Single-component Polymer Nanocapsules for Drug Delivery Application

The design of delivery vehicles for transporting anticancer drugs to tumor sites has gained traction during the past few decades. Utilizing polymer-based materials has played an important role in the development of such systems, largely because of the ability to prepare polymers with tailored properties, including biocompatibility, size, structure, and functionality. Several polymer-based vehicles have been reported, including polymer particles, polymer-based micelles, polymer-drug conjugates, and polymer nanocapsules. These systems can facilitate higher payloads, prolong the circulation time of the drugs, improve drug targeting and solubility, and provide controlled-release of the therapeutics into the blood stream or the targeted tumor tissues. Among these, the polymer capsules are particularly attractive candidates for drug delivery applications. ‘‘Layer-by-layer (LbL) assembly processes have been widely used by our group and others to prepare polymer capsules with well-defined chemical and structural properties. In LbL assembly, a nonporous sacrificial colloidal template is generally used to sequentially deposit multiple polymer layers one after another, followed by removal of the core, leading to well-defined polymer capsules with nanometer-thick walls’’, Prof. Frank Caruso, Director of the Centre for Nanoscience and Nanotechnology at the University of Melbourne, Australia, explains to Nanospotlight. ‘‘Multiple assembly steps required in the LbL assembly often require the use of more than one polymer and can make the process relatively intensive and timeconsuming, particularly for the synthesis of thick walled polymer capsules.’’ To overcome these limitations, Prof. Caruso’s team used a novel silica particle template with a solid core and mesoporous shell (SC/MS) for polymer nanocapsules synthesis. Prof. Caruso further explains to Nanospotlight: ‘‘The use of SC/MS template allows a ‘single polymer’ to be infiltrated in the mesoporous shells of SC/MS particles in a ‘single macromolecular assembly step’ by solution adsorption, followed by cross-linking of the macromolecules in the mesoporous silica shells, and subsequent removal of the SC/MS templates, thus leading to monodispersed, single-component and thick-walled polymer nanocapsules (see Scheme 1).’’ ‘‘This approach offers a number of advantages over the conventional LbL technique to prepare capsules. Firstly, uniform nanocapsules of various macromolecules are obtained by a single macromolecular assembly step of a single macromolecule type, eliminating the need for multiple polymers and/or multiple polymer adsorption steps. Secondly, the nanocapsules derived from the SC/MS templates have porous walls that are significantly thicker than those prepared by LbL assembly (e.g., more than an order of magnitude for a single adsorption step), thus offering a simple approach to regulate the physical properties (e.g., structure, permeability, payloads) of the nanocapsules.’’ The SC/MS particles can be prepared with different particle size, shell thickness, and solid core composition (e.g., silica, gold and Fe3O4 nanoparticles). The size and thickness of the nanocapsules can be controlled by choosing the appropriate size SC/MS template and type and molecular weight of the polymers. For instance, the thickness of the capsule shells increases as the molecular weight of the PAH decreases because of more efficient adsorption of smaller species of PAH in the mesoporous shells of SC/MS templates (*45 nm and *16 nm thick capsules with a diameter of *400 nm size were obtained for PAH of 5 and 70 kDa, respectively). Furthermore, the macromolecules assembled in the capsules can be stabilized via engineered cleavable covalent linker (e.g.,