Graphene based theranostics for tumor targeted drug/gene delivery and imaging

Inventors

Mohapatra, SubhraWang, Chunyan

Assignees

University of South FloridaUniversity of South Florida St Petersburg

Publication Number

US-9675714-B1

Publication Date

2017-06-13

Expiration Date

2034-02-21

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Abstract

Disclosed herein are theranostic nanoparticles configured for simultaneous delivery of a diagnostic moiety, drug moiety, and a gene therapy moiety. In one embodiment, the theranostic nanoparticles contain a super paramagnetic iron oxide chemotherapeutic loaded on a chitosan functionalized 2D graphene sheet with a gene therapy moiety attached to the surface of the chitosan functionalized 2D graphene sheet. Also disclosed are methods for making and administering theranositic nanoparticles configured for simultaneous delivery of a diagnostic moiety, drug moiety, and a gene therapy moiety.

Core Innovation

The invention discloses theranostic nanoparticles configured for simultaneous delivery of a diagnostic moiety, drug moiety, and a gene therapy moiety. In particular, these nanoparticles comprise a chemically reduced graphene sheet functionalized with chitosan, loaded with a magnetic resonance imaging (MRI) contrast agent (such as superparamagnetic iron oxide), a chemotherapeutic agent, and a DNA plasmid. The chemotherapeutic agent and gene therapy moiety are both attached directly or loaded onto the graphene sheet, allowing for combination therapy and diagnostic imaging in a single platform.

The problem addressed by this invention is the inefficiency and toxicity associated with current cancer therapies, particularly the inability of traditional drug/gene delivery methods to co-deliver therapeutic and gene agents effectively to the same cells, and the resulting need for higher doses that increase toxic side effects. Existing systems often require separate delivery of chemotherapeutics and gene therapies, leading to suboptimal localization and elevated risk to healthy tissues. There is also a lack of platforms that permit non-invasive, in vivo monitoring of therapeutic efficacy.

This single nanoplatform efficiently combines targeted drug and gene delivery with real-time diagnostic monitoring. The nanoparticles can be functionalized for improved biocompatibility, controlled drug/gene release, and incorporation of targeting moieties for tissue- or cell-specific delivery. By integrating a diagnostic agent, it enables non-invasive, in vivo monitoring (such as through MRI imaging) of drug/gene delivery and therapeutic efficacy, potentially allowing clinicians to tailor therapies based on actual tumor response.

Claims Coverage

There are three independent claims, each specifying distinct inventive features involving nanoparticles, their formulation, and their method of manufacture.

Nanoparticle comprising functionalized chemically reduced graphene with combined therapeutic, diagnostic, and gene delivery components

The nanoparticle consists of: - A chemically reduced graphene sheet - Chitosan attached to or loaded onto the graphene sheet - A magnetic resonance imaging (MRI) contrast agent attached to or loaded onto the graphene sheet - A chemotherapeutic agent attached to or loaded onto the graphene sheet - A DNA plasmid attached to or loaded onto the graphene sheet

Theranostic formulation with functionalized graphene-based nanoparticles and pharmaceutically acceptable carrier

A theranostic formulation includes: - A nanoparticle as above (with a chemically reduced graphene sheet, chitosan, MRI contrast agent, chemotherapeutic agent, and DNA plasmid all attached/loaded onto the graphene) - A pharmaceutically acceptable carrier for administration

Method for generating theranostic nanoparticles enabling combined delivery and imaging

The method comprises: 1. Reducing a graphene oxide sheet to obtain a chemically reduced graphene oxide sheet 2. Loading or attaching a magnetic resonance imaging (MRI) contrast agent onto the sheet 3. Loading or attaching chitosan onto the sheet 4. Loading or attaching a chemotherapeutic agent onto the sheet 5. Loading or attaching a DNA plasmid moiety onto the sheet

In summary, the inventive features are the design of a multifunctional graphene-based nanoparticle integrating drug, gene, and MRI agent; the inclusion of such nanoparticles in a pharmaceutical formulation; and methods for their generation with combined therapeutic and diagnostic functionality.

Stated Advantages

Provides a single nanoplatform for combined delivery of drug and gene therapy moieties, improving co-localization and therapeutic efficacy.

Enables non-invasive, in vivo monitoring of therapeutic efficacy through the diagnostic (MRI contrast) component.

Reduces toxic side effects by targeting and controlled delivery, potentially allowing lower dosages compared to separate administration.

Improves entrapment efficiency of drug compounds compared to previous nanoparticle approaches.

Allows for targeted delivery by addition of specific targeting moieties, enhancing tumor specificity and reducing impact on healthy tissue.

Documented Applications

Antitumor therapeutic application—simultaneous delivery of anticancer drugs and gene therapies to tumors for combined treatment and imaging.

Enabling non-invasive monitoring of cancer therapy efficacy through MRI or CT imaging after nanoparticle administration.

Potential applications as antibacterial and antiviral theranostic agents combining treatment and diagnostic capability.

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