRT/FL imaging-assisted cooperative PTT/PDT for real-time monitoring of tumor ablation and therapeutic evaluation. The rational synergy of triple-model PDT and efficient PTT in the designed nanoregulator confers excellent anticancer effects, as evidenced by in vitro and in vivo assays, which might explore more possibilities in personalized cancer treatment.

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging‐Guided Synergistic Therapy

“…The laser power density of 1.0 W cm −2 was employed in this work, which is considered as safe and acceptable in the previously reported work for in vivo photothermal evaluation. [ 21,49,50 ]…”

“…The laser power density of 1.0 W cm −2 was employed in this work, which is considered as safe and acceptable in the previously reported work for in vivo photothermal evaluation. [21,49,50] Excitingly, the RPA assemblies underwent secondary selfassembly under NIR laser irradiation. The PLGA segments of monodispersed RPA were fused together into larger hierarchal superstructure with two or more rings on the surface of PLGA matrix (Figure 6h and Figure S11, Supporting Information).…”

Temperature Feedback‐Controlled Photothermal/Photodynamic/Chemodynamic Combination Cancer Therapy Based on NaGdF4:Er,Yb@NaGdF4:Nd@Cu‐BIF Nanoassemblies

“…The injection concentration was determined based on in vitro experiments, which is consistent with previous studies. [ 28 ] As shown in Figure 5b, the CSNPs@Cu‐BIF nanoassemblies were injected intravenously into nude mice for 12 h (the maximum accumulation time of the sample in the tumor), and thermal imaging was recorded under 808 nm laser irradiation. In G4, the temperature of the tumor increases to 57.5 °C in 7 min, which is sufficient to effectively eliminate solid tumors.…”

Synergy of Tumor Microenvironment Remodeling and Autophagy Inhibition to Sensitize Radiation for Bladder Cancer Treatment

“…Recently, we found that manganese dioxide nanoparticles (MnO 2 ) were a safe and effective nano-agent that could improve a hypoxic and acidic tumor microenvironment 13 - 15 . MnO 2 efficiently reacted to the excessive H 2 O 2 and H + in the TME and generated oxygen to modulate hypoxic, acidic, and high-ROS tumor microenvironments 16 - 20 . Therefore, we wanted to explore the possibility of MnO 2 as an autophagy inhibition.…”