CD44 directed nanomicellar payload delivery platform for selective anticancer effect and tumor specific imaging of triple negative breast cancer

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.