Polytonic Drug Release via Multi‐Hierarchical Microstructures Enabled by Nano‐Metamaterials

Abstract

″Nano‐metamaterials″, rationally designed novel class metamaterials with multilevel microarchitectures and both characteristic sizes and whole sizes at the nanoscale, are introduced into the area of drug delivery system (DDS), and the relationship between release profile and treatment efficacy at the single‐cell level is revealed for the first time. Fe3+‐core‐shell‐corona nano‐metamaterials (Fe3+‐CSCs) are synthesized using a dual‐kinetic control strategy. The hierarchical structure of Fe3+‐CSCs, with a homogeneous interior core, an onion‐like shell, and a hierarchically porous corona. A novel polytonic drug release profile occurred, which consists of three sequential stages: burst release, metronomic release, and sustained release. The Fe3+‐CSCs results in overwhelming accumulation of lipid reactive oxygen species (ROS), cytoplasm ROS, and mitochondrial ROS in tumor cells and induces unregulated cell death. This cell death modality causes cell membranes to form blebs, seriously corrupting cell membranes to significantly overcome the drug‐resistance issues. It is first demonstrated that nano‐metamaterials of well‐defined microstructures can modulate drug release profile at the single cell level, which in turn alters the downstream biochemical reactions and subsequent cell death modalities. This concept has significant implications in the drug delivery area and can serve to assist in designing potential intelligent nanostructures for novel molecular‐based diagnostics and therapeutics.

Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging

“…Enhancing the ferroptosis catalytic process of iron oxide MNPs in the TME has been one of the main strategies for the ferroptosis cancer nanomedicine. Various types of iron oxide MNPs such as anisotropic, porous, or hierarchical morphologies have been studied for the multifunctional ferroptosis nanomedicine agents [ 103 , 216 , 217 ]. Forming a hybrid MNP nanostructures composed of iron oxide MNPs and other transition metal oxides also provides a strategy to sustain the multivalent metal ion redox cycle [ 218 , 219 ].…”

Tailored Drug Delivery Platforms: Stimulus‐Responsive Core–Shell Structured Nanocarriers

“…[ 21 ] On this basis researchers aiming to utilize pores as sites for drug loading have designed a series of drug delivery tools built on pore structured core–shell vehicles. The core portions allow several responsive species, such as magnetically responsive Fe 2 O 3 ; [ 22 ] Au NPs with photothermal conversion capabilities and polydopamine (PDA) NPs possess the ability to be highly modifiable. [ 23,24 ] Conversely, the choice of the corresponding external material (shell counterparts) has gained new advancements in recent years.…”

Engineering a pH‐responsive polymeric micelle co‐loaded with paclitaxel and triptolide for breast cancer therapy

“…In recent years, the rise of nanotechnology has facilitated the development of nanodrug delivery systems (NDDS). NDDS provides a promising method for controlled and targeted drug delivery due to its good biocompatibility, 17 low side effects, 18 targeting, 19 and controlled release, 20 and is one of the prospective strategies for cancer therapy. 21 , 22 , 23 NDDS include nanoparticles, liposomes, polymeric micelles, polymeric drug couplers, etc.…”