Abstract
pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.
Highlights
We established pH-responsive virus-like nanoparticles (VLNPs) based on hepatitis B core antigen (HBcAg)[9]
Synthesis and characterisation of His-tagged VLNPs conjugated with folic acid (FA-HisHBcAg)
FA was conjugated to the HisHBcAg nanoparticles by using ethyl-3-(3-dimethyl-aminopropyl) -carbodiimide hydrochloride (EDC) and Sulfo-NHS
Summary
We established pH-responsive virus-like nanoparticles (VLNPs) based on hepatitis B core antigen (HBcAg)[9]. We introduce a novel approach to display an anti-cancer drug, DOX, on the HBcAg VLNPs by exploiting the hexahistidine-tag (His-tag) exposed on the surface of the particles (Fig. 1). This approach does not involve a time-consuming drug packaging step and it allows any drug that binds to the His-tags to be displayed on the surface of VLNPs by a simple Add-and-Display step. The His-tagged VLNPs were conjugated with folic acid (FA) using 1-ethyl-3-(3-dimethyl-aminopropyl) -carbodiimide hydrochloride (EDC) and N-hydroxysulfo-succinimide (Sulfo-NHS) These cross-linkers form amide bond between the folate and lysine (Lys) residues at positions 7 and 96 on the HisHBcAg. The FA molecules conjugated to the His-tagged VLNPs would target the particles to cancer cells expressing the folate receptor (FR). This approach would further extend the application of His-tagged molecules in the field of nanomedicine
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
