Self-Assembled Biodegradable Protein–Polymer Vesicle as a Tumor-Targeted Nanocarrier

Abstract

Self-assembled nanostructures based on amphiphilic protein-polymer conjugates have shown great advantages in the field of nanomedicine such as inherent biocompatibility with biosystems because of their excellent performance. Herein, a novel biodegradable protein-polymer conjugate was prepared by covalently linking the tailor-made hydrophobic maleimide-functionalized poly(ε-caprolactone) (PCL) to hydrophilic bovine serum albumin (BSA) via the maleimide-sulfhydryl coupling reaction. This protein-based conjugate with a biodegradable polyester was reported for the first time, and the obtained biohybrid displayed well-defined structure, excellent biocompatibility and low cytotoxicity, and self-assembly behaviors similar to those of the traditional amphiphilic small molecules and block copolymers. The amphiphilic BSA-PCL conjugate can self-assemble into a nanosized vesicle with a negative surface charge. Furthermore, the self-assembled vesicle based on the BSA-PCL conjugate was functionalized via linking targeting ligand cetuximab to its surface to enhance cell uptake, and the doxorubicin (DOX)-encapsulated cetuximab-functionalized vesicle exhibited enhanced antitumor activity compared with that of free DOX in vitro. These results indicate that the biodegradable protein-polymer conjugate based on BSA and PCL had great potential as a drug delivery vehicle for cancer therapy.

Facile Construction of Near Infrared Fluorescence Nanoprobe with Amphiphilic Protein-Polymer Bioconjugate for Targeted Cell Imaging

“…The coupling of the maleimide-functionalized PCL to the reduced BSA was performed in a DMF/water mixture (10/90, v/v) according to our previous reported method. 23 Briefly, maleimide-functionalized PCL-(Mal-PCL) was first synthesized by ring-opening polymerization (ROP) of ε-caprolactone in the presence of N-(2-hydroxyethyl)-maleimide as an initiator and stannous octoate as a catalyst, and the molecular weight of it, as determined by GPC, was 3216 Da. The DMF solution of Mal-PCL (0.15 mM) was added to the reduced BSA in water (0.015 mM, 100 mM phosphate buffer, pH = 6.8, 2 mM EDTA, 150 mM NaCl).…”

Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression

“…In recent studies, a similar treatment with the antihuman EGFR antibody C225 showed no cytotoxicity using the MTT assay (Mamot et al 2003). EGFR-BSA-PCL and BSA-PCL also showed no cytotoxicity using the MTT assay (Liu et al 2014). Furthermore, nanoparticles containing C225-Fab, but lacking an encapsulated drug, similarly showed no cytotoxicity under these MTT assay conditions (Mamot et al 2003).…”

“…The amphiphilic BSA-PCL conjugate was synthesized as previously described (Liu et al 2014), and the nanosized self-assembled amphiphilic BSA-PCL conjugate was obtained via the emulsion-solvent evaporation method (Du et al 2013). Briefly, 4 mg of BSA-PCL conjugate was dissolved in 4 mL of phosphate buffer (PB, 0.1 M, pH 7.4) at room temperature and activated with N-(3-dimethyl amino propyl)-3-2 ethyl carbon imine hydrochloride (EDC) and N-hydroxy succinimide (NHS) for 15 min, to which 5 mg/ mL cetuximab antibodies were added (100 μg cetuximab antibodies per 1 mg BSA-PCL) at 4 °C overnight.…”

“…The obtained PB solutions of the self-assemblies of the BSA-PCL conjugate and the cetuximab-decorated BSA-PCL conjugate EGFR-BSA-PCL were stored at 4 °C. The EGFR-BSA-PCL and BSA-PCL conjugates were synthesized by Liu Zhongyun, Ph.D., and Professor Chang Jin from TianJin University, Department of Polymer Materials Science and Engineering (Liu et al 2014). Nanoparticles were dissolved in 10 % Triton X-100 for measurement of BSA and cetuximab antibody content by high-performance liquid chromatography (HPLC) (Chen et al 2015).…”

Biodegradable double nanocapsule as a novel multifunctional carrier for drug delivery and cell imaging

“…Also, previous studies reported that cells uptake the albumin nanoparticles by receptor-mediated endocytosis, since there exists cancer-specific albumin-binding protein on the tumor cell lines, evidenced by competition studies of free albumin and co-precipitation results of albumin receptors. 41,42 These studies implied that albumin nanocarriers might be used for specific tumor cell imaging in vitro and in vivo.…”