Pd‐Single‐Atom Coordinated Biocatalysts for Chem‐/Sono‐/Photo‐Trimodal Tumor Therapies

Abstract

clinical cancer treatments. [1] Though some conventional methods, such as surgery, radiotherapy, and chemotherapy, have been used to treat malignant melanoma in clinics, these methods have exhibited limited treatment efficiencies in inhibiting tumor growth, leading to low patient survival rates. Therefore, more creative and efficient ways are urgently needed to overcome these clinical bottlenecks; for instance, gene therapy, photodynamic therapy (PDT), photothermal therapy, sonodynamic therapy (SDT), and immunotherapy. [2][3][4][5][6] However, due to the diversity, complexity, and heterogeneity of the MM tumor, [7] mono-modal therapy has been found to show limited treatment efficiency for MM tumors. Consequently, searching for integrated therapeutic strategies with multi-modal therapeutics is highly necessary to achieve remarkable antitumor effects. [8][9][10][11][12] The SDT and PDT have been selected as potential clinical methods for treating a wide range of superficial and localized tumors. They utilize the sono-irradiation or photoexcitation to generate highly reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ) and hydroxyl radicals (•OH). [13][14][15][16][17] Owing to the temporal and spatial management over the localization of the sound or light, the ROS can be generated precisely in the tumor tissues instead of normal tissue, thus minimizing the side effects. [18][19][20] The unique quantity of deep tissue penetration and little side The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono-modal treatment. Recently, multi-modal therapeutics with enhanced antitumor efficiencies have attracted increasing attention. However, designing a nanotherapeutic platform with uniform morphology in nanoscale that integrates with efficient chem-/sono-/phototrimodal tumor therapies is still a great challenge. Here, new and facile Pd-single-atom coordinated porphyrin-based polymeric networks as biocatalysts, namely, Pd-Pta/Por, for chem-/sono-/photo-trimodal tumor therapies are designed. The atomic morphology and chemical structure analysis prove that the biocatalyst consists of atomic Pd-N coordination networks with a Pd-N 2 -Cl 2 catalytic center. The characterization of peroxidase-like catalytic activities displays that the Pd-Pta/Por can generate abundant •OH radicals for chemodynamic therapies. The ultrasound irradiation or laser excitation can significantly boost the catalytic production of 1 O 2 by the porphyrin-based sono-/photosensitizers to achieve combined sono-/photodynamic therapies. The superior catalytic production of •OH is further verified by density functional theory calculation. Finally, the corresponding in vitro and in vivo experiments have demonstrated their synergistic chem-/sono-/photo-trimodal antitumor efficacies. It is believed that this study provides new promising single-atom-coordinated polymeric networks with highly efficient biocatalytic sites and synergistic trimodal therapeutic effects, which may inspire many new findings in rea...

Single‐Atom Nanozymes for Biomedical Applications: Recent Advances and Challenges

“…FeÀ NÀ C [26] FeN 3 P [27] Cu-HCF [28] Pd@ZIF-8 [29] Mn/PSAE [30] Pd [31] OxgeMCC-r [32] PMCS [33] FeÀ N x [34] Au/g-C 3 N 4 [35] Pt/CeO 2 [36] Au25 [37] FeÀ N 4 [38] Yan et al [43] also synthesized a single-atom Bi-anchored Au hydrogel (BiSA@Au) through a wet method. In this design, NaBH 4 was added to the precursor solution of HAuCl 4 , Bi(NO 3 ) 3, and dopamine to react at 60 °C.…”

“…In addition, peroxidase activity can also catalyze the production of ROS, thus combining SAzyme with photodynamic therapy is a promising method for highly curative treatment of tumors. [98] Li Qiu's group [31] synthesized a polymeric spherical nanozyme by self-assembly reaction using 5,10,15,20-tetrakis(4-pyridyl) porphyrin and pyridine nitrogen-containing substances as ligands and Pd atoms as linking sites. The POD-like enzymatic activity of this SAzyme can be significantly enhanced by ultrasound and light irradiation, resulting in favorable acoustodynamic and photodynamic therapeutic effects.…”

Emerging Single‐Atom Catalysts/Nanozymes for Catalytic Biomedical Applications

“…In 2021, Du et al fabricated a porphyrinbased polymeric network coordinated with Pd single atoms (Pd-Pta/Por) for sono-/photo-/chemo-trimodal tumor therapies. [102] The Pd-Pta/Por was prepared from PdCl 4 2− , 5,10,15,20-tetra(4pyridyl)-21H,23H-porphine (Por) which acted as a linker due to its sono-/photosensitizer characteristic, and tri(pyridin-4-yl) amine (Pta) in the presence of PVP and dilute HCl via a coordination-driven self-assembly approach (Figure 7a). The resulting Pd-Pta/Por possessed POD-like catalytic activity and could generate abundant •OH from H 2 O 2 for CDT.…”

A Library of ROS‐Catalytic Metalloenzyme Mimics with Atomic Metal Centers

“…The versatility of transition metal electronic states and coordination modes lays the foundation for transition metal catalysis in chemistry, which also provides opportunities to develop new AMEs starting from nature's vast collection of metalloproteins. [5][6][7][8] Since the ferromagnetic nanoparticles were reported with peroxidase (POD)mimetic activity, [9] a lot of metalnanomaterialbased AMEs, exhibiting biocatalytic activities of oxidase (OXD), [10,11] POD, [12] halogen peroxidase (HPO), [13] etc., have been discovered, [8,[14][15][16] among which, the metalNcoordinated centers supported by carbo naceous substrates have emerged as promising candidates to engineer AMEs to mimic the biocatalytic effects of their natural counterparts. [16][17][18][19][20][21] However, their catalytic activities, substrates' selectivities, kinetics, and reactive oxygen species (ROS) products have not been investigated since the synthesis of AMEs that consist of different atomic metalN centers but exhibit similar physicochemical and coordination structures remains a substantial challenge.…”