Magnetic Nanoparticle Adenovirus Complex for CAR-Independent Tumor Delivery

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Solution Overview

Problem

Current cancer gene therapy using adenovirus (Ad) faces limitations due to dependence on the coxsackievirus and adenovirus receptor (CAR) for target cell entry, leading to poor transduction efficiency in CAR-negative tumors, and existing modifications with cationic polymers or lipids result in non-specific dissemination to surrounding tissues.

Innovation Solution

A composition combining antitumor adenovirus with cross-linked PEGylated magnetic nanoparticles and catechol-grafted poly-L-lysine, which is directed to tumor cells using an external magnetic field, enhancing transduction efficiency and targeted delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If adenovirus is used for cancer gene therapy, then high transduction efficiency in dividing and non-dividing cells is achieved, but transduction efficiency in CAR-negative tumors is poor

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidapplicability to CAR-negative tumors

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses magnetic nanoparticles as an intermediary carrier to deliver adenovirus to tumor cells. The magnetic nanoparticles complex with the adenovirus and enable magnetic field-directed delivery, serving as a mediator that bypasses the need for CAR receptor interaction while maintaining transduction efficiency.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite delivery system combining magnetic nanoparticles with adenovirus particles. This composite structure integrates the targeting capability of magnetic nanoparticles with the transduction capability of adenovirus, enabling enhanced delivery to both CAR-positive and CAR-negative tumors through magnetic field guidance.

Inventive Principle:

Principle #40Composite materials

2Reliability

If adenovirus surface is modified with cationic polymers or lipids, then gene delivery efficiency is enhanced, but non-specific dissemination to surrounding non-target tissues occurs

Engineering Contradiction:

Improvegene delivery efficiencyVSAvoidnon-specific dissemination to non-target tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Magnetic nanoparticles serve as an intermediary delivery vehicle that can be externally controlled. The adenovirus is complexed with magnetic nanoparticles, allowing the magnetic field to direct the complex specifically to the tumor site, thereby preventing non-specific dissemination while maintaining enhanced gene delivery efficiency.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The magnetic field acts as a counteracting force against the natural diffusion and non-specific distribution of the virus. By applying an external magnetic field, the system counterbalances the tendency toward non-specific dissemination and redirects the viral complexes specifically to the target tumor tissue.

Inventive Principle:

Principle #8Anti-weight (Counterweight)

3Reliability

If magnetic nanoparticles are used for targeted delivery, then specific delivery to target tissues and enhanced cellular uptake is achieved, but system complexity increases

Engineering Contradiction:

Improvespecific delivery to target tissuesVSAvoiddelivery system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The magnetic nanoparticle system serves multiple functions: it acts as a delivery carrier, a targeting agent responsive to external magnetic fields, and a means to enhance cellular uptake. This multi-functionality reduces the need for separate components, thereby managing system complexity while achieving specific targeted delivery.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system allows for adjustment of magnetic field parameters (strength, gradient, timing) to optimize delivery without changing the fundamental structure of the nanoparticle-virus complex. This parameter-based control provides flexibility in managing delivery specificity while keeping the physical system relatively simple.

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

Significantly increases the transduction efficiency of antitumor adenovirus into tumor cells, achieving enhanced antitumor effects by facilitating CAR-independent entry and reducing liver tropism, thereby improving cancer treatment efficacy.

Implementation Method 1

A composition combining antitumor adenovirus with cross-linked PEGylated magnetic nanoparticles and catechol-grafted poly-L-lysine, which is directed to tumor cells using an external magnetic field

Methodology Applied

Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

magnetofection with PEI-coated superparamagnetic iron oxide nanoparticle-coated Ad can provide a strong platform for efficient and safe delivery of therapeutic genes

Methodology Applied

Scientific EffectMagnetofection:

Data Source

PatentUS11000590B2Virus-PCION complex having enhanced antitumor effect by using electromagnetic field

Publication Date: 2021.05.11 GENEMEDICINE CO LTD

AI summary

The present disclosure relates to a composition for transduction of a virus in a cell by using a crosslinked product of PEGylated magnetic nanoparticles and catechol grafted poly-L-lysine by application of an external magnetic field. When the composition is used, a virus may be delivered into cells more rapidly and efficiently than in intracellular uptake of a virus by CAR-mediated endocytosis.