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Open AccessArticle

Developing Body-Components-Based Theranostic Nanoparticles for Targeting Ovarian Cancer

1
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel
2
The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 3200000, Israel
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 216; https://doi.org/10.3390/pharmaceutics11050216
Received: 16 March 2019 / Revised: 20 April 2019 / Accepted: 23 April 2019 / Published: 5 May 2019
(This article belongs to the Special Issue Hyaluronic Acid for Biomedical Applications)
Ovarian cancer mortality is the highest among gynecologic malignancies. Hence, the major challenges are early diagnosis and efficient targeted therapy. Herein, we devised model theranostic nanoparticles (NPs) for combined diagnostics and delivery of chemotherapeutics, targeted to ovarian cancer cells. These NPs were made of natural biocompatible and biodegradable body components: hyaluronic acid (HA) and serum albumin (SA). The hydrophilic HA served as the targeting ligand for cancer cells overexpressing CD44, the HA receptor. SA, the natural carrier of various ligands through the blood, served as the hydrophobic block of the self-assembling block copolymeric Maillard-conjugates. We show the successful construction of fluorescently-labeled SA-HA conjugate-based theranostic NPs, their loading with paclitaxel (PTX) (association constant (8.6 ± 0.8) × 103 M−1, maximal loading capacity of 4:1 PTX:BSA, and 96% encapsulation efficiency), selective internalization and cytotoxicity to CD44-overexpressing ovarian cancer cells (IC50: 26.4 ± 2.3 nM, compared to 115.0 ± 17.4 of free PTX, and to 58.6 ± 19.7 nM for CD44-lacking cognate ovarian cancer cells). Fluorescein isothiocyanate (FITC) was used for in vitro imaging, whereas long wavelength fluorophores or other suitable tracers would be used for future in vivo diagnostic imaging. Collectively, our findings demonstrate that fluorescent HA-SA NPs harboring a cytotoxic drug cargo can specifically target, label CD44-expressing ovarian cancer cells and efficiently eradicate them. View Full-Text
Keywords: hyaluronic acid; serum albumin; Maillard conjugates; theranostic nanoparticles; CD44-targeted chemotherapy; ovarian cancer hyaluronic acid; serum albumin; Maillard conjugates; theranostic nanoparticles; CD44-targeted chemotherapy; ovarian cancer
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MDPI and ACS Style

Edelman, R.; Assaraf, Y.G.; Slavkin, A.; Dolev, T.; Shahar, T.; Livney, Y.D. Developing Body-Components-Based Theranostic Nanoparticles for Targeting Ovarian Cancer. Pharmaceutics 2019, 11, 216.

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