The Silent Threat: Chronic liver disease accounts for approximately 2 million fatalities annually worldwide. (11th leading cause of death in the whole world)

It leads to individuals having advanced liver diseases and even hepatic failure. However, their nature often eludes early diagnosis, as they cloak themselves in asymptomatic guise during their nascent stages. Normal physical examinations and nonspecific biological abnormalities for the detection of these diseases remain hard to find until they have stealthily advanced, often leading to poor medium-term prognosis. Therefore, our team hopes to relieve this deplorable situation. We hope to predicate on the injury of hepatocytes, developing into the inflammatory stage.

• Hepatocytes have a pivotal role in liver’s physiological functioning. Upon sustaining injury, these cells release cytokines that trigger multifaceted signaling cascades involving Kupffer cells and myofibroblasts.
• Kupffer cells, specialized resident macrophages in the liver, contribute to immune response in the liver, while myofibroblasts, assemblages of cells, secrete extracellular matrix (ECM) proteins, help in wound healing and fibrogenesis.
• Hepatic stellate cells (HSCs), receive signals and transit from a quiescent state to an activated state. These activated HSCs (aHSCs) mimic the behavior of myofibroblasts, excreting alpha-smooth muscle actin (α-SMA) and collagen to orchestrate the development of ECM, the principal constituent of fibrosis. ECM then undergoes degradation following liver injury recovery, preventing long-term fibrogenesis.

We hope to deliver a liposome-coated drug through RBC transportation, wherein a fusion protein comprising GATA4 is expressed.

• GATA4
  → A transcription factor, involved in cellular proliferation and differentiation

For GATA4 internalization into cells, we employ liposomes that facilitate endocytosis to enhance their uptake by aHSCs.

By ligand attachment through PEGylation, involving the binding of polyethylene glycol (PEG) to molecules and macrostructures such as liposomes, augmenting their favorable characteristics.

During liver fibrosis, aHSCs predominantly express various receptors on their cellular membrane, including PDGFRβ (Platelet-derived growth factor receptor beta), RBP R (Retinol binding protein receptor), and CD44. These receptors will be attracted by the ligated liposome drug membrane, facilitating efficient drug delivery.

By targeting the cause of fibrosis at cellular level, we aspire to offer a more effective therapeutic intervention for these conditions.

Our approach boasts several promising facets. Firstly, it harnesses the innate processes of the human body by utilizing liposomes that aid endocytosis to facilitate the entry of GATA4 into activated Hepatic Stellate Cells (aHSCs). This approach mitigates side effects and elicits a more favorable response in patients. Secondly, our solution exhibits a high level of specificity, precisely targeting on aHSCs. During liver fibrosis, aHSCs predominantly express an array of receptors on their cellular membrane, including PDGFRβ, RBP R, and CD44. These receptors will be enticed by the ligated liposome drug membrane, facilitating targeted drug delivery.

1. clinical trials to ascertain the safety and efficacy of our solution.
2. large-scale manufacturing looms. Producing liposome-coated drugs in quantities.
3. ensuring accessibility: guarantee broad patient access

While our solution offers a promising new approach to addressing chronic liver diseases, much groundwork can still be done, but our solution has the potential to save the lives of patients grappling with these conditions.

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