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Nano–Cell Interactions of Non-Cationic Bionanomaterials
journal contribution
posted on 2019-05-06, 00:00 authored by Lok Wai
Cola Ho, Yao Liu, Ruifang Han, Qianqian Bai, Chung Hang Jonathan ChoiConspectusAdvances in nanotechnology have empowered the design of bionanomaterials
by assembling different types of natural biomolecules (e.g., nucleic
acids, proteins, and lipids) as building blocks into nanoparticles
(NPs) of 1–100 nm in diameter. Such bionanomaterials form the
basis of useful nanomedicine applications, such as targeted delivery,
gene regulation, molecular diagnostics, and immunomodulation. To achieve
optimal performance in these applications, it is imperative that the
NPs be delivered effectively to the organs, tissues, and cells of
interest. A rational approach to facilitating the delivery of NPs
is to develop a detailed and comprehensive understanding in their
fundamental interactions with the biological system (or nano–bio
interactions). Rigorous nano–bio research can provide mechanistic
insights for circumventing the bottlenecks associated with inefficient
and nonspecific delivery of NPs, catalyzing the clinical translation
of nanomedicines.Cationic liposomes and lipid NPs are conventional
carriers of therapeutic
cargoes into cells due to their high ability to penetrate the cell
membrane, a barrier comprised by an anionic phospholipid bilayer.
Yet, cationic NPs tend to cause cytotoxicity and immune responses
that may hamper their clinical translation. Contrary to cationic NPs,
non-cationic NPs (be they near-neutral or anionic in surface charge)
generally exhibit higher biocompatibility but enter mammalian cells
in much less pronounced amounts. Intriguingly, some types of non-cationic
NPs exhibit high biocompatibility and cellular uptake properties,
all attractive features for intracellular delivery.In this
Account, we present our studies of the interactions of
non-cationic bionanomaterials with cells (or nano–cell interactions).
To start with, we introduce the use of near-neutral poly(ethylene
glycol)-coated NPs for probing the roles of two rarely explored physicochemical
parameters on cellular uptake, namely, extracellular compression and
alkylation. We next present the nano–cell interactions of two
representative types of anionic bionanomaterials that effectively
enter mammalian cells and have found widespread applications in the
past decade, including DNA-coated NPs and polydopamine (PDA)-coated
NPs. In our cell-based studies, we dissect the route of intracellular
trafficking, pathway proteins that dictate cellular uptake, and trafficking
of NPs. We further touch on our recent quantitative analysis of the
cellular-level distribution of NPs in various organs and tissues of
diseased animal models. Our results offer important design rules of
NPs for achieving effective intracellular delivery and may even guide
us to explore nanomedicine applications that we did not conceive before,
such as using DNA-coated NPs for targeting atherosclerotic plaques
and PDA-coated plasmonic nanoworms for photothermal killing of cancer
cells. We conclude with our perspectives in elucidating nano–bio
interactions via a reductionist approach, calling for closer attention
to the role of functional groups and more refined studies on the organelle-level
distribution of NPs and the genetic basis of in vivo distribution
of NPs.