Engineering Oxygen‐Irrelevant Radical Nanogenerator for Hypoxia‐Independent Magnetothermodynamic Tumor Nanotherapy

Abstract

Tumor hypoxia substantially lowers the treatment efficacy of oxygen‐relevant therapeutic modalities because the production of reactive oxygen species in oxygen‐relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen‐irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer‐cell apoptosis in vitro and tumor suppression in vivo. Free‐radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co‐doped nanoparticles (MnFe2O4@CoFe2O4, denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen‐irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer‐cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen‐irrelevant nanoplatform for AMF‐initiated synergistic cancer treatment.

Natural Killer Cell Membrane‐Cloaked Virus‐Mimicking Nanogenerator with NIR‐Triggered Shape Reversal and •C/•OH Storm for Synergistic Thermodynamic–Chemodynamic Therapy

“…[ 16 ] Under thermal triggering, AIPH can be rapidly decomposed to produce toxic alkyl radical (•C) to kill cancer cells by directly oxidizing cellular substances or augmenting intracellular lipid hydroperoxides. [ 17 , 18 ] However, the AIPH is thermally unstable and the free radical production efficiency is highly dependent on the temperature in biological environment, it urgently needs to engineer a heat producer to control •C generation at tumor sites.…”

A Facile Nanoimpregnation Method for Preparing Paper‐Based Sensors and Actuators

“…[ 1–3 ] The use of fillers together with a cellulosic paper network can result in unique features which are not available in its pristine form, such as magnetic response. [ 4–7 ] Thus, the magnetic paper will exhibit the inherent properties of paper fibers and the magnetic properties of nanoparticles, allowing the obtention of valuable documents such as banknotes, bank checks, identity cards, and passports with improved security requirements. [ 8,9 ] In addition to these examples related to security papers, magnetic papers are also of interest due to their potential applications in electromagnetic shielding, information storage, magnetic filtering, magnetographic printing, textronic, loudspeaker membranes, flexible data storage, toxic waste remediation, membrane filtration/purification, point‐of‐care microfluidic devices, and magnetomechanical actuators.…”

Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging

“…175,176 Compared with MHT, MTDT can effectively overcome the defect of poor therapeutic effect due to the low magnetic and thermal conversion effect of MNPs in deep diseases, thus showing better therapeutic efficiency in the treatment of diseases. 26,177 The free radicals and magnetic heat generated in the process of MTDT complement each other. On the one hand, magnetic heat activates the generation of free radicals, and on the other hand, the generated free radicals can further promote the killing of pathological cells by magnetic heat.…”

“…Meanwhile, the use of nanocarriers for the delivery of chemical radiosensitizers not only can overcome the obstacle of the undesirable pharmacokinetics of these organic molecules, but also improve their drug bioavailability and targeting, greatly reducing their potential toxicities. 152 The use of carriers to introduce therapeutic radioisotopes (e.g., 211 At, 212 Bi, 213 Bi, 223 Ra, 225 Ac, 32 P, 89 Sr, 90 Y, 131 I, 166 Ho, 177 Lu, 67 Ga, 111 In, 123 I, 125 I, and 201 Tl) in cancer patients, which release a-particles, b-particles or Auger electrons to exterminate tumors, is also a reliable treatment for cancer. 153 Precise delivery of radioisotopes to tumor sites to optimize the radiation dose of tumors relative to normal organs is the key to improving RT, where nanomaterials can selectively deliver radioisotopes to tumor sites, significantly improving their bioavailability and minimizing their toxicity to healthy tissues.…”