Reactive Oxygen Species Responsive Theranostic Nanoplatform for Two-Photon Aggregation-Induced Emission Imaging and Therapy of Acute and Chronic Inflammation

Abstract

Inflammation is a protective response to stimuli trauma, which can also lead to severe tissue injury. The existing anti-inflammatory drugs, such as corticosteroids and glucocorticoids, generally exhibit side effects and poor accumulation in inflammatory tissue. Hence, a theranostic nanoplatform with serial reactive oxygen species (ROS) responsiveness and two-photon AIE bioimaging has been constructed for dimensional diagnosis and accurate therapy of inflammation. Prednisolone (Pred) is bridged to a two-photon fluorophore (<b>TP</b>) developed by us via a ROS sensitive bond to form a diagnosis-therapy compound <b>TPP</b>, which is then loaded by the amphipathic polymer PMPC-PMEMA (PMM) through self-assembling into the core-shell structured micelles (TPP@PMM). With a particle size of 57.5 nm, TPP@PMM can realize the accumulation in the inflammatory site via the oedematous tissue and the accurate release of anti-inflammatory drug Pred through the serial response to the local overexpressed ROS. The micellar structure is first interrupted by the ROS triggered hydrophobic-to-hydrophilic conversion of PMEMA, which allows the release of <b>TPP</b>. Then the ROS responsive bond in <b>TPP</b> is subsequently broken, resulting in the accurate delivery of Pred and the inflammation therapy. Furthermore, TPP@PMM can be traced <i>in vivo</i> with a distinct two-photon imaging due to the AIE active fluorophore <b>TP</b>. The theranostic TPP@PMM reveals high-resolution inflammation diagnosis and efficient anti-inflammatory activity owing to the two-photon fluorophore and the serial ROS responsiveness and has been proven to achieve the efficient treatment of acute lung injury, arthritis, and atherosclerosis. Therefore, TPP@PMM holds considerable promise as a potential strategy for acute and chronic inflammation theranostics.