Lysosomes (Tritosomes):A predictive in vitro test system for catabolism or lysosomal stability studies

IPHASE Products

Introduction to Lysosomes
The lysosome was discovered by Christian deDuve in the 1950s and established as the central organelle of degradation and metabolism in the cell. Lysosomes are single-membrane, dynamic, heterogeneous organelles that vary in location, morphology, size, enzyme content, and substrates. The lysosomal membrane contains hundreds of peripheral membrane proteins, including a variety of transporters and ion channels. The lysosomal multi-subunit V-ATPase maintains the acidic lysosomal lumen. This low pH (4.5-5.5) activates >50 lysosomal hydrolases that digest macromolecules including proteins, nucleic acids, lipids, and carbohydrates. Lysosomes receive and digest small molecules and endocytosed materials, engulf large particles such as apoptotic cell corpses and pathogenic bacteria, or autophagocytose cytoplasmic contents, including damaged mitochondria, endoplasmic reticulum, and lysosomes. Therefore, lysosomes have long been considered the "recycling bin" of the cell.

Tritosome

Tritosomes are specialized subcellular structures involved in various cellular processes, particularly in the regulation of metabolic pathways and the maintenance of cellular homeostasis. Tritosomes are often studied in the context of their role within specific organism models. The defining aspect of these structures is their unique composition, which allows them to perform intricate functions that are critical for the survival and proper functioning of cells. Rat liver tritosomes are hepatic lysosomes that have been loaded with Tyloxapol (Triton WR 1339), a non-ionic surfactant. Lysosomes containing tylosapol exhibit reduced density, can be more efficiently isolated from mitochondria, and contaminate organelles that overlap with natural lysosomal densities.

Application of lysosomes
· Small nucleic acid drugs and lysosomes
Small nucleic acid drugs refer to small fragments of nucleotides with specific sequences that can bind to specific mRNAs and interfere with the translation efficiency of mRNAs to ultimately achieve therapeutic effects. Small nucleic acid drugs include antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA (miRNA), RNA aptamers, etc. Among them, ASO and siRNA are the current mainstream research directions of small nucleic acid drugs.

After administration, small nucleic acid drugs first need to avoid degradation by nucleases in plasma and tissues, capture by the immune system, successfully reach the target tissue, enter the cell through endocytosis, and escape before the endosome combines with the lysosome, enter the cytoplasm, and combine with the target mRNA to achieve gene silencing, thereby exerting drug efficacy. Lysosomes can be used as an efficient test system to evaluate the changes in the stability of modified small nucleic acid drugs after the action of lysosomes in vitro, providing data support for the research of small nucleic acids.

· Antibody-drug conjugate (ADC) and lysosomes
Antibody-drug conjugate (ADC) is a new type of biotechnology drug that couples small molecule compounds to targeted antibodies or antibody fragments through linkers. It can enhance drug targeting and stability, reduce clinical toxicity and side effects, and improve the therapeutic index. It has both the killing effect of traditional small molecule drugs and the targeting of antibody drugs. It is mainly used in targeted treatment of anti-tumor or other diseases.

After entering the body, the ADC molecules can bind to the antigens on the surface of the target cells through the guidance of the monoclonal antibodies, and further transfer into the target cells. The ADC molecules that enter the cells (mainly in the lysosomes) can release small molecule toxins and/or toxin analogs (i.e., effector molecules) through chemical and/or enzymatic action to "kill" the target cells. ADC requires functional lysosomes to decompose and release small molecule drugs that exert their efficacy, penetrate through the lysosomal membrane or transport out of the lysosomes, and interact with molecular targets in the cytoplasm or nucleus. In vitro experiments of ADC and lysosomes can evaluate whether the linker can be effectively cut by the lysosomes to release the small molecule drugs it carries, providing an in vitro evaluation tool for the design of ADC linkers.

About IPHASE
As a leading supplier of in vitro biological reagents for drug development, IPHASE has launched liver lysosome products of five species, including human, monkey, dog, rat and mouse, through continuous optimization and testing, relying on its professional R&D and production team to help drug development.
· High enzyme activity: IPHASE liver lysosomes have been tested for cathepsin B and acid phosphatase activity, and the enzyme activity is comparable to or higher than similar imported products.
· Batch production: Batch production is adopted, and the inventory is sufficient to ensure the supply of the same batch of products.
· Short delivery time: Independent research and development, multiple warehouses in stock, to ensure customer use needs.