pH-Sensitive Lipid Nanoparticles for Targeted Drug Delivery

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Solution Overview

Problem

Current treatments for colorectal and head and neck cancers face challenges such as drug resistance and adverse side effects, particularly with irinotecan, and microRNA delivery faces issues like rapid degradation and poor cellular uptake.

Innovation Solution

Development of pH-sensitive lipid nanoparticles modified with cell-penetrating, mitochondria-targeting, and cancer-specific peptides to enhance the delivery of irinotecan and microRNA, allowing for targeted accumulation in tumor environments and improved therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If irinotecan is used to treat colorectal cancer, then therapeutic effect is improved, but drug resistance and side effects worsen

Engineering Contradiction:

Improvetherapeutic effectVSAvoiddrug resistance and side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses pH-sensitive lipid nanoparticles as an intermediary delivery system to transport irinotecan and microRNA to tumor cells. The nanoparticles accumulate in the acidic tumor microenvironment and release their cargo, mediating the therapeutic effect while protecting normal tissues from direct drug exposure and reducing drug resistance through combined delivery of multiple agents

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs composite nanoparticle formulations containing pH-sensitive lipids, PEG peptides, and encapsulated therapeutics (irinotecan and microRNA). This composite structure enables targeted delivery, sustained release, and synergistic therapeutic effects, improving treatment efficacy while reducing side effects through controlled delivery

Inventive Principle:

Principle #40Composite materials

2Reliability

If microRNA is delivered to treat cancer, then therapeutic effect is improved, but rapid degradation and poor cellular uptake worsen

Engineering Contradiction:

Improvetherapeutic effectVSAvoidmicroRNA stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The pH-sensitive lipid nanoparticles serve as a protective intermediary that shields microRNA from degradation in the systemic circulation and facilitates its delivery into cancer cells. The nanoparticle structure prevents enzymatic degradation and enhances cellular uptake through pH-dependent release mechanisms

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes pH parameter changes between normal tissue (pH 7.4) and tumor microenvironment (pH 6.5-6.8) to control microRNA release. The pH-sensitive lipid composition undergoes structural changes at acidic pH, enabling targeted release of microRNA at the tumor site while maintaining stability during circulation

Inventive Principle:

Principle #35Parameter changes

3Reliability

If nanoparticle targets tumor cells, then therapeutic efficacy is improved, but distinction between normal and cancer cells worsens

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidtoxicity to normal tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent imparts local quality to the nanoparticle surface by conjugating pH-sensitive PEG peptides that specifically interact with tumor cell surfaces or the acidic tumor microenvironment. This localized modification enables selective accumulation in tumors through enhanced permeability and retention (EPR) effect and pH-dependent binding, sparing normal tissues from drug toxicity

Inventive Principle:

Principle #3Local quality

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 pH-sensitive lipid nanoparticles effectively reduce drug resistance and side effects by enhancing irinotecan and microRNA delivery to cancer cells, leading to improved treatment outcomes for colorectal and head and neck cancers with reduced toxicity to normal tissues.

Implementation Method 1

pH-sensitive lipid nanoparticle, comprising a surface of the nanoparticle core, wherein the surface comprising an imine-omPEG, the imine is a pH-sensitive linker

Methodology Applied

Scientific EffectpH-sensitive response:

Implementation Method 2

the RF peptide is a potent cell-penetrating peptide

Methodology Applied

Scientific EffectCell-penetrating peptide mechanism:

Implementation Method 3

the K peptide is a mitochondria-targeting peptide

Methodology Applied

Scientific EffectMitochondria-targeting:

Implementation Method 4

the H peptide is a cancer specific binding peptide

Methodology Applied

Scientific EffectCancer-specific binding:

Data Source

PatentUS11141491B2PH-sensitive lipid nanoparticles for encapsulation of anticancer drugs and microRNA and use thereof

Publication Date: 2021.10.12 NAT YANG MING CHIAO TUNG UNIV

AI summary

Currently, the present invention provides a pH-sensitive lipid nanoparticle, comprising: a nanoparticle core composed of a mixture of lipid and/or surfactant, and the surface of the nanoparticle core comprising: a imine-omPEG, the imine is a pH-sensitive linker; and a PEG-peptide, wherein the peptide is selected from the group consisting of a RF peptide, a K peptide, and a H peptide; wherein the RF peptide is a potent CPP, the K peptide is a mitochondria-targeting peptide and the H peptide is a cancer specific binding peptide; a lipid, inside the nanoparticle core; wherein the lipid nanoparticle encapsulating a targeting agent.