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 (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.

Which is Better for Nanomedicines: Nanocatalysts or Single‐Atom Catalysts?

“…Ma et al developed nanoplatforms with serial ROS responsiveness and two-photon aggregation-induced emission (AIE) bioimaging for 3D diagnosis and accurate treatment of inflammation. [243] Prednisolone (Pred) was a widely used antiinflammatory glucocorticoid that bound to two-photon AIE fluo-rophase (TP) by ROS sensitive connections, forming a diagnosistherapeutic compound TPP. As a hydrophilic part, poly (2methyl-acrylloxyethyl phosphorylcholine) (PMPC), due to the presence of its amphoteric ion phosphorylcholine, had good stability in the process of blood transportation.…”

“…This strategy has been further applied to H 2 generation in pathological areas for antioxidant Adapted with permission. [243] Copyright 2020, American Chemical Society. c) BRSNPs for the experimental AP application.…”

“…Adapted with permission. [ 243 ] Copyright 2020, American Chemical Society. c) BRSNPs for the experimental AP application.…”

“…a) Illustration of developing a nanoplatform with two-photon imaging and serial ROS sensitivity. b) Photographs of the right hind limbs and H&E staining sections of joint tissue of arthritic mice with different formulations on day 27.Adapted with permission [243]. Copyright 2020, American Chemical Society.…”

ROS Responsive Nanoplatform with Two‐Photon AIE Imaging for Atherosclerosis Diagnosis and “Two‐Pronged” Therapy

“…Prednisolone (Pred), an anti‐inflammatory glucocorticoid used widely yet restrictively due to its poor solubility and severe side effect, [ 14 ] can be carried into the entocoele of CD by supramolecular interaction. [ 8b ] The two‐photon fluorophore‐cyclodextrin/prednisolone complexes (TPCDP) can be further packaged as the core into polymeric micelles based on amphiphilic poly (2‐methylthio ethanol methacrylate)‐poly (2‐methacryloyloxyethyl phosphorylcholine), (PMEMA‐PMPC, PMM) copolymer developed by us, [ 15 ] which can offer a favorable biocompatibility with few protein adsorption and impressive ROS triggered micellar disassembly. [ 16 ] The TPCDP@PMM micelles are expected to perform a stable transportation in blood circulation, which can finally accumulate at atherosclerotic lesions through the damaged vascular endothelium.…”