In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets in Tumor-Microenvironment for Intensive Photothermal-Enhanced Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for ·OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.

Multivalence Manganese Mediated Dual ROS Generator for Augmented Chemodynamic Therapy and Activated Antitumor Immunogenic Responses

“…The XPS elemental valence analyses show that the Pt element exists in the form of Pt 0 , while the Mn element exists in the form of Mn 2+ (45.1%, 641.0 eV), Mn 3+ (35.0%, 642.8 eV), and Mn 4+ (19.9%, 646.0 eV) (Figure g and Figure S4). This existence of Mn 3+ and Mn 2+ ions offers the potential for the synchronous generation of 1 O 2 and ·OH by MnPt. , In this case, we chose 1,3-diphenylisobenzofuran (DPBF) as the probe to assess 1 O 2 generation. The UV–Vis spectra indicate that the characteristic peak of DPBF gradually reduces with the decrease of pH value in the presence of MnPt, while no change could be observed without MnPt (Figure h and Figure S5).…”

“…This existence of Mn 3+ and Mn 2+ ions offers the potential for the synchronous generation of 1 O 2 and •OH by MnPt. 22,37 In this case, we chose 1,3-diphenylisobenzofuran (DPBF) as the probe to assess 1 O 2 generation. The UV−Vis spectra indicate that the characteristic peak of DPBF gradually reduces with the decrease of pH value in the presence of MnPt, while no change could be observed without MnPt (Figure 1h and Figure S5).…”

Synthesis of 20-nm-sized CoAl-LDH nanoparticles modified with folic acid for enhanced cancer cell targeting

“…4 Nanomaterials that quickly dissolve and release these non-ferrous transition metals are especially attractive because they exhibit additional advantages to enhance the effect of CDT by increasing the sensitivity of cancer cells toward the oxidation, through the depletion of glutathione (GSH). 3,[5][6][7][8][9][10] Layered double hydroxides (LDHs) possess a general formula of…”

“…The use of nanometric LDHs, especially nanosheets, with a highly exposed surface is a topic of growing interest because of their quick response to the tumor microenvironment. For example, CoMn-LDH ultrathin nanosheets, 7,13 MgFebased LDH nanohybrids, 14 Ce-doped CuAl LDH nanosheets, 15 CuFe-LDH nanosheets, 16 and MnMgFe-LDH nanocomposites, 17 and FeMn LDH nanosheets 18 were demonstrated to provide abundant reactive sites to accelerate heterogeneous Fenton-like reactions as well as GSH depletion.…”