Abstract
Triple negative breast cancer (TNBC) is a highly aggressive tumor subtype, lacking estrogen, progesterone and human epidermal growth factor-2 (HER-2) receptors. Thus, early detection and targeted therapy of TNBC is an urgent need. Herein, we have developed a CD44 targeting Hyaluronic Acid (HA) decorated biocompatible oligomer, containing FDA approved vitamin E TPGS and Styrene Maleic Anhydride (SMA) (HA-SMA-TPGS) for targeting TNBC. The self-assembling HA-SMA-TPGS was encapsulated with poorly water soluble, potent curcumin analogue (CDF) to form nanomicelles (NM), HA-SMA-TPGS-CDF has demonstrated excellent nanoparticle characteristics for parenteral delivery. The targeted NM can selectively kill TNBC cells through CD44 mediated apoptosis pathway. Tumor imaging using phase-2 clinical trial near infrared (NIR)-fluorescent dye (S0456) conjugate, HA-SMA-TPGS-S0456 showed excellent TNBC tumor accumulation with minimum liver and spleen uptake. To our best of knowledge, for the first time, we are reporting a promising platform for CD44 mediated multimodal NIR imaging and cytotoxin delivery to TNBC.
This image indicates the development of CD44 selective HA-SMA-TPGS oligomer and encapsulation of CDF to form HA-SMA-TPGS-CDF nano-micelle. The HA-SMA-TPGS oligomer was ligated with near infrared dye for imaging of TNBC. The HA-SMA-TPGS-CDF showed significantly higher tumor cell killing effect as compared to SMA-TPGS or CDF treatment through up-regulation of tumoricidal PTEN protein and down-regulation of tumorigenic NF-κB protein, resulting in induction of apoptosis. The cell uptake study of HA-SMA-TPGS-rhodamine demonstrates TNBC cell selective endocytosis. Overall the purpose of study is to demonstrate CD44 selective TNBC imaging and pronounced cell killing. [Display omitted]