Amphiphilic Polymer-Mediated Formation of Laponite-Based Nanohybrids with Robust Stability and pH Sensitivity for Anticancer Drug Delivery

Abstract

The development of pH-sensitive drug delivery nanosystems that present a low drug release at the physiological pH and are able to increase the extent of the release at a lower pH value (like those existent in the interstitial space of solid tumors (pH 6.5) and in the intracellular endolysosomal compartments (pH 5.0)) is very important for an efficient and safe cancer therapy. Laponite (LP) is a synthetic silicate nanoparticle with a nanodisk structure (25 nm in diameter and 0.92 nm in thickness) and negative-charged surface, which can be used for the encapsulation of doxorubicin (DOX, a cationic drug) through electrostatic interactions and exhibit good pH sensitivity in drug delivery. However, the colloidal instability of LP still limits its potential clinical applications. In this study, we demonstrate an elegant strategy to develop stable Laponite-based nanohybrids through the functionalization of its surface with an amphiphile PEG-PLA copolymer by a self-assembly process. The hydrophobic block of PEG-PLA acts as an anchor that binds to the surface of drug-loaded LP nanodisks, maintaining the core structure, whereas the hydrophilic PEG part serves as a protective stealth shell that improves the whole stability of the nanohybrids under physiological conditions. The resulting nanocarriers can effectively load the DOX drug (the encapsulation efficiency is 85%), and display a pH-enhanced drug release behavior in a sustained way. In vitro biological evaluation indicated that the DOX-loaded nanocarriers can be effectively internalized by CAL-72 cells (an osteosarcoma cell line), and exhibit a remarkable higher anticancer cytotoxicity than free DOX. The merits of Laponite/PEG-PLA nanohybrids, such as good cytocompatibility, excellent physiological stability, sustained pH-responsive release properties, and improved anticancer activity, make them a promising platform for the delivery of other therapeutic agents beyond DOX.

Two‐Dimensional Nanomaterials for Biomedical Applications: Emerging Trends and Future Prospects

“…One biomedical application to which silicate clays are uniquely suited is hemostasis. Kaolinite has been used to evaluate blood‐clotting disorders since the 1950s, and a zeolite product (QuikClot) is approved for controlling hemorrhages . Recently, silicate clay nanomaterials have been investigated for improving hemostatics .…”

Polymeric Nanohybrids as a New Class of Therapeutic Biotransporters

“…The system showed pH sensitivity and a sustained in vitro release . Using a different approach, Wang et al proposed the design of a nanocomposite formulation based on laponite hybridized with a polyethylene glycol and polylactic acid copolymer (PEG–PLA) as pH‐sensitive carriers of DOX . In this case, a self‐assembling process of the amphiphilic PEG–PLA copolymer on the surface of the laponite was achieved.…”

Influence of laponite on the drug loading and release performance of LbL polyurethane/poly(acrylic acid) multilayers

“…It has pH‐dependent edge surface charges and a large specific surface area as high as 370 m 2 /g, which offer a high loading capacity and pH‐controllable release for a Lap‐based drug delivery system. One research group concentrated on the preparation and application of the Lap‐based drug delivery system in cancer therapy. They found that Lap showed high biocompatibility and enhanced encapsulation efficiency for drugs.…”

“…The loading of the drugs is mainly through the electrostatic interaction between negatively charged polyelectrolytes and the positively charged Lap . To reach a high loading capacity, the pH of the system should be kept above 9.0 to guarantee the negative charges of Lap are big enough . In this work, the fabrication was done at pH 3.2 by alternately depositing water‐soluble weak positive polyelectrolyte polyurethane (PU) and poly(acrylic acid) (PAA)‐Lap nanocomposites on a glass slide.…”