Modified Apolipoprotein Nanoparticles for Macrophage Targeted Imaging
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Solution Overview
Problem
Current imaging techniques for cancer and atherosclerosis, such as MRI, face challenges in achieving targeted and specific delivery of contrast agents to tumor-associated macrophages and atherosclerotic plaques, leading to low efficacy and potential systemic toxicity due to non-specific distribution of gadolinium-based contrast agents.
Innovation Solution
Development of nanoparticles comprising chemically or enzymatically modified apolipoproteins, specifically apolipoproteins A-I and A-II, combined with metallic or non-metallic contrast agents, which are designed to target macrophages through scavenger receptors, allowing for enhanced accumulation and reduced systemic dosage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If gadolinium-based contrast agents are administered systemically for imaging, then imaging coverage is improved, but specificity to target cells deteriorates
Solution Approach 1:
The patent uses modified apolipoproteins as intermediary carriers that selectively bind to scavenger receptors on macrophages. These apolipoprotein-based carriers transport gadolinium contrast agents specifically to target cells, acting as mediators between the systemic circulation and the target macrophages, thereby achieving both high imaging efficacy and cell-specific targeting.
2Measurement precision
If high dosage of contrast agents is used to improve imaging signal, then imaging quality is improved, but systemic toxicity increases
Solution Approach 1:
The patent implements local quality by concentrating the contrast agent specifically at the target site (macrophages) through selective binding of modified apolipoproteins to scavenger receptors. This localized delivery ensures high imaging quality at the target while minimizing the contrast agent concentration in non-target tissues, thereby reducing systemic toxicity.
3Stability of the object's composition
If non-modified apolipoproteins are used for nanoparticle formation, then nanoparticle stability is improved, but macrophage targeting capability deteriorates
Solution Approach 1:
The patent applies parameter changes by chemically modifying apolipoproteins (such as oxidation of methionine residues) to alter their properties. These modifications enable the apolipoproteins to be recognized by scavenger receptors on macrophages while maintaining nanoparticle stability, thus achieving both stable nanoparticle formation and effective macrophage targeting.
Data Source
AI summary
A new approach to targeting imaging agents to macrophage-rich sites of interest is disclosed. Compositions of the invention are rHDL and HDL-like liposomal compositions, protein constituents of which, apolipoproteins A-I and/or A-II or fragments thereof are used not only as structural but also as targeting agents. This is achieved by certain controlled chemical or enzymatic modification of apolipoproteins A-I or A-II or fragments thereof. Such modification converts these apolipoproteins to substrates for macrophage scavenger receptors and results in the improvement of contrast agent-(HDL/modified apolipoprotein)-particle association with macrophages and/or absorption (uptake) by macrophages when compared to that of the contrast agent-(HDL/apolipoprotein)-particle constructed with non-modified naturally occurring apo A-I. The compositions can be used for noninvasive specific in vivo molecular detection and localization of macrophage-rich sites of interest using imaging techniques such as computed tomography (CT), gamma-scintigraphy, positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI).