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

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 (TP) developed by us via a ROS sensitive bond to form a diagnosis-therapy compound TPP, 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 TPP. Then the ROS responsive bond in TPP is subsequently broken, resulting in the accurate delivery of Pred and the inflammation therapy. Furthermore, TPP@PMM can be traced in vivo with a distinct two-photon imaging due to the AIE active fluorophore TP. 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.