Background of Drug Discovery Targeting Lysosomal Membrane Permeability and Integrity
Lysosomes are membrane-encapsulated organelles that mediate the intracellular degradation of macromolecules and play a key role in cell death in physiological and pathological settings. Therefore, maintaining the integrity and function of lysosomes is essential for cellular homeostasis. Under different forms of stress conditions, lysosomal membrane permeabilisation (LMP) or complete rupture of lysosomes occurs and leakage of lysosomal contents into the cytoplasm triggers inflammatory responses and cell death. Thus, defective membrane permeability and integrity may not only lead to inflammatory diseases, lysosomal storage disease (LSD), neurodegenerative diseases, but may also be a tool that researchers can use to treat cancer. Recent renewed interest in the therapeutic potential of lysosomal rupture against cancer has led to the development of lysosomal disrupting agents that induce lysosomal membrane permeabilisation, cathepsins release and subsequent lysosome-dependent cell death (LDCD).
Fig. 1. Mechanisms of LMP induction. (Berg A L, et al., 2022)
Solutions
Lysosomal membranes are normally protected by highly glycosylated membrane proteins, and oncogene-mediated down-regulation of these glycoproteins makes lysosomes more sensitive to LMP. Therefore, depletion of cancer cells by LMP is an attractive therapeutic strategy, especially against apoptosis-resistant cancer cell populations. Our scientists use lysosomal membranes as highly relevant targets for therapeutic interventions in cancer to develop appropriate targeting measures. Our goal is to help you design custom drugs that destabilize lysosomal membranes to kill cancer cells from within.
Based on an understanding of the unique characteristics of cancer-associated lysosomal expression (i.e. size, hydrolase content, and membrane fragility), CD BioSciences is committed to providing our global customers with strategies to target lysosomal membrane permeability and integrity in cancer.
Targeting Delivery of Nanoparticles
Nanoparticles can accumulate in the lysosome and induce cell death on their own. We modify the surface of nanoparticles (e.g. silica nanoparticles, metal nanoparticles, and amine-modified nanoparticles) to target cancer cells, generate ROS in specific tissue regions and disrupt the targeted lysosomes.
Targeting Sphingolipids
Cancer cells cause specific changes in the composition of membrane lipids and major lysosomal proteins compared to normal cells. We design compounds that target lysosomal membrane sphingolipids to disrupt the precise balance of sphingolipid species and achieve destabilisation of the lysosomal membrane.
Targeting Reactive Oxygen Species
Increased ROS production stimulates lipid peroxidation and lysosomal membrane destabilisation. Iron-containing macromolecules are degraded in the lumen of the lysosome in the presence of reducing agents. We design iron-containing proteins or iron complexes to target lysosomes associated with cancer, leading to ROS-mediated LMP and cell death.
Targeting the Microtubule Cytoskeleton
We design microtubule modulators, including paclitaxel, vincristine, Deox b7,4 and BpV (phen) to induce LMP and apoptosis.
Targeting Autophagy-Related Proteins
The possible crosstalk between autophagy and LMP provides additional options for targeting LMP. We design effective autophagy inducers to target autophagy proteins to achieve lysosome enlargement and lysosomal membrane damage.
Why Choose Us
- Cutting-edge tools are used to assess the extent of LMPs and specific signals released by lysosomes on LMP.
- Targeting multiple key molecules interferes with the stability and integrity of lysosomal membranes.
- Rapid experimental process to deliver results at an economical cost.
- Collaborate with experienced international technical staff.
CD BioSciences can meet any reasonable needs of our clients, taking time and budget into consideration for you. Our aim is to be customer-centric and to provide the highest quality services to customers. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, 7 days a week. If you are interested in our services, please feel free to contact us for more information or a detailed discussion.
Reference
- Berg A L, et al. (2022) Engaging the Lysosome and Lysosome-Dependent Cell Death in Cancer[J]. Exon Publications. 195-230.