Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 4, Pages 1441-1454Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.04.004
Keywords
Triple negative breast cancer; CD44 targeting; Vitamin E-TPGS; Nano-micelles; Fluorescence imaging of TNBC; Apoptosis
Funding
- Wayne State University
- American Cancer Society [4493533]
- NIH [P30 CA22453]
- Perinatology Research Branch for the services of Microscopy, Imaging and Cytometry Resources (MICR) core
- NSF [0216084]
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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. (C) 2018 Elsevier Inc. All rights reserved.
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