Bioinspired "Active" Stealth Magneto-Nanomicelles for Theranostics Combining Efficient MRI and Enhanced Drug Delivery

The mononuclear phagocyte system (MPS) with key roles in recognition and clearance of foreign particles, is a major constraint to nanoparticle-based delivery systems. The desire to improve the delivery efficiency has prompted the search for stealthy long-circulating nanoplatforms. Herein, we design an antiphagocytic delivery system with "active" stealth behavior for cancer theranostics combining efficient MRI and enhanced drug delivery. We modify self-peptide, a synthetic peptide for active immunomodulation, to biodegradable poly(lactide-glycolide)-poly(ethylene glycol) (PLGA-PEG), then utilize the self-assembly properties of PLGA-PEG to form nanomicelles that encapsulating iron oxide (IO) nanoparticles and anticancer drug paclitaxel (PTX). Through the interaction of self-peptide with the receptor SIRPα, which is expressed on phagocytes, the as-prepared nanomicelles can disguise as "self" to avoid being recognized as foreign particles by MPS, leading to improved blood circulation time and delivery efficiency. Compared to the "passive" stealth effect generating by PEG or zwitterionic polymers that only passively delay the physisorption of serum proteins to nanocarriers, the "active self" nanomicelles can more efficiently inhibit the MPS-mediated immune clearance and reduce "accelerated blood clearance" phenomenon. Furthermore, this one-step clustering of IO nanoparticles and loading of PTX endow the resulted magneto-nanomicelles with enhanced T₂ MRI contrast performance and antitumor effect. We believe that this study provides a novel approach in designing of efficient stealth antiphagocytic delivery systems that resisting the MPS-mediated clearance for cancer theranostics.