Phosphatidylserine in the medical field

Phosphatidylserine (PS), a phospholipid compound in cell membranes, is expanding its applications in the medical field from traditional adjuvant therapy to innovative drug carriers. The specific applications are analyzed in two major dimensions:

I. Clinical Value as an Adjuvant Therapeutic Ingredient

1. Functional Improvement in Neurological Diseases

Cognitive Support for Alzheimer's Disease (AD): PS improves synaptic function by regulating membrane fluidity and neuronal signaling. Clinical studies show PS supplementation delays memory decline in mild cognitive impairment patients, possibly by promoting acetylcholine synthesis and reducing β-amyloid deposition.

Mood Regulation for Depression and Anxiety: PS enhances the sensitivity of 5-hydroxytryptamine and dopamine receptors. Some research indicates that combining PS with antidepressants improves treatment efficacy, especially for depressed patients with cognitive decline.

Intervention for Childhood Developmental Disorders: For autism and attention deficit hyperactivity disorder (ADHD), PS stabilizes neuronal membranes to improve neurotransmitter transmission, assisting in relieving attention distraction and social impairment symptoms.

2. Auxiliary Management of Cardiovascular and Metabolic Diseases

Regulating Lipids and Vascular Health: PS promotes high-density lipoprotein (HDL) synthesis while inhibiting low-density lipoprotein (LDL) oxidation, reducing the risk of atherosclerosis. Animal experiments show it decreases vascular endothelial inflammatory factor release.

Protection Against Diabetic Neuropathy: By improving energy metabolism and antioxidant capacity in nerve cells, PS delays the progression of peripheral neuropathy in diabetic patients and alleviates symptoms like limb numbness.

3. Intervention in Immune System and Aging-Related Diseases

Enhancing Immune Cell Activity: As a membrane component of antigen-presenting cells (e.g., dendritic cells), PS regulates T-cell activation efficiency, assisting in improving the response rate of immune checkpoint inhibitors in tumor immunotherapy.

Delaying Aging Processes: By reducing oxidative stress damage to cell membranes, PS maintains normal cellular functions. It is often combined with coenzyme Q10 and other ingredients in anti-aging health products to improve physical and cognitive vitality in the elderly.

II. Innovative Application Potential as a Drug Carrier

1. Construction of Targeted Delivery Systems

Brain-Targeted Drug Carriers: Leveraging PS's affinity for neurons, drug delivery systems (e.g., PS-liposomes) are prepared by combining PS with liposomes, enabling blood-brain barrier penetration for brain targeting. For example, in Parkinson's disease treatment, PS carriers encapsulating dopamine precursor drugs increase brain drug concentration and reduce peripheral side effects.

Active Tumor Targeting: Phosphatidylserine receptors on tumor cells (e.g., TIM-4, Baiap2l1) recognize PS. PS-modified nanoparticles (e.g., PS-PEG-nanoliposomes) are designed to carry chemotherapeutic drugs (e.g., paclitaxel), specifically accumulating in tumor tissues to enhance efficacy and reduce systemic toxicity.

2. Gene Therapy and Vaccine Delivery

siRNA Delivery Carriers: After complexing PS with cationic lipids, siRNA can be encapsulated into nanocomplexes, entering cells via endocytosis to efficiently silence disease-causing genes (e.g., cancer-related genes). Its advantage lies in high biocompatibility, reducing nuclease degradation of siRNA.

Vaccine Adjuvants and Delivery Platforms: PS enhances antigen-presenting cell uptake and processing of vaccine antigens. For example, in mRNA vaccines, PS-modified lipid nanoparticles (LNPs) improve intracellular mRNA delivery efficiency while activating innate immune responses to enhance antibody production.

3. Auxiliary Tools for Cell Therapy and Regenerative Medicine

Stem Cell Membrane-Encapsulated Carriers: Integrating PS into stem cell exosomes or membrane vesicles enhances their homing ability to damaged tissues. For instance, in myocardial infarction treatment, PS-modified mesenchymal stem cell exosomes more precisely target damaged myocardial cells, releasing growth factors to promote repair.

III. Key Challenges and Optimization Directions in Applications

Stability and Scale Production: PS is susceptible to oxidation and enzymatic hydrolysis, requiring chemical modification (e.g., fatty acid chain saturation) or lyophilization to improve stability. Its natural sources (e.g., bovine brain, soybean) limit production, necessitating the development of microbial fermentation or enzymatic synthesis technologies.

Enhancing Targeting Efficiency: Although PS has natural targeting properties, its binding affinity to receptors needs optimization through molecular design (e.g., coupling targeting peptides) or combining responsive materials (e.g., pH-sensitive polymers) for environment-triggered release.

With the development of nanobiotechnology, phosphatidylserine is evolving from a single-function adjuvant therapeutic ingredient to a multifunctional molecule integrating biological activity and carrier functions, warranting continuous attention to its application prospects in precision medicine.