Multivalent Polypeptide and Tannic Acid Cooperatively Iron-Coordinated Nanohybrids for Synergistic Cancer Photothermal Ferroptosis Therapy

Abstract

Owing to having a unique mechanism to kill cancer cells via the membrane accumulation of lipid peroxide (LPO) and the downregulation of glutathione peroxidase-4 (GPX-4), the ferroptosis therapy (FT) of tumors based on the Fenton reaction of iron nanoparticles has been receiving much attention in the past decade; however, there are some hurdles including the uncontrollable release of iron ions, slower kinetics of the intracellular Fenton reaction, and poor efficacy of FT that need to be overcome. Considering cooperative coordination of a multivalent thiol-pendant polypeptide ligand with iron ions, we put forward a facile strategy for constructing the iron-coordinated nanohybrid of methacryloyloxyethyl phosphorylcholine-grafted polycysteine/iron ions/tannic acid (i.e., PCFT), which could deliver a higher concentration of iron ions into cells. The dynamic and unsaturated coordination in PCFT is favorable for the intracellular stimuli-triggered release and fast Fenton reaction to realize efficient FT, while its intrinsic photothermia would boost the Fenton reaction to induce a synergistic effect between FT and photothermal therapy (PTT). Both immunofluorescence analyses of reactive oxygen species (ROS) and LPO confirmed that the intracellular Fenton reaction resulted in efficient FT, during which process the photothermia greatly boosted ferroptosis, and the Western blot assay corroborated that the expression level of GPX-4 was downregulated by FT and highly degraded by the photothermia to induce synergistic PTT-FT in vitro. Excitingly, by a single intravenous dose of PCFT plus one NIR irradiation, in vivo PTT-FT treatment completely eradicated 4T1 tumors without skin scar and tumor recurrence for 16 days, demonstrating prominent antitumor efficacy, as evidenced by the GPX-4, H&E, and TUNEL assays.

Natural polyphenol tannin-immobilized composites: rational design and versatile applications

“…Employing PTT technology, cancer therapy was realized using multivalent polypeptide and TA cooperatively iron-coordinated nanohybrids. 287…”

“…Employing PTT technology, cancer therapy was realized using multivalent polypeptide and TA cooperatively ironcoordinated nanohybrids. 287 Another compelling work done by Song et al 288 involved the use of polyphenol-based capsules for the intracellular delivery of antimicrobial peptide polymers, which could increase the therapeutic efficiency due to their reduced clearance, preventing peptide degradation and improving the intracellular delivery and dosage to the target host cells. In this work, two strategies were employed to fabricate the capsules (Fig.…”

Biocompatible Polymer‐Modified Nanoplatform for Ferroptosis‐Enhanced Combination Cancer Therapy

“…also put forward another facile strategy for constructing the iron‐coordinated nanohybrid of methacryloyloxyethyl phosphorylcholine‐grafted polycysteine/iron ions/tannic acid (i.e., PCFT). [ 62 ] The PCFT possessed intrinsic photothermia and the reductive iron content of ≈12.0 wt.%, which was favorable for realizing FT along with multiple imagings (Figure 8E,F), and in vivo PTT‐FT treatment eradicated 4T1 tumors without skin scar and tumor recurrence for 16 days (Figure 8G). Those studies open up an avenue to overcome the poor efficacy of monotherapy FT and mild PTT via the combo mild PTT‐FT treatment.…”

Injectable, antibacterial, and oxygen-releasing chitosan-based hydrogel for multimodal healing of bacteria-infected wounds

“…20 Among various metal ions, complexation of TA with Fe 3+ with low biotoxicity has received great attention. 22,23 Such organic-inorganic hybrid material has also exhibited excellent photothermal performance in the nearinfrared (NIR) region. 24 Chemodynamic therapy (CDT) is a promising approach to infection treatment.…”