Oxygen Self‐Supply Engineering‐Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy

Abstract

to perform PDT. [7] PSs absorb laser energy in the presence of O 2 to produce cytotoxic reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) that causes the destruction of the genetic material in cancer cells, leading to cell apoptosis, or necrosis. [7][8][9][10] The O 2 involved in PDT improves tumor destruction and reduces the toxic side effects as compared with other conventional therapeutic modalities like radiotherapy, chemotherapy, and surgery. [11][12][13][14][15] However, hypoxia, one of the hallmarks of malignant tumors, [16][17][18] induces an unexpected resistance of tumors to PDT, since molecular O 2 plays an essential role during the process. Some types of nanocatalysts have been used to address this dilemma, such as manganese dioxide (MnO 2 ) nanoparticles, carbon dot, and single-atom ruthenium (Ru) for an in situ catalysis of the decomposition of H 2 O 2 to generate O 2 . [6,14,19] This could be an effective strategy to relieve hypoxia in the tumor microenvironment (TME), thus becoming a potential approach to improve the efficacy of PDT. [20] Additionally, the acidic TME with an excessive amount of H 2 O 2 is a natural activator of these nanocatalysts, making them intelligent nanocatalysts for tumor specific therapy. [21][22][23] Recently, MnO 2 nanostructures have received extensive attention in the field of bio-applications for their efficient O 2 production and easy synthesis, [24][25][26][27] enhancing the effect of radiation therapy, [27] chemotherapy, [28] and PDT. [29] In addition, MnO 2 is rapidly decomposed into water soluble Mn 2+ ion in an acidic condition, [6,[30][31][32][33][34] and excreted through the bile into the feces, avoiding unexpected accumulation and long-term toxicity in vivo. [6,29] However, MnO 2 nanostructures without surface coating have a poor structure stability under physiological conditions, [35] and it is difficult to control their size and morphology during the synthesis, thus, increasing the uncertainty of the reactivity of the nanomaterial. [25] Therefore, it is highly desirable to construct MnO 2 nanoparticles with uniform morphology, high stability and biocompatibility for biomedical applications.Ferritin (Ftn) is an endogenous iron storage protein composed of 24 subunits, with a hollow structure of 12 nm in the external diameter and an inner cavity of 8 nm. [36] Ftn has been widely used as a superior protein nanocage for the Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes tumor development and metastasis. Photodynamic therapy (PDT) is a promising strategy in the treatment of tumors, but it is limited by the lack of oxygen in TME. In this work, an O 2 self-supply PDT system is constructed by co-encapsulation of chlorin e6 (Ce6) and a MnO 2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/ Ftn@MnO 2 ) for tumor therapy. Ce6/Ftn@MnO 2 exhibits a uniform small size (15.5 nm) and high stability due to the inherent structure of Ftn. The fluorescence imaging and immunofluorescence analysis dem...

Nanozymes for Regenerative Medicine

“…Co-encapsulation of Ce6 and MnO 2 nanozymes in ferritin (Ce6/Ftn@MnO 2 ) Photodynamic therapy for hypoxia tumors and MRI imaging [89] Targeted binding to TfR1 receptors on tumors, prolonged blood circulation time, deep tumor tissue penetration, and biosafety Human heavy chain ferritin (FTn) loading Pt, Rh, Au, Ir, and Mn, respectively (FTn-Pt, FTn-Rh, FTn-Au, FTn-Ir, and FTn-Mn)…”

“…These beneficial properties in vivo provide a reliable basis to perform the cascade catalytic reaction via co‐delivering in nanozyme and natural GOx by liposomes to increase therapeutics effects. [ 89 ]…”

The application of photodynamic therapy in plastic and reconstructive surgery

“…Pro. Liu constructed an O 2 self-supply PDT system by co-encapsulation of chlorin e6 (Ce6) and a MnO 2 core in an engineered ferritin (Ftn), generating a nanozyme promoted PDT nanoformula (Ce6/Ftn@MnO 2 ) for tumor therapy (Zhu et al, 2022). This method enhanced the effectiveness and precision of PDT by TME modulation (Figure 3C).…”

Injectable agarose hydrogels and doxorubicin-encapsulated iron-gallic acid nanoparticles for chemodynamic-photothermal synergistic therapy against osteosarcoma

“… Zhu et al, 2021 ; Y. Zhu et al, 2020 ; Y. Zhu et al, 2022 ; W. Wang et al, 2021 ). Herein, we first synthesised uniform iron–GA (FeGA) and constructed an agarose hydrogel (AG)-encapsulated iron–GA decorated with doxorubicin (FeGA-DOX) nanoplatforms for the treatment of osteosarcoma.…”