Nanoscale Micelles Loaded with Fe₃O₄ Nanoparticles for Deep-Tissue Penetration and Ferroptosis/Sonodynamic Tumor Therapy

Abstract

Large nanoparticles (NPs; >100 nm) can accumulate in the tumor because of the enhanced permeation and retention effect. However, large NPs generally locate next to the blood vessel and are difficult to diffuse within a dense collagen matrix, causing uneven distribution within the tumor. Here, we designed reversibly assembled and disassembled micelles loaded with Fe 3 O 4 and hypocrellin (HC) for ferroptosis and sonodynamic therapy of cancer. Poly(ethylene glycol)−poly(propylene sulfide) (PEG−PPS), an reactive oxygen species (ROS)-responsive amphiphilic polymer, was used to form micelles with Fe 3 O 4 and HC in the core. Upon ultrasound irradiation, ROS was generated by HC for the disassembly of micelles and also for sonodynamic therapy, while realizing a size switch. The released Fe 3 O 4 dissolves to produce Fe 2+ , which catalyzes hydrogen peroxide to form hydroxyl radicals ( • OH). Sonodynamic and ferroptosis therapies generate a synergistic antitumor effect, offering a smart platform for cancer therapy.

Tumor‐targeted and microenvironment‐activatable iron‐based nMOF for synergistic inducing ferroptosis

“…25 Metal-organic frameworks (MOFs) have the advantages of large pore volume and high specific surface area, the ability to introduce functional groups on the surface by post-modification method, and good biodegradability compared with the traditional nano drug carriers. [26][27][28] Certain iron-based MOFs not only have the above advantages but also release iron ions to promote ferroptosis triggered by iron overload in the microenvironment of tumor cells, making them an ideal drug-carrying nanomaterial. 29,30 On the basis of the above background, we successfully constructed the Sora-loaded nanoparticles SM@F by loading Sora into the cage structure of iron-based nMOF (MOF) and modifying the surface with tumour-targeted molecular folic acid (FA).…”

“…Metal–organic frameworks (MOFs) have the advantages of large pore volume and high specific surface area, the ability to introduce functional groups on the surface by post‐modification method, and good biodegradability compared with the traditional nano drug carriers 26–28 . Certain iron‐based MOFs not only have the above advantages but also release iron ions to promote ferroptosis triggered by iron overload in the microenvironment of tumor cells, making them an ideal drug‐carrying nanomaterial 29,30 …”

Efficient Strategy to Synthesize Tunable pH-Responsive Hybrid Micelles Based on Iron Oxide and Gold Nanoparticles

“…Lipid-based formulations, such as liposomes and micelles, are other important and well-known formulations for the preparation of hybrid nanomaterials with high potential to enter in clinical trials or even to be approved for clinic. , Several groups have reported effective synthesis of magneto liposomes for in vivo applications. − The utilization of liposomes enables the incorporation of a sufficient amount of magnetic NPs within the membrane or the lumen of the liposomes. On the other hand, micelles have been reported as promising nanoformulations to carry inorganic NP payloads due to their smaller sizes than other lipid-based nanomaterials, ease of chemical modifications of the amphiphiles, and excellent pharmacokinetics. − The incorporation of stimuli-response functionality into the organic material is another key factor in the preparation of hybrid nanomaterials. − These functions are triggered in response to external stimuli, such as pH, temperature, or redox conditions. Overall, pH change is one of the most widely investigated stimuli for biomedical applications.…”

Molecular Sonosensitizer-Loaded Polymer Nanomicelle for Ultrasound-Based Cell Therapy via Singlet Oxygen Generation

“…However, there is no general agreement of such a mechanism, and in most cases, singlet oxygen has been observed as the main contributors among all other types of reactive oxygen species (ROS) . In most of the applications, molecular sonosensitizers are combined with microbubbles or other sonosensitizer nanoparticles to enhance the therapeutic performance. − …”