Endogenous Nitric Oxide Releases In Situ for RNS/ROS Synergistic Cancer Therapy

Abstract

Gas therapy, represented by nitric oxide (NO), has shown a powerful anti‐tumor effect. However, current NO therapy relies on NO precursors, which are often released prematurely during in vivo delivery, resulting in poor targeting and obvious toxic side effects. Herein, a core/shell‐structured nanocatalyst is designed and prepared to catalyze the generation of NO in tumor without introduction of NO donor. In this system, C‐Z@CM is prepared by coating the octahedron of Cu‐MOF with a nano‐ZnO, and camouflaging homologous tumor cell membrane. After the nanomedicine is taken up by tumor cells, ZnO reacts in situ with endogenous S‐nitrosoglutathione (GSNO), which is highly expressed in tumors, to continuously and stably generate NO. In addition, the dispersed copper ions in C‐Z@CM acts as the catalytic active centers of the Fenton‐like reaction, which catalyzes H2O2 to generate a large number of hydroxyl radicals (•OH). Importantly, the cascade of NO and reactive oxygen species (ROS) leads to the massive production of more lethal reactive nitrogen species (RNS), further enhancing the therapeutic effect. Catalytic production of high concentrations of NO in situ in the tumor, combined with the cascade generation of ROS and RNS, accompanied by glutathione (GSH) depletion, achieving effective tumor suppression.

Cell Membrane-Coated Biomimetic Nanoparticles in Cancer Treatment

“…PLTm@NPs Breast cancer [40][41][42] Colon cancer [42,43] Liver cancer [44] Nm@NPs Breast cancer [7,28] Liver cancer [45] Pancreatic cancer [46,47] Mm@NPs Breast cancer [48][49][50] Osteosarcoma [51] Glioma [52] Tm@NPs Melanoma [53,54] Liver cancer [55] Glioma [56] Lymphoma [57] DCm@NPs Melanoma [58,59] Breast cancer [60,61] Liver cancer [62] Glioma [63] NKm@NPs Breast cancer [64] Liver cancer [65] Glioma [66,67] SCm@NPs Liver cancer [68] Bone cancer [69] Prostate cancer [70] CCm@NPs Melanoma [71][72][73] Cervical cancer [74,75] Breast cancer [76,77] Colon cancer [78] Osteosarcoma [79,80] Colorectal cancer [81] Oral squamous cell carcinoma [82] Bladder cancer [83]...…”

“…A powerful anti-tumor effect has been demonstrated with nitric oxide (NO) gas therapy. In Xu and colleagues’ research [ 74 ], as depicted in Figure 13 , a copper-based metal–organic framework (MOF) material was synthesized. This material triggers the generation of hydroxyl radicals (•OH), with ZnO doping enhancing NO production from endogenous S-nitrosoglutathione (GSNO) at tumor sites.…”

Advances in Nanodynamic Therapy for Cancer Treatment

“…Furthermore, endogenous gasotransmitters, such as nitric oxide (NO) and carbon monoxide (CO), act in concert with SDT to fight tumors effectively when elevated [89]. This synergy occurs through various mechanisms, including mitochondrial and DNA damage, DNA repair inhibition, cellular respiration suppression, and inflammation amplification [90]. Gas-assisted therapy, when combined with SDT, has been proposed to augment the therapeutic impact.…”

Coordination catalysis of metals and polydopamine enables controlled release of CO from MnCO by enhancing oxidative stress and the thermal effect

“…3,4 Therapeutic gases, e.g., nitric oxide (NO), hydrogen sulfide (H 2 S) and carbon monoxide (CO), can reverse the Warburg effect and thus have remarkable anticancer potency at appropriate levels. [5][6][7][8][9][10] These gases exhibit similar anticancer functions and mechanisms, while CO is much safer due to its higher blood poisoning concentration than NO and H 2 S. 11 However, due to the strong affinity for hemoglobin, the use of CO is highly risky. Therefore, efficient delivery and precise release at the tumor site are extremely important for CO therapy.…”