Nanocomplexes to treat prostate cancer

Background

Nanoparticle-based drug delivery systems have emerged as a transformative approach in the fields of oncology, diagnostics, and targeted therapy. These systems leverage the unique properties of nanoscale materials—such as enhanced permeability and retention (EPR) effect, tunable surface chemistry, and the ability to encapsulate diverse therapeutic or imaging agents—to improve the delivery and efficacy of drugs that are otherwise limited by poor solubility, rapid degradation, or off-target toxicity. Particularly in cancer treatment, the need for more effective and selective delivery vehicles is acute, as conventional chemotherapeutics often suffer from systemic side effects and limited accumulation at tumor sites. Metal ion-ligand complexes, including those formed with transition or noble metals, hold significant promise for both therapeutic and diagnostic applications due to their potent biological activities and imaging capabilities.

Despite their potential, current approaches to formulating metal ion-ligand complexes face substantial challenges. Many clinically relevant complexes, such as those involving disulfiram and copper, exhibit poor water solubility and instability in physiological environments, which severely restricts their bioavailability and therapeutic index. Traditional methods for nanoparticle preparation, such as film-dispersion or solvent evaporation, often require toxic organic solvents like DMSO, result in low drug loading efficiencies, and produce particles with broad and uncontrolled size distributions. These limitations hinder scalability, reproducibility, and clinical translation. Furthermore, the inability to co-load multiple agents or to achieve stable, high-concentration formulations restricts the use of such systems in combination therapies or theranostic applications, where simultaneous delivery of drugs and imaging agents is desirable. As a result, there remains a critical unmet need for robust, scalable, and biocompatible methods to prepare stable, high-loading metal ion-ligand nanocomplexes suitable for clinical use.

Technology

This technology provides a robust and scalable platform for creating stabilized metal ion-ligand nanocomplexes, designed for therapeutic and diagnostic applications. The process involves combining a ligand—such as a therapeutic drug, imaging agent, or photosensitizer—with a metal salt (including transition, noble, or radioactive metals) in a solution containing an FDA-approved stabilizer. Mixing is typically performed using devices like microfluidics or vortex mixers, and the resulting nanoparticles are isolated without the use of toxic solvents like DMSO. The method achieves high drug loading efficiency, tunable particle sizes (generally 10–250 nm), and excellent stability in biological media. The platform supports co-loading of multiple agents and surface modification with targeting ligands, enabling combination therapies and targeted delivery. The nanoparticles can be lyophilized for long-term storage and reconstituted without loss of function, and the technology is adaptable to a wide range of ligands, metals, and stabilizers.

What differentiates this technology is its unique combination of versatility, efficiency, and clinical practicality. Unlike traditional methods that often suffer from low drug loading, poor stability, and reliance on toxic solvents, this approach enables nearly 100% drug loading and high drug concentrations, while maintaining nanoparticle stability in serum and during storage. Its compatibility with a broad spectrum of ligands (including poorly soluble drugs), metals, and FDA-approved stabilizers allows for customization to specific therapeutic or diagnostic needs. The use of microfluidics and other scalable mixing methods ensures precise control over particle size and distribution, optimizing delivery for passive tumor targeting via the enhanced permeability and retention (EPR) effect. Furthermore, the ability to co-load multiple agents and attach targeting moieties opens the door to advanced combination therapies and theranostic applications, making this solution highly adaptable for cancer treatment, infectious disease management, and image-guided interventions.

Benefits

• High drug loading efficiency approaching 100%, enabling effective therapeutic dosing.
• Tunable nanoparticle size (10–250 nm) optimized for enhanced tumor targeting via the EPR effect.
• Excellent stability in biological media and during storage, ensuring consistent performance.
• Versatile formulation allowing co-loading of multiple agents (therapeutics, imaging agents, photosensitizers) for combination therapy and theranostics.
• Use of FDA-approved stabilizers and avoidance of toxic solvents like DMSO, improving safety and regulatory compliance.
• Scalable and cost-effective manufacturing compatible with various mixing technologies including microfluidics.
• Capability for surface modification with targeting ligands to enable active targeting of diseased tissues.
• Demonstrated potent anticancer activity, including efficacy against drug-resistant cancer cells, via novel mechanisms such as paraptosis.

Applications

• Targeted anticancer drug delivery
• Theranostic nanoparticles for imaging
• Combination therapy nanoparticles
• Radioisotope-based diagnostic imaging
• Image-guided cancer surgery

Additional info

These are stabilized metal ion-ligand nanocomplexes, formed by combining a ligand (therapeutic, imaging, or photosensitizer) and a metal salt with an FDA-approved stabilizer. The solvent-free process yields tunable nanoparticles (10-250 nm) with high payload capacity and enhanced biological stability. They facilitate co-loading for advanced therapeutic and diagnostic applications.