Tumor protein 53 (TP53) mutation in bladder carcinoma (BC), upregulates the transcription of carbamoyl phosphate synthetase 1 (CPS1), to reduce intracellular ammonia toxicity. To leverage ammonia combating BC, here, an intravesically perfusable nanoporter-encased hydrogel system is reported. A biomimetic fusogenic liposomalized nanoporter (FLNP) that is decorated with urea transporter-B (UT-B) is first synthesized with protonated chitosan oligosaccharide for bladder tumor-targeted co-delivery of urease and small interfering RNA targeting CPS1 (siCPS1). Mussel-inspired hydrogel featured with dual functions of bio-adhesion and injectability is then fabricated as the reservoir for intravesical immobilization of FLNP. It is found that FLNP-mediated UT-B immobilization dramatically induces urea transportation into tumor cells, and co-delivery of urease and siCPS1 significantly boosts ammonia accumulation in tumor inducing cell apoptosis. Treatment with hybrid system exhibits superior anti-tumor effect in orthotopic bladder tumor mouse model and patient-derived xenograft model, respectively. Combined with high-protein diet, the production of urinary urea increases, leading to an augmented intracellular deposition of ammonia in BC cells, and ultimately an enhanced tumor inhibition. Together, the work establishes that cascade modulation of ammonia in tumor cells could induce tumor apoptosis and may be a practical strategy for eradication of TP53-mutated bladder cancer.
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http://dx.doi.org/10.1002/advs.202206893 | DOI Listing |
Prep Biochem Biotechnol
January 2025
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
L-asparaginase (asparagine amidohydrolase) contributes to 40% of the total enzyme demands worldwide and is one-third of the global requirement as an anti-cancerous drug in treating acute lymphocytic leukemia (ALL), a type of leukemia. This protein breaks down L-asparagine into aspartic acid and ammonia those involved in ALL, rely on for growth and survival. Both non-recombinant and recombinant L-asparaginase can be produced by bacteria when a suitable substrate and method (solid-state fermentation (SSF) or submerged fermentation (SmF) which are techniques to grow microorganisms under controlled conditions), is provided.
View Article and Find Full Text PDFNature
January 2025
SUGAR, X-star, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Japan.
Foraminifera are ubiquitous marine protists that intracellularly accumulate phosphate, an important macronutrient in marine ecosystems and in fertilizer potentially leaked into the ocean. Intracellular phosphate concentrations can be 100-1,000 times higher than in the surrounding water. Here we show that phosphate storage in foraminifera is widespread, from tidal flats to the deep sea.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City 32897, Egypt.
Cancer cells undergo metabolic rewiring to support rapid proliferation and survival in challenging environments. Glutamine is a preferred resource for cancer metabolism, as it provides both carbon and nitrogen for cellular biogenesis. Recent studies suggest the potential anticancer activity of amino acid analogs.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China; Key Laboratory of Veterinary Biotechnology of Henan Province, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, China. Electronic address:
Ammonia can cause cells to produce a large amount of reactive oxygen species (ROS), leading to the oxidative stress of cells. As the main intracellular reductant, nicotinamide adenine dinucleotide phosphate (NADPH) plays a crucial role in maintaining reduced glutathione (GSH), helping to remove ROS and protect cells from oxidative damage. Our study demonstrated that SIRT5 desuccinylated isocitrate dehydrogenase 2 (IDH2) to enhance its activity, resulting in increased NADPH production.
View Article and Find Full Text PDFNanoscale
December 2024
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Ammonia (NH) is an important commodity chemical used as an agricultural fertilizer and hydrogen-storage material. There has recently been much interest in developing an environmentally benign process for NH synthesis. Here, we report enhanced production of ammonia from diazotrophs under light irradiation using hybrid composites of inorganic nanoparticles (NPs) and bacterial cells.
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