Triple-negative breast cancer (TNBC) is a highly aggressive sub-type of breast cancer. TNBC is characterized by intra-tumor heterogeneities, high proliferative activity, poor prognosis, high risk of relapse, and metastasis to lungs and brain. The effective treatment of TNBC requires a multimodal approach that targets and inhibits multiple essential pathways of tumor growth, invasiveness or metastasis. Nanoparticle-based delivery systems that can carry more than one chemotherapeutic drug or different type of therapeutic agents have shown promising results for the treatment of TNBC. Polysilsesquioxane (PSilQ) nanoparticles have been recently developed for different therapeutic and imaging applications. In particular, porphyrin-based PSilQ nanomaterials have shown encouraging results to improve the photodynamic therapy (PDT) against cancer. The novel strategy consists in developing porphyrin-based PSilQ NPs with high loading of porphyrin molecules and redox-responsive properties to enhance the delivery and biodegradability of the platform. In this work, taking advantages of the chemical and structural properties of PSilQ nanoparticles, we have synthesized, characterized, and applied in TNBC cells a novel multimodal PSilQ-based nanomaterial. The network of this nanomaterial is formed by protoporphyrin IX (PpIX) chemically connected via a redox-responsive linker. Curcumin, an anticancer agent, is co-encapsulated during the microemulsion synthesis of the PSilQ nanoparticles. Moreover, the surface of the nanomaterial is functionalized with polyethyleneimine to carry siRNA. The structural, chemical and photochemical properties of this PSilQ platform were fully characterized. Its ability to generate ROS in TNBC cells was determined. The effectiveness of this multimodal PSilQ nanomaterial for the combined treatment, including chemo, photodynamic and gene therapies, was successfully demonstrated in TNBC cells.

Multimodal polysilsesquioxane nanoparticles for the combined treatment of triple-negative breast cancer using chemo, photodynamic and gene therapies

2019 Spring National Meeting

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