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Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA–MnO2-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA–MnO2-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO2, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA–MnO2-IR780 was delivered to the tumor site, MnO2 was decomposed by hydrogen peroxide, producing Mn2+ and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA–MnO2-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA–MnO2-IR780 for safe and highly-efficiency synergistic therapy for cancer.

The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn

A N-carbamoyl-D-amino acid amidohydrolase gene (hyuC) from Sinorhizobium morelens S-5 was cloned by LA PCR, and its nucleotide sequence was determined. The deduced amino acid sequence encoded by the hyuC gene exhibited high homology to the amino acid sequences of D-carbamoylase from other sources. The gene could be highly expressed in Escherichia coli, and the recombinant enzyme was purified 16.1-fold to homogeneity with a yield of 21.2% by heat treatment and three steps of column chromatography. The results of gel filtration on Superdex 200 HR and SDS-polyacrylamide gel electrophoresis suggested that the enzyme was a tetramer protein of identical 38-kDa subunits. The recombinant enzyme catalyzed the hydrolysis of N-carbamoyl alpha-amino acid to the corresponding free amino acid, and it was strictly D-specific. The enzyme showed broad substrate specificity, and exhibited high activity in the hydrolysis of N-carbamoyl-D-p-hydroxyphenylglycine as substrate. The enzyme did not hydrolyze N-carbamoyl-beta-alanine. The optimum pH and temperature of the enzyme were pH 7.0 and 60 degrees C, respectively. Enzyme activity was slightly improved by Ca2+ and Fe2+, and nearly not affected by metal chelators and sulfhydryl reagents. The enzyme showed high thermal and oxidative stability. These results show that the enzyme has great potential for industrial application.