Construction of an enzyme-responsive cascade nanoreactor and its application in disease diagnosis and treatment
Enzyme-responsive cascade nanoreactors are intelligent biomaterials that use enzymes as endogenous stimuli to achieve changes in the structure, properties, and function of nanomaterials and can be used in the diagnosis and treatment of diseases. Enzyme-based nanocomposite hydrogel for sensitizing osteosarcoma: bioactive nanoparticles (MDA-NPs) composed of magnesium oxide nanoparticles (M-NPs) and polydopamine (2-AM) with phosphonate-modified methacrylamide chitosan (CMP) and polyacrylamide (PAM) into a series of MDA-NPs nanocomposite materials. This hydrogel shows equilibrium photothermal effects, mechanical properties, and osteogenesis, and MDA-NPs can be used as co-crosslinkers, photothermal agents, and Mg2 + reservoirs. The hydrogel and near-infrared (NIR) laser irradiation can effectively inhibit human osteosarcoma cells (143B), achieving complete inhibition of tumor recurrence in vitro and in vivo. The released Mg2 + effectively promoted the osteogenic activity of mouse embryonic osteoblast precursor cells (MC3T3-E1), and the hydrogel showed highly efficient bone repair performance in a rat model of severe cranial defect 1. Enzyme-based nanocomposite hydrogels for enhanced tumor photodynamic therapy: enzyme-based nanocomposite hydrogels can be used to enhance tumor photodynamic therapy. The hydrogel is crosslinked by polyethylene glycol dimethacrylate (PEGDMA) and contains two different types of nanoparticles: polylactic acid-polyethylene glycol copolymer (PLA-PEG) nanoparticles containing the photosensitizer iron porphyrin (FePc) and hydrogen peroxide decomposition catalyst iron oxide (Fe3O4), and polyethylene glycol-polypropylene copolymer (PEG-PCL) nanoparticles containing hydrogen peroxide generation catalyst copper oxide (CuO) and glucose oxidase (GOx). When this hydrogel is injected into the tumor site, GOx can catalyse the formation of hydrogen peroxide from glucose due to the high concentration of glucose and low pH in the tumor microenvironment, while CuO can further decompose the hydrogen peroxide to release oxygen. At the same time, due to the presence of highly active enzymes in the tumor microenvironment, such as phosphoestase (PPase) and protease (Protease), they can degrade the crosslinking point of the hydrogel and the shell of the nanoparticles, promoting the release of FePc and Fe3O4. When the hydrogel is exposed to NIR light, FePc can produce singlet oxygen, while Fe3O4 can decompose hydrogen peroxide and further increase the oxygen supply. In this way, the hydrogel can achieve highly efficient photodynamic therapy of the tumors, while avoiding the systemic toxicity of the photosensitizer and the effects of the hypoxic environment. Enzyme-based nanocomposite hydrogels for tumor diagnosis and treatment: Enzyme-based nanocomposite hydrogels can be used for tumor diagnosis and treatment. The hydrogel is cross-linked with polyethylene glycol dimethacrylate (PEGDMA) and contains two different types of nanoparticles: a PLA-polyethylene glycol copolymer containing a fluorescent probe and the chemotherapy drug doxorubicin (DOX)
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