Charge‐Reversal Polymer Nano‐modulators for Photodynamic Immunotherapy of Cancer

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(35), P. 19355 - 19363

Published: June 9, 2021

Nanomedicine can regulate the balance between cytotoxic T lymphocytes (CTLs) and suppressive regulatory (Tregs), which however has been rarely exploited for cancer immunotherapy. We report a charge-reversal polymer nano-modulator (SPDMC N) activated by tumor microenvironment (TME) photodynamic immunotherapy of cancer. SPDMC N is constructed conjugating an immunomodulator (demethylcantharidin, DMC) to side chains via acid-liable linker. The negative charge ensures its high stability in blood circulation ideal accumulation; exposure acidic TME reverses surface positive, enhancing penetration locally releasing DMC. Upon near-infrared photoirradiation, generates singlet oxygen ablate tumors promote maturation dendritic cells. Released DMC inhibits protein phosphatase 2 (PP2A) activity decreases Tregs differentiation. Such combinational action induces sharp increase CTL/Treg ratio effectively both primary distant living mice.

Language: Английский

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Constructing Electron Levers in Perovskite Nanocrystals to Regulate the Local Electron Density for Intensive Chemodynamic Therapy

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(16), P. 8905 - 8912

Published: Feb. 4, 2021

Abstract The local electron density of an atom is one key factor that determines its chemical properties. Regulating can promote the atom's reactivity and so reduce reaction activation energy, which highly desired in many applications. Herein, we report intra‐crystalline lever strategy, regulate centre atoms via manipulating ambient lattice states, for Fenton activity improvement. Typically, with assistance ultrasound, Mn 4+ −O−Fe 3+ bond BiFe 0.97 0.03 O 3 perovskite nanocrystals drive valence electrons free to accumulate on Fe by a polarization electric field originated from designed strain. increase significantly improves catalytic Fe, decreasing energy ‐mediated 52.55 %, increasing . OH yield 9.21‐fold. This study provides new way understand sono‐Fenton chemistry, increased production enables effective chemodynamic therapy.

Language: Английский

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Complementing Cancer Photodynamic Therapy with Ferroptosis through Iron Oxide Loaded Porphyrin-Grafted Lipid Nanoparticles

ACS Nano, Journal Year: 2021, Volume and Issue: 15(12), P. 20164 - 20180

Published: Dec. 13, 2021

Nanomaterials that combine multimodality imaging and therapeutic functions within a single nanoplatform have drawn extensive attention for molecular medicines biological applications. Herein, we report theranostic based on relatively smaller (<20 nm) iron oxide loaded porphyrin-grafted lipid nanoparticles (Fe3O4@PGL NPs). The amphiphilic PGL easily self-assembled the hydrophobic exterior surface of ultrasmall Fe3O4 NPs, resulting in final Fe3O4@PGL NPs with diameter ∼10 nm. excellent self-assembling nature as-synthesized facilitated higher loading porphyrins, showed negligible dark toxicity, demonstrated an photodynamic effect against HT-29 cancer cells vitro. vivo experimental results further confirmed were ideally qualified both fluorescence magnetic resonance (MR) guided nanoplatforms to track biodistribution responses as well simultaneously trigger generation highly cytotoxic reactive oxygen species (ROS) necessary therapy (PDT). After recording convincing responses, evaluated ability NPs/Fe3O4@Lipid ferroptosis (FT) via tumor microenvironment (TME) modulation improved anticancer activity. We hypothesized tumor-associated macrophages (TAMs) could significantly improve efficacy FT by accelerating Fenton reaction In our results, Fe ions released vitro directly contributed reaction, whereas presence RAW 264.7 accelerated ROS observed imaging. significant increase during coincubation endocytosed RAW264.7 cells, induced increased cellular toxicity cells.

Language: Английский

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Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 22, 2021

Abstract Tumor response to radiotherapy or ferroptosis is closely related hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring therapy, but challenging. Here, we report the optimization a diene electrochromic material (1-Br-Et) as •OH-responsive chromophore, and use it develop near-infrared ratiometric fluorescent photoacoustic (FL/PA) bimodal probe for vivo •OH. The displays large FL ratio between 780 1113 nm (FL /FL ), small PA 755 905 (PA /PA ). Oxidation 1-Br-Et by decreases while concurrently increasing , allowing reliable production undergoing erastin-induced radiotherapy.

Language: Английский

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Dual key co-activated nanoplatform for switchable MRI monitoring accurate ferroptosis-based synergistic therapy

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1956 - 1981

Published: March 28, 2022

Language: Английский

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