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Int. J. Mol. Sci. 2018, 19(3), 838; https://doi.org/10.3390/ijms19030838

Copper-Free ‘Click’ Chemistry-Based Synthesis and Characterization of Carbonic Anhydrase-IX Anchored Albumin-Paclitaxel Nanoparticles for Targeting Tumor Hypoxia

1
Use-Inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA
2
Molecular Imaging Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 9 January 2018 / Revised: 11 February 2018 / Accepted: 5 March 2018 / Published: 13 March 2018
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine)
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Abstract

Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors. Toward this, we developed a Carbonic Anhydrase IX (CA IX) receptor targeting human serum albumin (HSA) carriers to deliver the potent anticancer drug, Paclitaxel (PTX). We used Acetazolamide (ATZ), a small molecule ligand of CA IX to selectively deliver HSA-PTX in TNBC cells. A novel method of synthesis involving copper free ‘click’ chemistry (Dibenzocyclooctyl, DBCO) moiety with an azide-labeled reaction partner, known as Strain-Promoted Alkyne Azide Cycloaddition (SPAAC) along with a desolvation method for PTX loading were used in the present study to arrive at the CA IX selective nano-carriers, HSA-PTX-ATZ. The anticancer effect of HSA-PTX-ATZ is higher compared to HSA, PTX and non-targeted HSA-PTX in MDA-MB-231 and MDA-MB-468 cells. The cell killing effect is associated with induction of early and late phases of apoptosis. Overall, our proof-of-concept study shows a promising avenue for hypoxia-targeted drug delivery that can be adapted to several types of cancers. View Full-Text
Keywords: carbonic anhydrase IX; tumor hypoxia targeting; paclitaxel; copper free ‘click’ chemistry; triple negative breast cancer; albumin nanoparticles; human serum albumin carbonic anhydrase IX; tumor hypoxia targeting; paclitaxel; copper free ‘click’ chemistry; triple negative breast cancer; albumin nanoparticles; human serum albumin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Tatiparti, K.; Sau, S.; Gawde, K.A.; Iyer, A.K. Copper-Free ‘Click’ Chemistry-Based Synthesis and Characterization of Carbonic Anhydrase-IX Anchored Albumin-Paclitaxel Nanoparticles for Targeting Tumor Hypoxia. Int. J. Mol. Sci. 2018, 19, 838.

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