Activatable Cell Penetrating Peptide for Targeted Drug Delivery
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Solution Overview
Problem
Current methods for delivering therapeutic and imaging agents into cells, particularly for cancer treatment and diagnosis, face challenges due to the selective barrier function of cell membranes, which hinders the entry of exogenous materials, and existing technologies lack effective personalized approaches for tumor detection and treatment.
Innovation Solution
Development of activatable cell penetrating peptides (ACPPs) with specific sequences and linkers that allow targeted delivery of therapeutic agents and imaging agents into cells by exploiting enzymatic cleavage at tumor sites, enhancing tumor contrast and reducing tumor growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell membranes maintain their selective barrier function to prevent uncontrolled entry of substances, then cell viability is maintained, but delivery of therapeutic agents and imaging markers into cells becomes difficult
Solution Approach 1:
The patent uses cell-penetrating peptides (CPPs) as intermediary carriers to facilitate the transport of therapeutic agents and imaging markers across the cell membrane. The CPPs bind to the cargo molecules and mediate their entry into cells through endocytosis or direct translocation, solving the contradiction by providing a controlled delivery mechanism that respects the membrane's barrier function while enabling necessary drug delivery
Solution Approach 2:
The patent employs enzyme-cleavable linkers that change the molecular parameters of the conjugate in response to specific enzymatic environments (e.g., tumor-associated proteases). The linkers are designed to be stable under normal physiological conditions but undergo cleavage when exposed to tumor-specific enzymes, thereby activating drug release only at the target site and maintaining cell viability elsewhere
2Quantity of substance
If conventional delivery methods are used to administer therapeutic agents systemically, then broad distribution is achieved, but lack of targeted delivery reduces treatment efficacy and increases side effects
Solution Approach 1:
The patent implements a pre-targeting strategy where cell-penetrating peptides are administered first to accumulate at tumor sites and bind to tumor-associated markers. Subsequently, the therapeutic agents are administered and are rapidly taken up by the pre-positioned CPPs at the tumor site. This preliminary action ensures targeted delivery and maximizes treatment efficacy while minimizing systemic exposure
Solution Approach 2:
The patent extracts the targeting function from the therapeutic agent itself and separates it into a distinct cell-penetrating peptide component. This allows the CPP to independently navigate to the tumor site and bind to markers, while the therapeutic cargo remains separate until activation, enabling independent optimization of both targeting and therapeutic functions
3Measurement precision
If tumor markers are used for targeted delivery, then specificity to tumor cells is improved, but heterogeneity of marker expression across different tumors reduces universality of the approach
Solution Approach 1:
The patent uses a universal cell-penetrating peptide framework that can recognize and bind to multiple different tumor-associated markers including PSMA, CEA, and other proteases. The CPP structure is designed to accommodate various targeting moieties, making it a multi-functional platform that can be adapted to different tumor types and marker expressions while maintaining the same delivery mechanism
Solution Approach 2:
The patent employs dynamic, modular conjugate structures where the cell-penetrating peptide, linker, and therapeutic cargo can be reconfigured based on the specific tumor type and marker expression. The system adapts its configuration to match the target tumor characteristics, providing versatility across different cancer types while maintaining targeted delivery efficacy
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 ACPPs enable enhanced delivery of therapeutic agents and improved imaging capabilities, leading to increased survival rates and more accurate tumor detection, thereby addressing the limitations of existing technologies in cancer treatment and diagnosis.
Implementation Method 1
peptide B with a sequence comprising 5 to 20 consecutive basic amino acids
Implementation Method 2
X is a first enzyme-cleavable linker; Y is a second enzyme-cleavable linker
Data Source
AI summary
Disclosed herein, the invention pertains to methods and compositions that find use in treatment, diagnosis, prognosis and characterization of disease and disease samples based on the ability of a disease sample to cleave a MTS molecule of the present invention. The MTS molecules of the present invention have a formula as disclosed herein and wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X and Y are linkers; P is a pre-targeting moiety; M is a macromolecular carrier, C is a detectable moiety; and T is a compound for delivery to a target, including for example a therapeutic compound.