Nanoerythrocyte Membrane–Enveloped ROS‐Responsive 5‐Aminolevulinic Acid Prodrug Nanostructures with Robust Atheroprotection

Abstract

The development of smart nanoagents that can respond to a specific stimulus has gained remarkable interest for treating various kinds of diseases, including atherosclerosis. On the other hand, a cell camouflaging strategy has been considered as a pivotal factor to improve the delivery stealthiness, biocompatibility, and biodegradability of nanocarriers, resolving the shortcomings of PEGylation. In this study, reactive oxygen species (ROS)‐responsive 5‐aminolevulinic acid (ALA) prodrug nanostructures (ROSELLA) encapsulating rapamycin (RAP) are blended with nanoerythrocyte membranes to construct red blood cell membrane (RBCM)/RAP@ROSELLA. These nanoagents are designed to be able to escape the biological barriers, accumulate in atherosclerosis lesions, and enhance the release of drugs in the intracellular milieu due to the magnification of hydrogen peroxide (H2O2). In vitro study proves its superior ability to inhibit the proliferation of macrophages and vascular smooth muscle cells. In vivo developmental toxicity further confirms that no significant systematic toxicity is induced by RBCM/RAP@ROSELLA, implying its favorable biocompatibility, which has potential for precise nanomedicine to combat atherosclerosis.

Highly sensitive H2O2-scavenging nano-bionic system for precise treatment of atherosclerosis

“…The type of membrane proteins had no changes after coating on NPs in comparison to the erythrocyte membrane. In literature, the erythrocyte membrane made of ultrasonic method had verified that the membrane protein does not change after wrapping by SDS-PAGE gel electrophoresis 47 , 48 . The Results show that RP and RPP contained RBC membrane proteins ( Supporting Information Fig.…”

Recent Advances in ROS-Sensitive Nano-Formulations for Atherosclerosis Applications

“…After accumulation at the targeted inflammatory sites, anti-atherosclerotic drugs loaded in ROS-sensitive nanoparticles would be subsequently released responding to the high concentration level of ROS, thereby enabling effective drug therapy [ 99 ]. Moreover, in our previous study, a biomimetic and intelligent nanosystem was designed using ROS-responsive 5-aminolevulinic acid encapsulated with rapamycin, which were coated with a red blood cell membrane [ 101 ]. This biomimetic nano-formulation provided a feasible method to prevent the premature release of drugs during circulation, as well as break the shell in response to high H 2 O 2 exposure, thus having potential therapeutic effects toward atherosclerosis.…”

Biomedical Application of Reactive Oxygen Species–Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases

“…The small drug molecules or polymers can be built up into NPs with bottom-up methods, but the shape, size, and dispersity are not easily to control, while the top-down method can be used in the fabrication of NPs with well-controlled shape and uniform size (Chan and Kwok, 2011 ). Maruf et al ( 2020 ) fabricated red blood cell membrane–coated ROS-responsive 5-aminolevulinic acid prodrug nanostructures with robust atheroprotection using the top-down method.…”