Successful cancer treatment demands that drugs are delivered to the right place at the right time, without causing significant collateral damage in order to achieve a sufficient therapeutic index.  Many systems are being developed as intravascular carriers to enhance tissue-specific drug delivery.  However, the biological barriers inside the body pose a great challenge to achieve this goal. The nanoporous silicon-based multi-stage vectors (MSV) were designed to accomplish the simultaneous objectives of deploying molecularly targeted therapeutic payloads, while also achieving a high degree of penetration across the multiple, sequential biological barriers which adversely affect the body distribution of all agents of therapy, drugs and nano-carriers alike. We have demonstrated highly reproducible manufacturing techniques and cGMP production capability for the MSV, and the complete, harmless, and time-tailored degradation of their components.   We have extensively studied the subcellular trafficking and transport properties of the MSV and their sub-components, demonstrating in particular their ability to deploy their payload in the cell cytoplasm, where most therapeutic agents are required for therapeutic action.  We have also demonstrated the ability to decorate the first-stage of the MSV with targeting moieties that improve their biodistribution.  While personalized therapy is being pursued in the medical world for cancer treatment, we have achieved personalized cancer tissue-specific drug delivery with nano-vectors.  The use of chemotherapy drug-containing MSV for the treatment of triple-negative breast cancer in immunodeficient mice will be demonstrated. Systemic delivery of MSV-siRNA in animal models of human cancers will also be discussed.

Multi-stage vectors for personalized cancer therapy

248th National Meeting (2014)

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