Enzyme-catalyzed self-propelling particles : applications for drug delivery to solid tumors

Abstract

We report the design and synthesis of silica Janus motors via the Pickering emulsion method, using a naturally occurring enzyme, catalase, which catalyzes the decomposition of hydrogen peroxide into water and oxygen. Enzymes offer many benefits over conventional metal catalysts which are commonly used in Janus motors. They typically exhibit higher catalytic efficiencies which can also be tuned by adjusting environmental conditions such as pH, temperature, chemical activators/inhibitors and so on. Particle tracking experiments on the particles allowed us to probe the mechanisms by which these particles achieve propulsion. Since the eventual goal of this work is to test these particles as drug delivery agents, an in vitro 3D tumor spheroid model of breast cancer has also been developed using a metastatic breast cancer cell line (MDA-MB-231) and Collagen Type I as the extra-cellular matrix. This model was used to investigate the expression of an important cell surface biomarker, the transferrin receptor (TfR), which has been used previously to design particles for targeted therapy to tumors. The work presented here lays the foundation for the use of Janus motors as drug carriers which incorporate both an active enzyme as well as a targeting ligand such as Transferrin that can potentially overcome the transport barriers faced by conventional systems, and lead to improved therapies.

Cancer is one of the oldest diseases known to mankind, and remains one of the most complex ailments to diagnose, treat and manage. Considerable scientific research has been conducted to understand the mechanisms that govern cancer and to discover therapeutics, and yet this class of diseases still accounts for a lion's share of the global health burden. An emerging consensus over the past decade has been the importance of the 'tumor microenvironment' in the progression of the disease. The many transport barriers imposed by the microenvironment renders even potent drugs inefficient and makes them poor therapeutic candidates. In this context, nanotechnology has emerged as a powerful resource, since it operates at length scales commonly found in biology, and also provides the opportunity to engineer nanoparticle-based drug carrier systems which incorporate the desirable traits of an efficient therapeutic.

The work presented here is based on the idea that nano-scale objects can be designed to use the tumor microenvironment to improve their transport and distribution. Janus Particles are a special class of nanoparticles that exhibit some form of physical and/or chemical asymmetry on their surface. Of special interest is a class of Janus particles called `Janus motors', which are designed specifically to use this asymmetry to convert chemical energy to mechanical energy and achieve `self-propulsive' motion.