Self‐Cycling Free Radical Generator from LDH‐Based Nanohybrids for Ferroptosis‐Enhanced Chemodynamic Therapy

Abstract

Nonapoptotic ferroptosis has been a novel form of programmed cell death, which provides a new solution to enrich the anticancer treatment efficacy of traditional apoptotic therapeutic modality. Herein, a novel nanohybrid is designed by loading the PEG-encapsulated Artemisinin (denoted as A@P) on the ultrathin MgFe-LDH nanosheets (denoted as uLDHs) for improved chemodynamic therapy (CDT). The A@P/uLDHs cannot only realize the self-assembly between the Art and carrier but also be regarded as free radical generator. A comprehensive mechanistic study suggests that this unique A@P/uLDHs is able to in situ activate Art and self-cycling generate toxic C-centered free radical inside the cancer cells, without depending on abundant H 2 O 2 , accompanied with diminished cancerous antioxidation by depleting glutathione (GSH). The accumulation of ROS and depletion of GSH can further oxidize unsaturated fatty acid to generate lipid peroxide, whose overexpression can induce cell ferroptosis accompanied by cellular iron homeostasis turbulence. Both in vitro and in vivo results exhibit that A@P/uLDHs are an efficient nanoagent for highly efficient ferroptosis-enhanced CDT treatment. This work imparts the promising new visions about the ferroptosis-enhanced CDT via fine regulation of material design for improved cancer treatments.

Ultrathin Nanosheet-Supported Ag@Ag2O Core–Shell Nanoparticles with Vastly Enhanced Photothermal Conversion Efficiency for NIR-II-Triggered Photothermal Therapy

“…Ultrathin CoFeLDH-supported Ag@Ag 2 O core–shell nanoparticles (Ag@Ag 2 O/LDHs-U) with high monodispersity were successfully obtained through in situ spontaneous deposition of heterogeneous Ag@Ag 2 O nanoparticles onto ultrathin CoFeLDH (LDHs-U) supports (see Scheme and the SI). The ultrathin CoFeLDH supports with a Co/Fe proportion of ∼2 were synthesized via a modified solvent-free bottom-up approach reported previously . The X-ray diffraction pattern (XRD) of LDHs-U (Figure S1a) displayed a series of diffraction peaks at 11.5, 23.5, 34.6, 60.3, and 61.9°, which can be attributed to the characteristic peaks of the CoFe-CO 3 2– -LDHs phase .…”

“…The ultrathin CoFeLDH supports with a Co/Fe proportion of ∼2 were synthesized via a modified solvent-free bottom-up approach reported previously. 25 The X-ray diffraction pattern (XRD) of LDHs-U (Figure S1a) displayed a series of diffraction peaks at 11.5, 23.5, 34.6, 60.3, and 61.9°, which can be attributed to the characteristic peaks of the CoFe-CO 3 2− -LDHs phase. 26 The TEM image showed a typical nanosheet morphology for LDHs-U (Figure 1A), and dynamic lighting scatting (DLS) revealed their mean lateral size of ∼122 ± 78 nm and ζ potential of +31.8 mV (in the inset of Figures 1A and S2).…”

Strategies for enhancing cancer chemodynamic therapy performance

“…AFeNPs@CAI CDT MDA-MB-231 [35] FePt@FeOx@TAM-PEG CDT 4T1 [43] UCNP@PVP@MIL88B CDT U87MG [44] H 2 O 2 generation PTCG (EGCG, Pt-OH, PEG-b-PPOH) CDT/Chemotherapy HepG2 [17] Copper hexacyanoferrate CDT 4T1 [40] Den-DOX-Fe 3+ -TA CDT/Chemotherapy U14 [45] PGC-DOX (PEG-GOx, CaCuP, DOX) CDT/Chemotherapy 4T1 [46] ACC@DOX•Fe 2+ -CaSi-PAMAM-FA/mPEG CDT/Chemotherapy A375, 4T1 [47] (MSNs@CaO 2 -ICG)@LA CDT/PDT MCF-7 [48] PZIF67-AT CDT 4T1 [49] Copper peroxide nanodots CDT U87MG [50] GSH depletion FA-Pyrite CDT CT26 [34] MMDM (microphage, MCN, DOX, MnO 2 ) CDT/Chemotherapy 4T1 [51] A@P/uLDHs (artemisinin, PEG, MgFe-LDH) CDT HeLa [52] CCMZ (Cu, CuMoO x , ZP) CDT 4T1 [53] JNP Ve (Au-MnO JNPs, IR1061) CDT/Radiotherapy MCF-7 [54] DMON@Fe 0 /AT CDT 4T1 [55] CMBP (CuO/MnO x @BSA, Pt(IV) prodrug) CDT/Chemotherapy 4T1 [56] Zn x Mn 1−x S/PDA CDT/PTT 4T1 [57] PtCu 3 nanocage CDT/SDT 4T1 [58] External stimuli Light DGU:Fe/Dox CDT/Chemotherapy 4T1 [59] LET-6 (tPy-Cy-Fe, DSPE-PEG) CDT/PTT U87MG [60] GNR@SiO 2 @MnO 2 CDT/PTT U87MG [61] SnFe 2 O 4 nanozyme CDT/PTT/PDT 4T1 [62] MoSe 2 /CoSe 2 @PEG CDT/PTT H-22 [63] HULK (liposome, laccase, MOHQ, FeCe6) CDT 4T1 [64] Cu-OCNP/Lap CDT/PTT HeLa [65] AuPd@Fe x O y CDT/PTT A549 [66] Fe-doped MoO x nanowires CDT/PTT HeLa [67] Hollow magnetite nanoclusters CDT/PTT HeLa [68] ICG@Mn/Cu/Zn-MOF@MnO 2 CDT/PTT/PDT U87 [69] Wesselsite (SrCuSi 4 O 10 ) nanosheets CDT/PTT/Starvation therapy 4T1 [70] MoP 2 nanorods CDT/PTT CAL27 [71] X-ray Cu 2 (OH)PO 4 @PAAS CDT/Radiotherapy HeLa [72] CoFe 2 O 4 nanoparticles CDT/Radiotherapy MCF-7…”

“…Such strategies can be roughly outlined into TME modulation, usage of external stimuli, utilization of chemical and biological stimuli, and design of the nanoplatforms (Table 1). [ 16,17,22,34–36,40,43–105 ]…”

Bioinspired Construction of an Enzyme-Mimetic Supramolecular Nanoagent for RNS-Augmented Cascade Chemodynamic Therapy

“…LDHs are a kind of layered hydroxides composed of two or more metal ions, which are often used as a supramolecular host with the anion intercalation , and confinement effect . In addition, as a kind of solid base, LDHs have a good pH response . Herein, a supramolecular nanoagent was therefore designed and synthesized, which is SNP-intercalated MgMnFe-LDHs (denoted as S2MFL) and can be a candidate with RNS and ROS vectors for synergistic CDT, as shown in Scheme .…”