Research Article For reprint orders, please contact: reprints@futuremedicine.com Lactoferrin-tagged quantum dots-based theranostic nanocapsules for combined COX-2 inhibitor/herbal therapy of breast cancer Ahmed S AbdElhamid 1,2 , Dina G Zayed 1,3 , Maged W Helmy 1,4 , Shaker M Ebrahim 5 , Mohammed Bahey-El-Din 6 , Esmat A Zein-El-Dein 2 , Sanaa A El-Gizawy 2 & Ahmed O Elzoghby* ,1,7,8 1 Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt 2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt 3 Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt 4 Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University, El Bahira, Egypt 5 Department of Materials Science, Institute of Graduate Studies & Research, Alexandria University, Alexandria, Egypt 6 Department of Microbiology & Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt 7 Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA 8 Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA *Author for correspondence: Tel.: +1 781 366 8703; Fax: +1 781 366 8703; aelzoghby@bwh.harvard.edu Aim: Herein, tumor-targeted quantum dots (QDs)-based theranostic nanocapsules (NCs) coloaded with celecoxib and honokiol were developed. Materials & methodology: The anionic CD44-targeting chon- droitin sulfate and cationic low density lipoprotein (LDL)-targeting lactoferrin (LF) were sequentially as- sembled onto the surface of the positively charged oily core. As an imaging probe, highly fuorescent mercaptopropionic acid-capped cadmium telluride QDs were coupled to LF. Results: In vitro, fuorescence of QDs was quenched (OFF state) due to combined electron/energy transfer-mediated processes involving LF. After intracellular uptake of NCs, fuorescence was restored (ON state), thus enabled tracing their in- ternalization. The NCs demonstrated enhanced cytotoxicity against breast cancer cells as well as superior in vivo antitumor effcacy. Conclusion: We propose these multifunctional nanotheranostics for imaging and targeted therapy of breast cancer. First draft submitted: 11 June 2018; Accepted for publication: 09 August 2018; Published online: 19 October 2018 Keywords: cancer imaging • cancer theranostics • celecoxib • chondroitin sulfate • honokiol • lactoferrin-QDs con- jugate • self-targeted nanocapsules Breast cancer is considered to be the most widely diagnosed cancer type excluding skin cancer types [1]. COX with its two forms (COX-1 and COX-2) is the enzyme responsible for prostaglandins formation from arachidonic acid. However, COX-2 is overexpressed in various tumors with a greater contribution to cancer development. It was reported to increase production of prostaglandins, activate procarcinogens into carcinogens, inhibit apoptosis, promote angiogenesis and increase tumor cell invasiveness [2]. Celecoxib (CXB) is a specific COX-2 inhibitor with antitumor efficacy that is manifested by reduction in proliferation of tumor cells due to increase in B- catenin oncoprotein degradation and increase apoptosis effect [3]. However, it displays low aqueous solubility and serious oral side effects as gastrointestinal toxicity, ulcer formation due to production inhibition of prostaglandin, as well as cardiovascular problems [4]. To overcome these limitations, many drug-delivery systems were used as self microemulsifying systems, liposomes and nanocapsules (NCs) [5,6]. Recently, multireservoir protamine NCs have been developed in our laboratory for combined delivery of letrozole as an aromatase inhibitor and CXB as a selective COX-2 inhibitor. CXB was found to synergistically enhance letrozole efficacy against cancer by suppressing aromatase expression, activating apoptosis and inhibiting angiogenesis [6,7]. Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889 10.2217/nnm-2018-0196 C  2018 Future Medicine Ltd