Format

Send to

Choose Destination
Pharmaceutics. 2019 May 5;11(5). pii: E216. doi: 10.3390/pharmaceutics11050216.

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

Author information

1
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel. ravited@technion.ac.il.
2
The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 3200000, Israel. assaraf@technion.ac.il.
3
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel. Anton.Slavkin@Strauss-Group.com.
4
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel. tdolev@gmail.com.
5
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel. talshahar77@gmail.com.
6
The Lab of Biopolymers for Food and Health, Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 3200000, Israel. livney@technion.ac.il.

Abstract

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.

KEYWORDS:

CD44-targeted chemotherapy; Maillard conjugates; hyaluronic acid; ovarian cancer; serum albumin; theranostic nanoparticles

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center