Self-Assembling Drug Delivery System for HER2+ Targeting

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Solution Overview

Problem

Current targeted therapies for HER2+ breast tumors face challenges such as costly chemical modifications, impaired drug activity, poor penetration into cells, and off-target effects, with existing methods like immunoconjugates and fusion toxins experiencing reduced potency and cardiac toxicity.

Innovation Solution

A self-assembling drug delivery system comprising a polypeptide sequence, a nucleic acid sequence, and a chemical agent linked via electrostatic interactions, utilizing a targeting ligand and an endosomolytic domain to facilitate receptor binding, internalization, and cytosolic penetration, avoiding chemical modifications and leveraging natural ligand affinity for HER2+ cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemical coupling of antibodies to drugs is used (immunoconjugates), then targeted delivery is achieved, but drug activity and antibody activity are impaired and production cost increases

Engineering Contradiction:

Improvetargeted deliveryVSAvoidproduction cost and drug activity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The invention divides the delivery system into separate components: a targeted carrier protein (HerPBK10) and a drug molecule, which self-assemble through non-covalent interactions rather than chemical coupling. This segmentation preserves the integrity and activity of both components while achieving targeted delivery.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The carrier protein HerPBK10 acts as an intermediary that binds to the drug molecule through non-covalent interactions, mediating targeted delivery without requiring chemical modification of either component. This intermediary approach maintains the natural activity of both the carrier and drug.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If recombinant antibodies are used for targeting, then targeted therapy is achieved, but structure is lost in physiological conditions resulting in impaired targeting activity

Engineering Contradiction:

Improvetargeting activityVSAvoidstructural stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention uses a recombinant carrier protein (HerPBK10) with a decalysine motif that is stable in physiological conditions, replacing the use of recombinant antibodies that lose structure. The carrier protein maintains its structure and targeting capability in serum and physiological environments.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Stability of the object's composition

If covalent linkage of drug to carrier is used, then stable conjugate is formed, but activity of both molecules is impaired and production cost increases

Engineering Contradiction:

Improveconjugate stabilityVSAvoidproduction cost and molecular activity

Core Design Contradiction:

Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The carrier protein and drug molecule self-assemble through non-covalent interactions between the decalysine motif and the drug, forming a stable conjugate without requiring chemical coupling reagents or complex manufacturing processes. This self-service approach preserves molecular activity and reduces production cost.

Inventive Principle:

Principle #25Self-service

4Productivity

If standard chemotherapy methods are used, then treatment is achieved, but off-target effects such as heart toxicity occur

Engineering Contradiction:

Improvetreatment efficacyVSAvoidoff-target toxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The carrier protein HerPBK10 is designed with a decalysine motif that provides local positive charge for binding to the negatively charged drug molecule. This localized functional design enables specific binding and targeted delivery, reducing off-target effects while maintaining treatment efficacy.

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 system achieves targeted and efficient delivery of chemotherapeutic agents like doxorubicin to HER2+ breast cancer cells with reduced toxicity to non-target tissues, maintaining drug potency and stability, and preventing cardiac toxicity.

Implementation Method 1

a nucleic acid sequence bound to the polypeptide sequence via electrostatic interactions

Methodology Applied

Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 2

A self-assembling drug delivery system comprising a polypeptide sequence, a nucleic acid sequence, and a chemical agent

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS10391180B2Self-assembling complex for targeting chemical agents to cells

Publication Date: 2019.08.27 CEDARS SINAI MEDICAL CENT

AI summary

The present invention relates to a complex that can be injected into the body to hone in on target cells to deliver molecules. In one embodiment, the invention provides a drug delivery system that includes components that self-assemble into one targeted conjugate. In another embodiment, the invention includes a targeted carrier protein and a nucleic acid sequence non-covalently linked to one or more drugs.