Background

The main problem with chemotherapy is non-selectivity. This non-selectivity leads to the death of both cancer and normal cells, leading to severe adverse side effects such as bone marrow depression, neuropathy, nephropathy, GIT disorders and Hair loss. Doxorubicin (DOX), a common hemotherapeutic agent used for the treatment of various cancers such as breast, lung and ovarian cancer. DOX is an anthracyline drug that possesses potent anticancer activity. The clinical use of DOX remains limited due to its fatal side effects, the most noted being its dose-dependent Cardiotoxicity. Besides its cardiotoxicity, DOX also suffers from having a short half-life, a rapid elimination from the bloodstream, and as a result low bioavailability at tumor site. This low bioavailability allows only partial treatment to occur leaving some cancer cells to survive. These remaining cells mutate and become unresponsive to DOX, a phenomenon known as cancer resistance. Cancer resistance is a defense mechanism developed by cancer cells toward various chemotherapies and represents another obstacle limiting DOX’s clinical use. Cancer Resistance and systemic toxicity represent the main cause behind chemotherapy failure which complicates cancer curability and leads to cancer progression.

An alternative delivery vehicle is needed that can selectively target and kill cancer cells while improving DOX’s efficiency and limiting its associated toxicity.

Technology Overview

This invention entails developing (Nanoparticle)-based combinatorial therapy composed of DOX loaded on core-shell silver/ polymeric (PVA, PEG, and PVP) Nanoparticles. These nanoparticles possess a synergistic anticancer action, ascribed to the multiple killing mechanisms developed by the combined effect of both DOX and Silver.

The nanoparticles small size provides targeted drug delivery via passive targeting. Passive targeting is based on the enhanced permeability and retention (EPR) effect; a characteristic property of malignant tumors ascribed to their leaky blood vessels and poor lymphatic drainage. EPR is attributed to the improper angiogenesis developed by malignant tumor in order to obtain the required nutrients to compensate its rapid proliferation. As a result, these leaky blood vessels are highly porous allowing small and high molecular weight molecules such as NPs to pass through and accumulate at the tumor site. This targeted drug delivery system allows selective killing of cancer cells, causing little or no harm to neighboring normal cells and increases the drug’s bioavailability at the tumor site. This helps reduce the drug’s adverse side effects and aids in prolonging its half-life increasing its overall therapeutic efficacy. These combined factors have allowed a massive reduction (96%) in the standard dose of DOX reducing its dose-dependent toxicity without compromising its anticancer efficiency.

Stage of Development:

• In-vitro testing on breast cancer cell line (MCF-7) and normal cell line.

Related Publications:

Nancy M. Elbaz et al. 2016. Core-Shell Silver/Polymeric Nanoparticles-Based Combinatorial Therapy against Breast Cancer In-vitro. Scientific Reports volume 6, Article number: 30729 

Benefits

Synergic anticancer action ascribed to the multiple killing mechanisms of DOX & Silver NPs.

• 96% lower dose of DOX can be used while maintaining its therapeutic efficiency.
• Reduced dose-dependent Cardiotoxicity.
• Selective cancer cell targeting with fewer side effects.
• Increased bioavailability at tumor site & less elimination prolonging DOX’s half-life.
• Overcome cancer resistance and treatment failure.

Applications

A combinatorial Nanoparticle therapy based on using Silver Nanoparticles along with Chemotherapeutic agent Doxorubicin (DOX) to treat breast cancer.

Opportunity

• Available for exclusive and non-exclusive licensing
• Exclusive/non-exclusive evaluation for defined period (set up for options).
• Collaborative/supportive research