A light-driven dual-nanotransformer with deep tumor penetration for efficient chemo-immunotherapy

Abstract

Designing a transformable nanosystem with improved tumor accumulation and penetration by tuning multiple physicochemical properties remains a challenge. Here, a near-infrared (NIR) light-driven nanosystem with size and charge dual-transformation for deep tumor penetration is developed. Methods: The core-shell nanotransformer is realized by integrating diselenide-bridged mesoporous organosilica nanoparticles as a reactive oxygen species (ROS)-responsive core with an indocyanine green (ICG)-hybrid N-isopropyl acrylamide layer as a thermosensitive shell. After loading doxorubicin (DOX), negatively charged nanomedicine prevents DOX leakage, rendering prolonged blood circulation time and high tumor accumulation. Results: Upon NIR light irradiation, mild photothermal effects facilitate the dissociation of the thermosensitive shell to achieve negative-to-positive charge reversal. Meanwhile, ICG-generated ROS cleave the diselenide bond of the organosilica core, resulting in rapid matrix degradation that produces DOX-containing smaller fragments. Such a light-driven dual-transformable nanomedicine simultaneously promotes deep tumor penetration and implements sufficient chemotherapy, along with evoking robust immunogenic cell death effects in vitro and in vivo . With the combination of a programmed cell death protein-1 (PD-1) checkpoint blockade, the nanotransformer remarkably blocks primary tumor growth and pulmonary metastasis of breast cancer with low systemic toxicity. Conclusions: This study develops a promising strategy to realize high tumor accumulation and deep penetration of light-transformable nanomedicine for efficient and safe chemo-immunotherapy.

Tuning Mesoporous Silica Nanoparticles in Novel Avenues of Cancer Therapy

“…ICG-dependent ROS generation resulted in the cleavage of diselenide bonds, resulting in rapid matrix degradation with deeper tumor penetration and inhibition of primary and metastatic tumors with low systemic toxicity. 98 2.4.4. Ultrasound-Triggered Release.…”

“…Upon NIR irradiation, photothermal stimuli mediate the dissociation of the shell for negative-to-positive charge reversal. ICG-dependent ROS generation resulted in the cleavage of diselenide bonds, resulting in rapid matrix degradation with deeper tumor penetration and inhibition of primary and metastatic tumors with low systemic toxicity …”

Biomimetic Redox-Responsive Mesoporous Organosilica Nanoparticles Enhance Cisplatin-Based Chemotherapy

“…Selenium-containing materials have attracted much attention for multiresponsive drug delivery and anticancer activities ( Sun et al, 2020 ; Birhan and Tsai, 2021 ). We recently developed a diselenide-bridged MONs that showed great potential as redox-responsive drug-delivery vehicles for controlled drug release in special tumor environments ( Shao et al, 2018a ; Chengxin Shi, 2022; Peng et al, 2022 ; Yang et al, 2022 ). Diselenide-bridged MONs achieved biodegradation in a high concentration of reductive GSH solution while scavenging; meanwhile, scavenged intracellular GSH.…”

Biomedical applications and prospects of temperature‐orchestrated photothermal therapy

“…(b) Synergy. Combining PTT with chemotherapy, photodynamic therapy (PDT), immunotherapy, and other treatments can increase efficacy and reduce side effects 29 . By tailored designing of multifunctional biomaterials, it can also achieve the therapeutic effect from tissue repair to the tumor via orchestrating temperature.…”