Multivalent ApoAI Peptide Display on Nanoparticles for Cholesterol Efflux

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Solution Overview

Problem

Current treatments for atherosclerosis and related cardiovascular diseases are inadequate in effectively addressing the accumulation of cholesterol in arterial intima, leading to thrombosis and plaque rupture, which can result in myocardial infarction or stroke, with long-term consequences for patients.

Innovation Solution

Development of multivalent nanoparticle-peptide conjugates, specifically using biomimetic ApoAI peptides chemically conjugated to the surface of nanoparticles, such as virus-like particles or rod-shaped virus nanoparticles, to enhance cholesterol efflux and reduce reactive oxygen species, thereby ameliorating atherosclerosis and cardiovascular disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for atherosclerosis are used, then the disease can be managed to some extent, but they are inadequate in effectively addressing cholesterol accumulation in arterial intima

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidability to address cholesterol accumulation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses nanoparticles as intermediary carriers to deliver ApoAI peptides to the target site (arterial intima). The nanoparticles serve as a mediator between the therapeutic agent (ApoAI) and the disease site, enabling effective cholesterol efflux from macrophages in the arterial wall. This intermediary approach overcomes the limitations of current treatments that cannot effectively address cholesterol accumulation.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the therapeutic delivery system by using nanoparticles with specific size ranges (20-200 nm) and surface properties. The multivalent display of ApoAI peptides on nanoparticle surfaces creates high local concentrations, and the PEGylation modifies the hydrodynamic radius and circulation time. These parameter changes enable the treatment to effectively penetrate and act on cholesterol-laden macrophages in arterial intima.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If multivalent nanoparticle-peptide conjugates are developed, then cholesterol efflux is enhanced and atherosclerosis is ameliorated, but the device complexity increases

Engineering Contradiction:

Improvecholesterol efflux enhancementVSAvoidnanoparticle conjugate structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the therapeutic system into distinct functional modules: (1) nanoparticle core for structural stability and multivalent display, (2) PEG linker for stability and circulation, and (3) ApoAI peptide for cholesterol efflux function. This segmentation allows each component to be optimized independently while maintaining overall effectiveness, managing the complexity through modular design.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The nanoparticle platform is designed to be universal and multi-functional: it can display multiple copies of ApoAI peptides (multivalent), provides steric stabilization through PEGylation, enables targeted delivery to arterial macrophages, and can potentially carry other therapeutic agents. This multi-functionality consolidates multiple requirements into a single platform, managing complexity through consolidation rather than separate systems.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The nanoparticle-peptide conjugates increase cholesterol efflux and endothelial cell healing, reducing oxidative stress and improving the atherosclerosis disease state, providing a safe and effective treatment for cardiovascular diseases.

Implementation Method 1

enhance cholesterol efflux and reduce reactive oxygen species

Methodology Applied

Scientific EffectCholesterol efflux:

Implementation Method 2

reducing oxidative stress and improving the atherosclerosis disease state

Methodology Applied

Scientific EffectOxidative stress reduction: Oxidation

Data Source

PatentUS20250332278A1Multivalent display of apoai peptide on nanoparticles against atherosclerosis

Publication Date: 2025.10.30 RGT UNIV OF CALIFORNIA

AI summary

Methods and compositions for the treatment of atherosclerosis or cardiovascular disease are provided herein. The compositions and methods contain a nanoparticle-peptide conjugate that reduces LDL concentration in a subject, reduces reactive oxygen species in the subject, or increases cellular healing rate.