Development of Polydopamine Nanotubes into a Multi-Functional Drug Delivery System

Abstract

In this study, a template-assisted method for the synthesis of polydopamine nanotubes is developed. By altering the amount ratio between dopamine and template, a robust tubular structure is obtained. This unique process allows modification of the outer and inner layers of the nanotube in separate steps. The outer layer of the nanotubes is coated with polyethylene glycol to enhance its biocompatibility. Then the inner layer is modified with thermo-sensitive poly(N-isopropylacrylamide) to increase the nanostructure’s thermal responsiveness. The modified nanotubes show better stability in an aqueous solution than the pristine nanotubes. Moreover, the photothermal effect of polydopamine allows the remote control of poly(N-isopropylacrylamide), which presents a hydrated or dehydrated state under different temperatures. Furthermore, the abundant catechol groups present as the reductive sites to immobilize the Fe3O4 magnetic nanoparticles, which endows magnetic response to the nanotubes. To investigate the controlled release of nanotubes' capability to payloads, doxorubicin, a cationic small molecular drug, is used as a payload model. The release rate in different pH, magnetic field, and a near-infrared laser is tested. As a result, a multi-linear regression model is established to describe the impacts of various stimuli on the doxorubicin release rate from the nanotube. Besides the nanotube, synthesis of hollow polydopamine bowl-shaped nanocapsules (nanobowls), as small as 80 nm in diameter, via a one-pot template-free rapid method is developed in this study. The addition of dopamine to a solution of 0.606 mg/ml Tris(hydroxymethyl) aminomethane in an ethanol/water mixed solvent results in hollow spherical formation nanocapsules within two hours. At longer reaction times, the formation of conventional solid nanospheres dominates the reaction. The nanocapsules’ wall thickness was increased as the dopamine concentration in the reaction medium increased and sufficient oxygen supported. Under dehydrated status, the nanocapsules with thin wall thickness and prepared with deficient oxygen were prone to collapse. Moreover, the degree of collapse of individual nanoparticles changes from complete to partial to no collapse as the wall thickness increased. Varying the ethanol content affects the nanocapsules’ cavity size and overall dimension but does not result in a noticeable change in their wall thickness. The largest cavity and dimension appear with 20 vol.% ethanol contained in the reaction medium. The formation mechanism of the hollow nanocapsule structure related to the lower solubility of dopamine in alcohol solvent is then provided.