Mito-FF Conjugate Self-Assembly in Carcinoma Mitochondria

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Solution Overview

Problem

Current technologies lack effective methods for inducing cytotoxicity in carcinoma cells while sparing normal cells, particularly through intracellular self-assembly of synthetic peptides targeting mitochondria, which is crucial for treating cancer.

Innovation Solution

A mitochondria-targeting conjugate, Mito-FF, is developed, comprising a triphenylphosphonium moiety for mitochondrial targeting and a dipeptide of phenylalanine as a fiber-forming building block, along with a fluorophore for detecting fibril formation, which self-assembles within carcinoma cells' mitochondria to induce apoptosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If synthetic peptides are designed to self-assemble in mitochondria to induce cytotoxicity in carcinoma cells, then cancer treatment efficacy is improved, but selective targeting of carcinoma cells over normal cells becomes difficult to achieve

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidtoxicity to normal cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The peptide is designed with a mitochondria-targeting moiety (triphenylphosphonium group) that localizes the self-assembly activity specifically within mitochondria of carcinoma cells. This local targeting ensures that the cytotoxic effect is confined to the intended site (carcinoma cell mitochondria) while sparing normal cells, as the peptide only accumulates and assembles in mitochondria with high negative membrane potential characteristic of carcinoma cells.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention exploits the parameter difference in mitochondrial membrane potential between carcinoma cells (high negative potential) and normal cells (reduced potential). The triphenylphosphonium moiety responds to this parameter change by selectively accumulating in mitochondria with high negative potential, thereby enabling selective cytotoxicity in carcinoma cells through self-assembly-induced mitochondrial dysfunction.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If mitochondria-targeting peptides are used to induce apoptosis in carcinoma cells, then cancer cell elimination is improved, but the mechanism for selective accumulation in carcinoma cells versus normal cells needs to be established

Engineering Contradiction:

Improveapoptosis induction efficiencyVSAvoidselective targeting accuracy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The mitochondria-targeting peptide utilizes the inherent negative membrane potential of carcinoma cell mitochondria as an electrochemical gradient to drive its own selective accumulation. The triphenylphosphonium moiety is attracted to the negative potential, enabling the peptide to self-direct to the target site without requiring external guidance mechanisms, thereby achieving both high accumulation efficiency and selective targeting accuracy.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The invention replaces mechanical or biochemical recognition mechanisms with an electrostatic field-based targeting mechanism. Instead of relying on mechanical binding or biochemical signaling for selective targeting, the triphenylphosphonium moiety uses electrostatic attraction to the negative mitochondrial membrane potential to achieve selective accumulation in carcinoma cells, simplifying the targeting mechanism while improving reliability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

Mito-FF selectively induces apoptosis in carcinoma cells by forming fibrils within mitochondria, driven by the negative membrane potential of carcinoma cells, while being non-toxic to normal cells due to reduced mitochondrial accumulation and fibril formation.

Implementation Method 1

a conjugate including a mitochondria-targeting moiety and a peptide molecule capable of self-assembly in mitochondria

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

driven by the negative membrane potential of carcinoma cells

Methodology Applied

Scientific EffectElectrostatic accumulation: Electrostatics

Data Source

PatentUS11083798B2Conjugate including peptide molecule capable of self-assembly in cell organelle and pharmaceutical composition for preventing or treating cancer including conjugate

Publication Date: 2021.08.10 UNIST (ULSAN NAT INST OF SCI & TECH)

AI summary

Disclosed are a conjugate including a mitochondria-targeting moiety and a peptide molecule capable of self-assembly; and a pharmaceutical composition for preventing or treating cancer including the conjugate as an active ingredient.