pH-sensitive Au–BSA–DOX–FA nanocomposites for combined CT imaging and targeted drug delivery

Abstract

Albumin-based nanoparticles (NPs) as a drug delivery system have attracted much attention owing to their nontoxicity, non-immunogenicity, great stability and ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA) was utilized as a template to prepare Au–BSA core/shell NPs. The outer layer BSA was subsequently conjugated with cis -aconityl doxorubicin (DOX) and folic acid (FA) to create Au–BSA–DOX–FA nanocomposites. A list of characterizations was undertaken to identify the successful conjugation of drug molecules and targeted agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8) assay indicated that Au–BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells in the concentration range of 0–100 μg/mL, which can therefore be used as a safe drug delivery carrier. Furthermore, compared with free DOX, Au–BSA–DOX–FA nanocomposites exhibited a pH-sensitive drug release ability and superior antitumor activity in a drug concentration-dependent manner. In vivo computed tomography (CT) imaging experiments showed that Au–BSA–DOX–FA nanocomposites could be used as an efficient and durable CT contrast agent for targeted CT imaging of the folate receptor (FR) overexpressed in cancer tissues. In vivo antitumor experiments demonstrated that Au–BSA–DOX–FA nanocomposites have selective antitumor activity effects on FR-overexpressing tumors and no adverse effects on normal tissues and organs. In conclusion, the Au–BSA–DOX–FA nanocomposite exhibits selective targeting activity, X-ray attenuation activity and pH-sensitive drug release activity. Therefore, it can enhance CT imaging and improve the targeting therapeutic efficacy of FR-overexpressing gastric cancers. Our findings suggest that Au–BSA–DOX–FA nanocomposite is a novel drug delivery carrier and a promising candidate for cancer theranostic applications.

<p>Targeted Therapy for Hepatocellular Carcinoma: Co-Delivery of Sorafenib and Curcumin Using Lactosylated pH-Responsive Nanoparticles</p>

“…The drug release from nanoparticles was investigated by quantifying the drug amounts in the presence of different pH media. 54 Compared with less than 60% of drug release obtained at pH 7.4, cumulative release of SFN and CCM from nanoparticles at pH 5.5 was over 80%, indicating comparative stability in neutral conditions. 55 The release rate was dramatically improved due to hydrolysis of hydrazone, accelerating the drug release at decreasing pH values, consistent with large numbers of recent studies in pH-responsive drug delivery system.…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…Recently, albumin coated on gold nanoparticles modified with FA- for FR-targeted drug delivery was combined with the chemotherapeutic DOX and computed tomography (CT) imaging. The Au-BSA-DOX-FA nanocomposites exhibited antitumor activity specifically on FR-overexpressing tumors, and no toxicity was observed in normal healthy tissues (Huang et al, 2017). …”

Biomedical applications of bismuth oxide based nanocomposite: computed tomography and anticancer drug loading

“…Bovine serum albumin (BSA) is a protein which is usually used as a template for preparation of nanocomposites. Because of high number of binding sites, BSA has a high potential to bind many drug moieties comparing to other substrates [20]. In addition, BSA has excellent biocompatibility, and good water solubility and colloidal stability [21].BSA commonly uses for the surface modification of nanoparticles [22].…”