ORIGINAL PAPER Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery Massoumeh Bagheri & Shaghayegh Shateri & Hassan Niknejad & Ali Akbar Entezami Received: 16 April 2014 /Accepted: 9 September 2014 # Springer Science+Business Media Dordrecht 2014 Abstract In this article, we report the synthesis of a novel amphiphilic hydroxypropyl cellulose-based polymer (HPC- PEG-Chol) that contained poly (ethylene glycol) and cholesterol-containing moieties with specific degrees of sub- stitution. The resulting polymer was subsequently converted to a biotin conjugate (HPC-PEG-Chol-biotin), to develop a new potential cancer-targeted drug delivery system. The bio- tin conjugate was used to prepare micelles via the dialysis method. The polymeric micelles in aqueous solution present- ed a lower critical solution temperature (LCST) of 39.8 o C. The critical micelle concentration (CMC) values of the poly- meric micelles at 25 and 45 °C were evaluated to be about 0.32 and 0. 25 g/L, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses of the micelles revealed the spherical shapes of the micelles, with 84 nm mean diameters that increased with the increase of the temperature above LCST. The hydrophobic anticancer drug paclitaxel (PTX) was loaded in the micelles and the in vitro release behaviors of PTX were investigated at differ- ent temperatures. The release profile of PTX from the poly- meric micelles revealed a thermosensitivity, since its release rate was higher at 41 °C than at 37 °C. Fluorescent microsco- py analyses confirm that the PTX-loaded HPC-PEG-Chol- biotin is superior in cellular uptake, with very strong adsorp- tion to both HeLa and MDA-MB-231 cancer cell lines. MTT assay in normal cells indicated that HPC-PEG-Chol-biotin micelles have great potential to be safely used in tumor- targeting chemotherapy. Keywords Cancer-targeted drug delivery . Paclitaxel . Tumor-targeted chemotherapy . Polymeric micelles Introduction Due to the specific properties that are ascribed to the unique core–shell architecture, polymeric micelles have emerged as potential carriers in the various fields of drug delivery, with the characters of solubilization, low toxicity, long-circulation and tumor localization [1, 2]. Recently, they have been recog- nized as one of the most promising formulations for anti- tumor drug delivery, as they successfully increase the solubil- ity of many poorly water-soluble drugs [3]. Polymeric mi- celles are self-assembled by amphipathic block or graft copol- ymers [4]. Due to their excellent physicochemical properties, in recent years, much attention has been paid to natural polysaccharide- based amphiphilic graft copolymers as potential vehicles for anti-cancer drugs [5]. Among polysaccharides, hyaluronic acid, chitosan and dextran have been largely investigated for drug bioconjugation, as the therapeutic properties of antican- cer drugs can be combined with the biological properties of these polymers [6]. Above the critical micelle concentration (CMC), these polymers may associate into a core–shell Electronic supplementary material The online version of this article (doi:10.1007/s10965-014-0567-4) contains supplementary material, which is available to authorized users. M. Bagheri (*) : S. Shateri Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University, P.O. Box: 53714-161, 5375171379 Tabriz, Iran e-mail: massoumehbagheri@yahoo.com H. Niknejad Department of Tissue Engineering, Scholl of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran H. Niknejad Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran A. A. Entezami Polymer Laboratory, Organic Chemistry department, Chemistry Faculty, Tabriz University, Tabriz, Iran J Polym Res (2014) 21:567 DOI 10.1007/s10965-014-0567-4