Homology and Immune Checkpoint Dual-Targeted Sonocatalytic Nanoagents for Enhancing Sonodynamic Tumor Therapy

Abstract

Sonocatalytic nanoagents (SCNs), a kind of sonosensitizers, could catalyze oxygen to generate abundant reactive oxygen species (ROS) under stimulations of noninvasive and deep-penetrating ultrasound (US), which is commonly used for sonodynamic therapy (SDT) of tumors such as malignant melanoma. However, poor bioavailability of most SCNs and fast quenching of extracellular-generating ROS from SDT limit further applications of SCNs in the SDT of tumors. Herein, we synthesized a new kind of TiO 2 -based SCN functionalized with the malignant melanoma cell membrane (B16F10M) and programmed cell death-ligand 1 antibody (aPD-L1) for homology and immune checkpoint dual-targeted and enhanced sonodynamic tumor therapy. Under US irradiation, the synthesized SCN can catalytically generate a large amount of 1 O 2 .In vitro experiments validate that functionalized SCNs exhibit precise targeting effects, high tumor cell uptake, and intracellular sonocatalytic killing of the B16F10 cells by a large amount of localized ROS. Utilizing the melanoma animal model, the functionalized SCN displays visible long-term retention in the tumor area, which assists the homology and immune checkpoint synergistically dual-targeted and enhanced in vivo SDT of the tumor. We suggest that this highly bioavailable and dual-functionalized SCN may provide a promising strategy and nanoplatform for enhancing sonodynamic tumor therapies.

Surface modification of TiO2nanoparticles with organic molecules and their biological applications

“…In 2021, Wei et al synthesized newly modified TiO 2 NPs, functionalized with a malignant melanoma cell membrane (B16F10M) and a targeting aPD-L1 antibody for enhanced sonodynamic tumor therapy. 162 Under ultrasound irradiation, these modified TiO 2 NPs showed a high efficiency to generate ROS ( 1 O 2 ) along with precise targeting effects, high tumor uptake, and intracellular sonocatalytic killing of the B16F10 cells. In this study, the modification of TiO 2 NPs with the mentioned biomolecules resulted in a dramatic enhancement of biocompatibility, selectivity and therapeutic yield of the modified TiO 2 NPs.…”

Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy

“…Also, TiO 2 NPs are one of the most common sensitizers. 83 A TiO 2 -based acoustic catalytic nanosensitizer catalyzed the generation of large amounts of 1 O 2 under US irradiation 84 and oxygen-deficient black BiOCl (B-BiOCl) NPs showed more substantial 1 O 2 generation than commercial TiO 2 NPs and their derivatives. 85 Microwave (MW) as a type of electromagnetic wave has attracted significant attention in recent years.…”

Nanomaterial-based sonosensitizers: from exemplary design towards purposeful improvement

“…In order to prolong the circulation time of nanoparticles in the blood and enhance their accumulation at tumor sites, various drug delivery systems based on surface-coupled organic material strategies have been developed and are widely used in cancer therapy. 70 Among them, hyaluronic acid (HA) has good biocompatibility and biodegradability, and can bind to CD44 receptors overexpressed on the surface of tumor cells, which is commonly used in various drug delivery systems in tumor therapy. 71 Cao et al reported copper sulfide/titanium oxide heterostructured nanosheets modified with HA and PEG (HA-HNSs) for low-intensity sonodynamic and mild-photothermal synergistic therapy for early atherosclerotic plaques (Fig.…”