No abstract

Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for an efficient cellular uptake through the plasma membrane, and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. The cellular internalization routes have a determining effect on the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine, and presents an account of ligand targeted nanoparticles for receptor mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has even resulted in a remarkable development towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial cellular barrier. A detailed overview of the recent developments towards subcellular targeting that is emerging as a platform for the next generation organelle specific nanomedicines is also provided. Each section of the review includes prospect, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.

In this work we describe for the first time the integration of "smart" polymer brushes into single conical nanopores to obtain a new highly functional signal-responsive chemical nanodevice. The responsive brushes were constituted of zwitterionic monomers whose charge is regulated via pH changes in the environmental conditions. The pH-dependent chemical equilibrium of the monomer units provides a fine-tuning of the ionic transport though the nanopore by simply presetting the pH of the electrolyte solution. Our results demonstrate that this strategy enables a higher degree of control over the rectification properties when compared to the nanochannels modified with charged monolayer assemblies. We envision that these results will create completely new avenues to build-up "smart" nanodevices using responsive polymer brushes integrated into single conical nanopores.