LAPONITE® nanoplatform functionalized with histidine modified oligomeric hyaluronic acid as an effective vehicle for the anticancer drug methotrexate.

Abstract

The synthetic clay material, LAPONITE® (LAP), having a nanodisk structure together with a negatively charged surface, has been used for effective drug encapsulation by virtue of its interlayer space. In this research effort, the LAP nanodisk was used for the first time to encapsulate the antifolic methotrexate (MTX); the MTX-loaded LAP nanodisks (LAP/MTX) demonstrated a high drug loading efficiency of 80.39%. An efficient and reliable tumor-targeting device that rests on the synthesized oligomeric hyaluronic acid-l-histidine (oHA-His) was then encapsulated in the MTX-loaded LAP disks (forming LAP/MTX/oHA-His nanohybrids). The drug released from the LAP/MTX/oHA-His nanohybrids was pH-dependent and matched the first-order kinetics that describes the diffusion mechanism. In vitro biological evaluation manifested that the MTX-loaded LAP nanocarriers, particularly the LAP/MTX/oHA-His nanohybrids that have targetability and lysosomal antineoplastic activity, can be effectively internalized by the MCF-7 cell line, and can exhibit a more prominent anticancer cytotoxicity than free MTX. In vivo studies with mice indicated that the LAP/MTX/oHA-His nanohybrids demonstrated much higher antitumor efficiency compared to the LAP/MTX nanohybrids and pure MTX. Taken together, the LAP/oHA-His, CD44 receptor targeting and pH-sensitive multifunctional nanohybrids conferred the MTX with excellent cytocompatibility, dispersion stability, sustained pH-responsive release properties, and improved anticancer activity, and may be further developed as a potential active nanoplatform for various anticancer drugs.