MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron–hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.     

纳米载体负载声敏剂的研究进展和挑战

声动力治疗是将低频超声与声敏剂相结合的非侵入性肿瘤治疗方法,由于其副作用小、治疗深度深等优点,受到科学家们的重视。有机声敏剂作为初代声敏剂已经被研究多年,但是其水溶性差、无法在肿瘤部位大量聚集等缺陷阻碍了其声动力应用。快速发展的纳米技术为许多问题的解决提供了新的思路,尤其利用纳米载体负载声敏剂,可以解决有机声敏剂水溶性差、容易被提前释放等问题,实现药物靶向作用,为声动力治疗与其他疗法结合提供平台,进一步发挥声动力治疗疗效。因此,该文总结了纳米载体负载有机声敏剂用于声动力治疗的相关研究,着重介绍纳米载体在声动力治疗中的研究进展及相关机理,指出现存问题,最终希望可以总结出用于声动力治疗的纳米载体的共性,为今后研究提供帮助。     

An Ultrasound Activated Vesicle of Janus Au‐MnO Nanoparticles for Promoted Tumor Penetration and Sono‐Chemodynamic Therapy of Orthotopic Liver Cancer

Sonodynamic therapy (SDT) has the advantages of high penetration, non‐invasiveness, and controllability, and it is suitable for deep‐seated tumors. However, there is still a lack of effective sonosensitizers with high sensitivity, safety, and penetration. Now, ultrasound (US) and glutathione (GSH) dual responsive vesicles of Janus Au‐MnO nanoparticles (JNPs) were coated with PEG and a ROS‐sensitive polymer. Upon US irradiation, the vesicles were disassembled into small Janus Au‐MnO nanoparticles (NPs) with promoted penetration ability. Subsequently, GSH‐triggered MnO degradation simultaneously released smaller Au NPs as numerous cavitation nucleation sites and Mn²⁺ for chemodynamic therapy (CDT), resulting in enhanced reactive oxygen species (ROS) generation. This also allowed dual‐modality photoacoustic imaging in the second near‐infrared (NIR) window and T₁‐MR imaging due to the released Mn²⁺, and inhibited orthotopic liver tumor growth via synergistic SDT/CDT.     

Ultrasound‐Activated Sensitizers and Applications

Modalities for photo‐triggered anticancer therapy are usually limited by their low penetrative depth. Sonotheranostics especially sonodynamic therapy (SDT), which is different from photodynamic therapy (PDT) by the use of highly penetrating acoustic waves to activate a class of sound‐responsive materials called sonosensitizers, has gained significant interest in recent years. The effect of SDT is closely related to the structural and physicochemical properties of the sonosensitizers, which has led to the development of new sound‐activated materials as sonosensitizers for various biomedical applications. This Review provides a summary and discussion of the types of novel sonosensitizers developed in the last few years and outlines their specific designs and the potential challenges. The applications of sonosensitizers with various functions such as for imaging and drug delivery as well as in combination with other treatment modalities would provide new strategies for disease therapy.     

MOF‐Derived Double‐Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging‐Guided Sonodynamic Therapy

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF‐derived double‐layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging‐guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron–hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS‐mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF‐derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.     

Porous Lanthanum-Doped Manganese Oxide Nanoparticles for Enhanced Sonodynamic Cancer Therapy

Metal oxides hold great promise as robust sonosensitizers for sonodynamic therapy (SDT). However, they usually suffer from limited production yield of reactive oxygen species (ROS) due to the fast recombination of ultrasound-triggered electrons and holes. Herein, porous lanthanum (La)-doped MnO₂ (LMO) nanoparticles are firstly developed as promising sonosensitizers in SDT. The strategic introduction of La dopants greatly promotes the separation efficiency of ultrasound-triggered electrons and holes of MnO₂, endowing them with significantly improved ROS yield. Consequently, the LMO with polyethylene glycol decoration exhibits good SDT activity toward breast cancer cells. This work highlights the doping strategy for the development of enhanced ROS production of metal oxide sonosensitizers for SDT.     

Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment

Sonodynamic therapy (SDT), as a newly emerging and promising modality for cancer treatment, has been extensively investigated but with limited therapeutic outcome because of the absence of highly efficient sonosensitizer. Copper–cysteamine (Cu–Cy), as a new sensitizer, has been reported for oxidative therapy which can be activated with light, X‐ray, or microwave. Herein, for the first time, Cu–Cy nanoparticles are reported as new sonosensitizers for SDT on breast cancer treatment. Upon exposure of Cu–Cy nanoparticles to ultrasound, a large quantity of reactive oxygen species (ROS) are generated for cancer cell destruction with a high SDT efficiency to induce cell apoptosis and necrosis as observed in vitro. In vivo animal studies show a significant inhibition of tumor growth for the xenografts of 4T1 cancer cells with the combination of 0.75 mg kg⁻¹ Cu–Cy and ultrasound. Overall, the preliminary results show that Cu–Cy nanoparticles can significantly augment the levels of ROS induced by ultrasound, demonstrating Cu–Cy is a new kind of efficient sonosensitzers for SDT applications. Such therapeutic platform by integrating a noninvasive, highly safe, deep‐penetration ultrasound modality. and quickly developed versatile nanosensitizers for tumor eradication will facilitate SDT future clinical translation.     

Sonodynamic Therapeutic Effects of Sonosensitizers with Different Intracellular Distribution Delivered by Hollow Nanocapsules Exhibiting Cytosol Specific Release

Sonodynamic therapy (SDT) is a novel promising noninvasive therapy involving utilization of low‐intensity ultrasound and sonosensitizer, which can generate reactive oxygen species (ROS) by sonication. In SDT, a high therapeutic effect is achieved by intracellular delivery and accumulation at the target sites of sonosensitizer followed by oxidative damage of produced ROS by sonication. Here, pH‐ and redox‐responsive hollow nanocapsules are prepared through the introduction of disulfide cross‐linkages to self‐assembled polymer vesicles formed from polyamidoamine dendron‐poly(l‐ lysine) for the efficient delivery of sonosensitizer. As sonosensitizer, doxorubicin (DOX), an anticancer drug accumulating into cell nucleus, is selected. Also, the conjugate of DOX and triphenylphosphonium (TPP‐DOX) is synthesized as sonosensitizer with mitochondrial targeting ability. DOX and TPP‐DOX are delivered to nucleus and mitochondria by nanocapsules. Furthermore, DOX‐ or TPP‐DOX‐loaded nanocapsules exhibit in vitro sonodynamic therapeutic effect to HeLa cells with sonication, which might be through oxidative damage to nucleus and mitochondria.