Reactive oxygen species (ROS)-responsive nanoprobe for bioimaging and targeting therapy of osteoarthritis

Chong Shen,Ming Gao,Li Zheng,Wei Xiong,Haimin Chen,Zhimin Li,Jinmin Zhao,Zainen Qin,Yanting Zhan,Qiumei Lan

doi:10.1186/s12951-021-01136-4

Abstract

Stimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly “turn on” in response to excessive ROS and “turn off” in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics.Graphical

Highlights

Osteoarthritis (OA) is a chronic disease characterized by the progressive degeneration of cartilage that leads to joint pain and even serious disabilities of patients around the world [1, 2]
The transmission electron micrograph (TEM) showed that the amphiphilic polymer TKCP and TKCP@DEX could self-assemble into homogeneously spherical nanoparticles in aqueous solution (Fig. 1a and b)
Dynamic light scattering (DLS) analysis revealed that the average diameter of TKCP NPs was ~ 60 nm (Fig. 1c)

Summary

Introduction

Osteoarthritis (OA) is a chronic disease characterized by the progressive degeneration of cartilage that leads to joint pain and even serious disabilities of patients around the world [1, 2]. Endogenous-based fluorescent probes relying on certain physiological markers like NO [4] and MMP-13 [5,6,7,8] to generate fluorescence have been explored for detection of OA in vivo. These probes depending on pathological events are limited in clinical applications mainly due to the relatively low concentrations of endogenous biochemical markers [9,10,11,12], resulting in inaccurate and insensitive signals in the deep tissues.

Methods

Results

Conclusion