Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics

The clinical application of cisplatin (CisPt) is limited by its dose-dependent toxicity. To overcome this, we developed reduction-responsive nanoparticles (NP(3S)s) for the targeted delivery of a platinum(IV) (Pt(IV)) prodrug to improve efficacy and reduce the toxicity. NP(3S)s could release Pt(II) and hydrogen sulfide (H 2 S) upon encountering intracellular glutathione, leading to potent anticancer effects. Notably, NP(3S)s induced DNA damage and activated the STING pathway, which is a known promoter for T cell activation. Comparative RNA profiling revealed that NP(3S)s outperformed CisPt in enhancing T cell immunity, antitumor immunity, and oxidative stress pathways. In vivo experiments showed that NP(3S)s accumulated in tumors, promoting CD8 + T cell infiltration and boosting antitumor immunity. Furthermore, NP(3S)s exhibited robust in vivo anticancer efficacy while minimizing the CisPt-induced liver toxicity. Overall, the results indicate NP(3S)s hold great promise for clinical translation due to their low toxicity profile and potent anticancer activity.

Section: Discussionmentioning

confidence: 99%

A Trisulfide Bond Containing Biodegradable Polymer Delivering Pt(IV) Prodrugs to Deplete Glutathione and Donate H₂S to Boost Chemotherapy and Antitumor Immunity

Li,

Cai,

Zhang

et al. 2024

“…ROS are chemically active oxygen-containing molecules, including singlet oxygen ( 1 O 2 ), H 2 O 2 , O 2 •– , hydroxyl radical (•OH), and hypochlorite (OCl – ), − which play a crucial role in regulating physiology and pathology processes and are often overexpressed in various inflammatory tissues. − Therefore, the design of ROS-responsive ratiometric FL probes is of great value for the diagnosis and therapy of diseases. Song and co-workers designed a smart ratiometric NIR-II FL probe (DCNP@786s) consisting of IR786s-coated lanthanide-based down-conversion NPs (DCNPs) for the sensing of ROS in vivo and quantitatively tracking adoptive natural killer (NK) cell viability (Figure a) .…”

Section: Ratiometric Optical Imagingmentioning

confidence: 99%

Activatable Probes for Ratiometric Imaging of Endogenous BiomarkersIn Vivo

Fu,

Yang,

Wang

et al. 2024

Self Cite

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of realtime detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

“…Owing to the physicochemical properties of nanomaterials, nanomedicines could overcome the drawbacks of traditional drugs, including improved dispersity, enhanced blood circulation, less blood clearance, and improved tumor targeting. Nanomedicines possess outstanding performances in enhancing treatment efficacy and reducing side effects. − Currently, nanomedicines can be administered in various ways, such as intravenous injection ( i.v. ), oral administration ( p.o.…”

Section: Fundamental Question Of Nanomedicinesmentioning

confidence: 99%

Nanomedomics

Liang,

Cao,

Tang

et al. 2024

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.