Corrole Nanoparticles for Tumor MRI and Therapy
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Solution Overview
Problem
Current cancer treatments using porphyrins and macrocyclic compounds have limitations, as their metal complexes, such as Ga(III) derivatives, are unable to penetrate cell membranes without facilitation, making them safe but ineffective for therapeutic use, and existing imaging techniques struggle to detect tumors deep within the body.
Innovation Solution
Development of tumor-targeted protein-based nanoparticles combining metallated corroles like manganese (Mn), iron (Fe), or gallium (Ga) with HerPBK10 molecules, which facilitate penetration and enable both imaging and therapeutic effects, particularly utilizing MRI for deeper tumor detection and treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If metal complexes such as Ga(III) derivatives are used for cancer treatment, then safety at pharmacologic doses is achieved, but ability to penetrate cell membranes is lost
Solution Approach 1:
The patent introduces HerPBK10 peptide as an intermediary facilitator that enables metal complex penetration through cell membranes. The peptide acts as a membrane-lytic molecule that opens transient pathways, allowing the Ga(III) or Mn(III) corrole complexes to enter cells without direct membrane disruption by the complexes themselves, thus maintaining safety while achieving penetration.
Solution Approach 2:
The invention creates a composite system combining metal corrole complexes (Ga(III) or Mn(III)) with HerPBK10 peptide facilitators. This composite approach allows the metal complexes to retain their therapeutic properties while the peptide component provides the membrane-penetration capability, resolving the contradiction between safety and penetration ability.
2Measurement precision
If conventional imaging techniques are used, then current detection capabilities are maintained, but ability to detect tumors deep within the body is lost
Solution Approach 1:
The patent utilizes Mn(III) corrole complexes that exhibit paramagnetic properties, which significantly alter the T1 relaxation time parameter in MRI imaging. This parameter change enables the complexes to act as effective MRI contrast agents, enhancing the detectability of tumors at greater depths compared to conventional imaging techniques.
Solution Approach 2:
The metal corrole complexes serve multiple functions simultaneously: they act as therapeutic agents (Ga(III) for PDT, Mn(III) for catalysis), imaging agents (Mn(III) for MRI), and are delivered via a universal peptide facilitator (HerPBK10). This multi-functionality allows a single system to address both treatment and deep imaging detection needs.
3Reliability
If porphyrins and macrocyclic compounds are used for cancer treatment, then extensive therapeutic investigation has been conducted, but therapeutic potential of newer compounds like corroles has not been fully realized
Solution Approach 1:
The HerPBK10 peptide serves as a universal intermediary that simplifies the delivery complexity of corrole compounds. By using a single peptide facilitator that can deliver multiple types of corrole complexes (Ga(III), Mn(III), Al(III)), the system reduces the overall complexity compared to developing separate delivery mechanisms for each compound type.
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 nanoparticles, such as HerMn, demonstrate significant tumor growth inhibition and imaging capabilities, especially with Mn corroles showing potential as effective MRI agents, allowing for targeted tumor detection and treatment while being safe at pharmacologic doses.
Implementation Method 1
Different concentrations of each corrole were prepared and measured in situ (in a microfuge tube) for T1 relaxation time. Mn corroles showing potential as effective MRI agents
Implementation Method 2
Fe(III) and Mn(III) complexes are very active catalysts for decomposition of reactive oxygen and nitrogen species involved in a variety of relevant diseases
Implementation Method 3
toxic corroles, such as the Ga(III) derivative, are safe at pharmacologic doses but can kill cells when allowed to breach into the cytosol
Data Source
AI summary
Disclosed herein are compositions comprising a targeted corrole nanoparticle; and an acceptable excipient. Also disclosed are compositions comprising a targeted corrole nanoparticle; and an acceptable carrier. Further, disclosed herein are methods of imaging a condition in a subject, comprising providing a composition comprising a targeted corrole nanoparticle; administering an effective amount of the targeted corrole nanoparticle to the subject; and imaging the condition in the subject. In addition, disclosed herein are methods of treating cancer in a subject, comprising providing a composition comprising a targeted corrole nanoparticle; and administering a therapeutically effective dosage of the targeted corrole nanoparticle to the subject.