Smart Nanosensitizers for Activatable Sono‐Photodynamic Immunotherapy of Tumors by Redox‐Controlled Disassembly

Abstract

Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumortargeted and redox-activatable nanosensitizers (1-NPs) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r 1 = 18.7 � 0.3 mM À 1 s À 1 ), but "off" dual fluorescence (FL) emission (at 547 and 672 nm), "off" sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd, Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emission, (2) sonophotodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imagingguided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.

A Fast and Reversible Responsive Bionic Transmembrane Nanochannel for Dynamic Single-Cell Quantification of Glutathione

“…51 The development of a single-cell nanodevice for in situ quantification of the GSH homeostasis during cancer treatment is important for understanding the pathophysiological processes. Here, phenylphosphonic acid zinc (Zn-PPa)-based photodynamic therapy (PDT) 45,46 was introduced to verify the potential of the nanochannel to address this issue. The optimized incubation time of 12 h and Zn-PPa concentration of 10 μM were used to ensure adequate cellular uptake of Zn-PPa (Figure S29).…”

“…To explore the feasibility, we quantified the subcellular GSH levels in three different types of cancer cells, i.e., HeLa, SK-BR-3 and MDA-MB-435 cells, respectively. Rapid GSH alterations induced by photodynamic therapy (PDT) , were also unveiled, showing the distinct decrease of GSH levels both in cytosol and vesicles. Furthermore, the nanochannel was also used for the time-lapse monitoring and detection of cytosolic GSH during ferroptosis. , …”

Recent Advances in Activatable Probes for Molecular Imaging by Stimuli‐Controlled Disassembly

“…Using the same disassembly approach controlled by GSH and HSA, they further developed smart paramagnetic prodrug and photosensitizer nanoassemblies for bimodal FLI/MRI guided synergistic therapy of orthotopic gliomas in living mice. [ 66, 67 ]…”

Improvement of the effectiveness of sonodynamic therapy: by optimizing components and combination with other treatments

“…14). 167 Unfortunately, the hypoxic environment of the tumor greatly inhibits the efficiency of SPDT. To that end, Duan et al constructed a nanoplatform based on Fenton-like reactions (Pd@MOF-525@HA) to alleviate tumor hypoxia through oxygen-generating strategies for enhancing oxygen-dependent anti-tumor therapy.…”