Polypyrrole Nanoenzymes as Tumor Microenvironment Modulators to Reprogram Macrophage and Potentiate Immunotherapy

Abstract

Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years, but its therapeutic outcome is drastically diminished by species of nanozyme, concentration of substrate, pH value, and reaction temperature, etc. Herein, a novel Cu‐doped polypyrrole nanozyme (CuP) with trienzyme‐like activities, including catalase (CAT), glutathione peroxidase (GPx), and peroxidase (POD), is first proposed by a straightforward one‐step procedure, which can specifically promote O 2 and ·OH elevation but glutathione (GSH) reduction in tumor microenvironment (TME), causing irreversible oxidative stress damage to tumor cells and reversing the redox balance. The PEGylated CuP nanozyme (CuPP) has been demonstrated to efficiently reverse immunosuppressive TME by overcoming tumor hypoxia and re‐educating macrophage from pro‐tumoral M2 to anti‐tumoral M1 phenotype. More importantly, CuPP exhibits hyperthermia‐enhanced enzyme‐mimic catalytic and immunoregulatory activities, which results in intense immune responses and almost complete tumor inhibition by further combining with α PD‐L1. This work opens intriguing perspectives not only in enzyme‐catalytic nanomedicine but also in macrophage‐based tumor immunotherapy.

Messenger Nanozyme for Reprogramming the Microenvironment of Rheumatoid Arthritis

“…58 As artificial enzymes, nanozymes are more tolerant to harsh environments, more durable, and less costly than natural enzymes. 59 More importantly, their catalytic activity can be regulated by artificial means such as surface modification and size control. 60 Some endogenous stimuli such as pH and redox, and exogenous stimuli such as light, temperature, and ultrasound can also be utilized as triggers to control the activation and enhancement of the nanozyme.…”

“…Many nanomaterials are mainly transition metal-based nanomaterials such as iron-based, copper-based, manganese-based, nickel-based, and cerium-based nanomaterials, and they have been revealed to possess one or more enzyme-like activities such as CAT, POD, SOD, and glutathione peroxidase (GPx) because the metal active centers can effectively mimic the catalytic electronic redox process achieved by natural enzymes . As artificial enzymes, nanozymes are more tolerant to harsh environments, more durable, and less costly than natural enzymes . More importantly, their catalytic activity can be regulated by artificial means such as surface modification and size control .…”

Progress and prospects of nanozymes for enhanced antitumor therapy

“…With the reversion of hypoxic microenvironment, macrophages in tumor site were repolarized from pro-tumoral M2 to antitumoral M1 phenotype, accompanied by the upregulation of IL-12 and the downregulation of IL-10. Moreover, the ratio of CD4 + and CD8 + T cells was elevated by further combining with αPD-L1, exhibiting strong immune responses (Zeng et al, 2022b). Except for αPD-L1, the synergistic effect is also achieved by combining with CTLA-4 blockade.…”

A bimodal type of AgPd Plasmonic Blackbody Nanozyme with boosted catalytic efficacy and synergized photothermal therapy for efficacious tumor treatment in the second biological window

“…On the other hand, this also provides opportunities to alleviate hypoxia and produce reactive oxygen species (ROS), such as hydroxyl radicals (•OH), for effective tumor treatment through nanocatalytic activities-chemodynamic therapy (CDT) using enriched H 2 O 2 [21][22][23][24][25]. A great deal of effort has been taken to explore the utilization of nanozyme for catalytic tumor therapy [26][27][28][29][30][31][32][33][34], which, however, was confined by the low catalytic efficiencies.…”