Cationic Polymer Coated Mesoporous Silica Nanoparticles for Tumor Targeting

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Solution Overview

Problem

Current nanocarrier drug delivery systems face challenges such as rapid sequestration by the reticuloendothelial system, colloidal instability, and inefficient intracellular drug delivery, leading to low tumor targeting and drug accumulation, with less than 10% of the administered dose reaching the tumor site effectively.

Innovation Solution

Development of submicron structures with a silica body and cationic polymer coating, capable of encapsulating therapeutic compounds and siRNA, which are designed to reduce particle opsonization and enhance passive targeting to tumors, utilizing size reduction and surface functionalization to improve biodistribution and drug delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nanocarrier drug delivery systems are used, then drug delivery capability is provided, but rapid sequestration by the reticuloendothelial system occurs leading to low tumor accumulation

Engineering Contradiction:

Improvedrug delivery efficiencyVSAvoidreticuloendothelial system sequestration

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the surface charge parameter of nanocarriers by coating with cationic polymers (changing from negative to positive charge). This parameter change reduces recognition and uptake by the reticuloendothelial system, thereby extending circulation time and improving tumor accumulation while maintaining drug delivery capability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite nanocarrier structures combining silica cores with cationic polymer coatings. This composite material approach provides both the structural integrity needed for drug delivery and the surface properties that reduce reticuloendothelial system sequestration, achieving improved tumor accumulation

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If conventional nanocarriers are used, then drug encapsulation is achieved, but colloidal instability occurs leading to aggregation

Engineering Contradiction:

Improvedrug encapsulation capacityVSAvoidcolloidal stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the surface charge parameter from negative to positive through cationic polymer coating. This parameter modification enhances colloidal stability by reducing electrostatic attraction between particles, preventing aggregation while maintaining drug encapsulation capacity

Inventive Principle:

Principle #35Parameter changes

3Productivity

If nanocarriers are administered, then drug delivery to tumor is attempted, but less than 10% of administered dose reaches tumor site effectively

Engineering Contradiction:

Improvetumor targeting efficiencyVSAvoiddrug delivery loss

Core Design Contradiction:

ProductivityVSLoss of energy

Solution Approach 1:

The patent modifies the surface charge parameter to positive, which reduces clearance by the reticuloendothelial system and extends circulation time. This parameter change increases the fraction of administered dose that reaches the tumor site through enhanced passive targeting, improving tumor targeting efficiency and reducing drug delivery loss

Inventive Principle:

Principle #35Parameter changes

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 submicron structures achieve effective passive tumor targeting and enhanced drug delivery, with up to 12% of the injected dose accumulating at the tumor site, inducing apoptosis and reducing systemic side effects, while maintaining minimal cytotoxicity and improved drug efficacy.

Implementation Method 1

a cationic polymer on the surface of said silica body

Methodology Applied

Scientific EffectElectrostatic interactions: Electrostatics

Data Source

PatentUS10343903B2Cationic polymer coated mesoporous silica nanoparticles and uses thereof

Publication Date: 2019.07.09 RGT UNIV OF CALIFORNIA

AI summary

A submicron structure having a silica body defining a plurality of pores is described. The submicron body may be spherical or non-spherical, and may include a cationic polymer or co-polymer on the surface of said silica body. The submicron structure may further include an oligonucleotide and be used to deliver the oligonucleotide to a cell. The submicron structure may further include a therapeutic agent and be used to deliver the therapeutic agent to a cell. An oligonucleotide and therapeutic agent may be used together. For example, when the oligonucleotide is an siRNA, the composition may be used to decrease cellular resistance to the therapeutic agent by decreasing translation of a resistance gene.