High-efficiency freezing-induced loading of inorganic nanoparticles and proteins into micron- and submicron-sized porous particles

Sergei V German,Polina A Demina,Boris N Khlebtsov,Gleb B Sukhorukov,Denis V Voronin,Vsevolod S Atkin,Daniil N Bratashov,Marina V Novoselova,Bogdan V Parakhonskiy,Dmitry A Gorin

doi:10.1038/s41598-018-35846-x

Abstract

We demonstrate a novel approach to the controlled loading of inorganic nanoparticles and proteins into submicron- and micron-sized porous particles. The approach is based on freezing/thawing cycles, which lead to high loading densities. The process was tested for the inclusion of Au, magnetite nanoparticles, and bovine serum albumin in biocompatible vaterite carriers of micron and submicron sizes. The amounts of loaded nanoparticles or substances were adjusted by the number of freezing/thawing cycles. Our method afforded at least a three times higher loading of magnetite nanoparticles and a four times higher loading of protein for micron vaterite particles, in comparison with conventional methods such as adsorption and coprecipitation. The capsules loaded with magnetite nanoparticles by the freezing-induced loading method moved faster in a magnetic field gradient than did the capsules loaded by adsorption or coprecipitation. Our approach allows the preparation of multicomponent nanocomposite materials with designed properties such as remote control (e.g. via the application of an electromagnetic or acoustic field) and cargo unloading. Such materials could be used as multimodal contrast agents, drug delivery systems, and sensors.

Highlights

Increasing the efficiency of loading of functional nanoparticles or molecular substances into porous particles is a currently central research problem
Most published articles dealing with vaterite particles have reported in vitro studies of the uptake efficiency, toxicity, and the kinetic release profiles of drugs[13,16,17]
Vaterite carriers began to be used in vivo more than eight years ago[19,20,21]. They are used in biomedicine as templates and carriers for drug delivery systems

Summary

Introduction

Increasing the efficiency of loading of functional nanoparticles or molecular substances into porous particles is a currently central research problem. Vaterite particles are used in the preparation of food-friendly polymer additives[24] and in water purification[25] Their transfer from R&D to industrial application has been made difficult by the lack of an efficient loading approach. The freezing/thawing approach has been used widely for many purposes, including the fabrication of lamellar[29] and porous structures, micro- and nanowires, and micro- and nanoparticles[1,30] This approach is based on controlled directional freezing, so that ice crystals grow in a single direction[1]. The ice crystals grow as a lamellar microstructure parallel to the a-direction, forming so-called cold-finger interfaces[31] Until now, this approach has not been used to load inorganic nanoparticles into micron and submicron porous particles. We propose the use of the cold finger approach for the freezing-induced loading (FIL) of inorganic nanoparticles into the porous matrices of vaterite particles

Methods

Findings

Discussion

Conclusion