Global Journal of Nanomedicine-Juniper Publishers
Abstract
Engineering organic-inorganic nanoparticles play the
greatest advantages in regulating efficacy and safety when targeted
delivery of the small interference RNA (siRNA). This opinion summarizes
the current achievements and looks to the future in this area.
Keywords: siRNA therapeutics; Hybrid nanoparticles; Delivery; Efficacy; Safety
Introduction
Comparing with the traditional treatment modalities,
small interference RNA (siRNA) has immense potential for the treatment
of various human diseases including cancer, since Fire and co-workers
discovered the siRNA in 1998 [1]. Despite the great versatility of RNA
interference (RNAi) technology which could down-regulate any protein in
targeted cells and tissues, many physiological and biological obstacles
still stand in the way of successful, safety and efficient delivery in
application for clinical. The major challenge indeed for RNAi-based
therapy is the development of delivery system [2]. Up to now, a great
number of systems were reported for delivery siRNA including the
non-virus-based platforms [3]. According resurgence in clinical trials
using RNAi occurred in 2012, more than 20 RNAi-based therapeutic cases
are currently in clinical trials, and several of these are Phase III
trials [4].
These encourage us to indicate the advantages of such
platforms, leading to pave the way for the next generation of the siRNA
therapeutics. Particularly, an excited news released from the U.S. Food
and Drug Administration (FDA) has approved the first siRNA therapeutics
for the treatment of peripheral never disease (polyneuropathy) in the
20th anniversary of siRNA Discovery. This great breakthrough encourages
the scientist and industries would be more enthusiastic to develop and
design functional vectors for siRNA therapies to fight the human
diseases. Here, we summarize the advantages of hybrid nanoparticles
including metal/non-metal cores further modification with the organic
shells. Additionally, some typical examples are briefly illustrated here
to provide translational strategies for the siRNA therapeutics in the
near furfure.
Hybrid Nanoparticles in siRNA Therapeutics
Non-viral siRNA delivery hybrid nanoparticles have
shown promise and have travelled to clinical trial applications.
According with the understanding of characterization for the cell types
and targeted tissues to rationally design the efficient vectors for
siRNA therapeutics. Importantly, these functional systems have the
advantages, such as low/non-toxicity, easy fabrication, biodegradation,
biocompatibility, non-immunogenicity, low-price and high efficacy
comparing with the commercial agents [5]. Gold and Quantum dots are the
typically metal-based nanoparticles for the siRNA delivery [6-7].
Nanoparticles with an organic shell embedding a gold core are used for
example in highly efficient, stable, organic light emitting diodes and
organic photovoltaics [8]. For this application the dual purpose of the
nanoparticle is used: gold core offers a plasmatic effect while a
mono-dispersed polystyrene shell gives stability and solvent resistance
[9].
An example of photothermal therapy is given by
proteinases i.e. biological nanoparticles with a gold core and an
organic shell engineered to present specified peptides or proteins [10].
Since biological nanoparticles are synthesized inside living cells,
they present a much lower toxicity compared to synthetic nanoparticles
when use these gold nanoparticles as siRNA delivery systems. Quantum
dots possess particular photochemical properties. For instance, it is
possible to use selective fluorescent to tag proteins as is
traditionally done in classical immunocytochemistry. In addition,
quantum dots present minimal photobleaching and a much higher signal to
noise ratio compared to traditional methods [11]. They possess a broad
absorption spectrum while maintaining a very narrow
emission spectra, allowing multiplexing of many quantum dots
of different colors in the same sample. This is unique and cannot
be achieved using traditional fluorophores. These nanoparticles
could be used in theragnostic siRNA platforms.
The other serial of the hybrid Nano systems is non-metalbased
core with further functional organic shells. Two classical
materials like silica/silicon or carbon-based nanoparticles
widely used for siRNA delivery in vitro and in vivo [12,13]. Precise
nanopore formation and ease of surface modifications are the
main factors that brought interest silicon and silica nanoparticles
to light. Silica nanoparticles have intrinsic biocompatibility,
biodegradability and are efficiently bio-eliminated in vivo.
However, metabolic changes and increased toxicity was observed
especially in vivo due to active silanol groups used for surface
modifications [14]. Some of the modifications applied to silica
nanoparticles involve the synthesis of a cationic polymer layer
or addition of quaternized dendrimers to the surface to permit
electrostatic loading of siRNA, PEG (a protective polymer)
addition to protect nanoparticles and to improve cellular uptake
and delivery of MSNPs-siRNA conjugates [15,16].
Carbon nanotubes possess interesting physical and chemical
properties that allow to easily cross the plasma membrane and
translocate into the cytoplasm of cells. This property is due to
their particular needle shape that exploits the cell’s endocytosisindependent
mechanism without inducing cell death [17]. It
has been shown successful delivery of siRNA using Carbon
Nanotubes by functionalizing the nanotubes with functional
groups. Using this functionalization siRNA was expelled from
the sidewalls of the nanotube to silence telomerase reverse
transcriptase expression inducing tumor growth suppression
[18]. It has also been shown that amino- functionalized
multiwalled carbon nanotubes (f-MWNT) can effectively deliver
in vivo an siRNA sequence while triggering cell apoptosis
resulting in human lung xenograft eradication and prolonged
survival [19]. These nanotube-based siRNA transfer vectors
have shown minimal cytotoxicity and effective delivery and
gene-silencing capabilities.
Conclusion and Outlook
A central message of this opinion is that inorganic-organic
hybrid functional nanoparticles for the siRNA delivery. Under
well understand the properties of such nanoparticles when
they serve as siRNA delivery systems, which successively
addressing each of these barriers, innovative design features can
be rationally incorporated that will create a new generation of
nanotherapeutics, realizing a paradigmatic shift in nanoparticlebased
siRNA delivery.
No comments:
Post a Comment