PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer

Abstract

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system.

Nanomaterials as Theranostic Agents for Cancer Therapy

“…This, in turn, promoted the Fenton reaction by FePt alloys, enhancing the accumulation of reactive oxygen species (ROS) within the cells. Further, the elevated oxidative stress and acidity within the cells triggered the release of a significant quantity of Pt­(II) ions from the FePt alloys, contributing to cancer chemotherapy . Chitosan is used as the capping agent in many alloys and bimetallic NPs.…”

“…Further, the elevated oxidative stress and acidity within the cells triggered the release of a significant quantity of Pt(II) ions from the FePt alloys, contributing to cancer chemotherapy. 173 Chitosan is used as the capping agent in many alloys and bimetallic NPs. It facilitates the bioconjugation of DOX on the surface of AgGd BNPs.…”

Imaging‐Guided Cancer Therapy Based on Multifunctional Magnetic Nanoparticles†

“…The HMFe demonstrated prominent T 2 ‐weighted MRI performance thus MM@HMFe@ BS could be employed for MRI‐guided CDT, monitoring the bio‐distribution and treatment progress of agents. Notably, some other MNPs such as FeS, [ 30,75 ] FePt, [ 76 ] and FePd [ 77 ] have also been reported for T 2 ‐weighted MRI‐guided CDT.…”

Prussian Blue-Derived Nanoplatform for In Situ Amplified Photothermal/Chemodynamic/Starvation Therapy

“…It is apparent from the above reaction that GOx can further increase the TME acidity and H 2 O 2 levels in addition to consuming glucose. , The advantages of starvation therapy-assisted CDT are apparent; that is, in addition to terminating glucose, which is a key energy supplier for the tumor growth metabolism, the accompanying increase in acidity enhances the catalytic efficiency of the acid-dependent Fenton or Fenton-like reaction and compensates for the deficiency in endogenous H 2 O 2 content.…”