Ultrasound-Sensitive Peptide Nanoparticles for Cytoplasmic Delivery

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Solution Overview

Problem

Existing protein and nucleic-acid based therapeutic agents face challenges with ineffective distribution to diseased tissues, poor stability in physiologic environments, and toxic side effects, while traditional biocarriers rely on endocytic transport leading to degradation, and there is a need for advanced imaging techniques to monitor immune cells like macrophages for therapeutic interventions.

Innovation Solution

Development of ultrasound-sensitive peptide nanoparticles with a perfluorocarbon liquid core and amphiphilic peptides that allow direct intracellular delivery of therapeutic agents and enable non-invasive, real-time imaging of macrophages by phase transition upon ultrasound application.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional biocarriers are used for protein and nucleic-acid delivery, then therapeutic agents can be delivered to target cells, but the agents undergo endosomal degradation leading to loss of biological activity

Engineering Contradiction:

Improvebiological activity retentionVSAvoidendocytic transport pathway

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs phase transitions of perfluorocarbon liquid core in response to ultrasound stimulation to trigger direct membrane disruption and cytoplasmic delivery, bypassing the endocytic pathway and avoiding endosomal degradation of therapeutic agents

Inventive Principle:

Principle #36Phase transitions

Solution Approach 2:

The invention replaces the biological endocytic transport mechanism with an acoustic field-driven mechanical disruption mechanism, where ultrasound-induced phase transition directly disrupts the membrane to deliver cargo into the cytoplasm

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If protein and nucleic-acid based therapeutic agents are administered, then potent therapeutic effects are achieved, but ineffective distribution to diseased tissues and poor stability in physiologic environments occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidstability in physiologic environment

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent creates composite peptide nanoparticles combining perfluorocarbon liquid core with amphiphilic peptide shells, where the composite structure provides both stability in physiologic environments and targeted delivery capability to diseased tissues

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The invention utilizes parameter changes in the perfluorocarbon liquid core, specifically its phase transition properties in response to ultrasound frequency and intensity, to control delivery timing and location, thereby improving both stability and therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If advanced imaging techniques are developed to monitor macrophages, then detailed spatial resolution and prolonged monitoring capabilities are achieved, but invasive procedures and complex methodology are required

Engineering Contradiction:

Improvespatial resolution for macrophage imagingVSAvoidimaging system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The peptide nanoparticles serve multiple functions: they deliver therapeutic cargo into the cytoplasm and simultaneously act as ultrasound-responsive imaging agents, enabling both therapy and non-invasive monitoring of macrophages with a single system

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The ultrasound-induced phase transition of the perfluorocarbon liquid core provides both the mechanical force for cytoplasmic delivery and the acoustic contrast for non-invasive imaging, simplifying the overall system while achieving both therapeutic and diagnostic goals

Inventive Principle:

Principle #36Phase transitions

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 nanoparticles facilitate direct cytoplasmic delivery of therapeutic agents without endosomal degradation and provide detailed spatial resolution for macrophage imaging, enhancing therapeutic efficacy and monitoring capabilities.

Implementation Method 1

phase transition upon ultrasound application

Methodology Applied

Scientific EffectPhase transition: Phase Change

Implementation Method 2

ultrasound-sensitive peptide nanoparticles

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Data Source

PatentUS20260014283A1Ultrasound-sensitive peptide particles for spatially resolved molecule delivery and methods of using the same

Publication Date: 2026.01.15 THE PENN STATE RES FOUND INC

AI summary

Provided herein are compositions comprising cells that each comprise at least one peptide-based nanoparticle. In some embodiments, the peptide-based nanoparticles each comprise a perfluorocarbon liquid core and a plurality of amphiphilic peptides surrounding the perfluorocarbon liquid core. Also provided herein are methods of preparing any of the compositions described herein, as well as methods of cellular tracking using any of the composition described herein.