4 research outputs found
Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles
Biodegradable and biocompatible polymeric nanoparticles
(NPs) stand
out as a key tool for improving drug bioavailability, reducing the
inherent toxicity, and targeting the intended site. Most importantly,
the ease of polymer synthesis and its derivatization to add functional
properties makes them potentially ideal to fulfill the requirements
for intended therapeutic applications. Among many polymers, US FDA-approved
poly(l-lactic-co-glycolic) acid (PLGA) is
a widely used biocompatible and biodegradable co-polymer in drug delivery
and in implantable biomaterials. While many studies have been conducted
using PLGA NPs as a drug delivery system, less attention has been
given to understanding the effect of NP weight on cellular behaviors
such as uptake. Here we discuss the synthesis of PLGA NPs with varying
NP weights and their colloidal and biological properties. Following
nanoprecipitation, we have synthesized PLGA NP sizes ranging from
60 to 100 nm by varying the initial PLGA feed in the system. These
NPs were found to be stable for a prolonged period in colloidal conditions.
We further studied cellular uptake and found that these NPs are cytocompatible;
however, they are differentially uptaken by cancer and immune cells,
which are greatly influenced by NPs’ weight. The drug delivery
potential of these nanoparticles (NPs) was assessed using doxorubicin
(DOX) as a model drug, loaded into the NP core at a concentration
of 7.0 ± 0.5 wt % to study its therapeutic effects. The results
showed that both concentration and treatment time are crucial factors
for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting
a higher potency at lower concentrations. The observations revealed
that DOX-NPs exhibited a higher cellular uptake of DOX compared to
the free-DOX treatment group. This will allow us to reduce the recommended
dose to achieve the desired effect, which otherwise required a large
dose when treated with free DOX. Considering the significance of PLGA-based
nanoparticle drug delivery systems, we anticipate that this study
will contribute to the establishment of design considerations and
guidelines for the therapeutic applications of nanoparticles
Multiparametric Magneto-fluorescent Nanosensors for the Ultrasensitive Detection of Escherichia coli O157:H7
Enterohemorrhagic Escherichia coli O157:H7 presents a serious threat
to human health and sanitation and is a leading cause in many food-
and waterborne ailments. While conventional bacterial detection methods
such as PCR, fluorescent immunoassays and ELISA exhibit high sensitivity
and specificity, they are relatively laborious and require sophisticated
instruments. In addition, these methods often demand extensive sample
preparation and have lengthy readout times. We propose a simpler and
more sensitive diagnostic technique featuring multiparametric magneto-fluorescent
nanosensors (MFnS). Through a combination of magnetic relaxation and
fluorescence measurements, our nanosensors are able to detect bacterial
contamination with concentrations as little as 1 colony-forming unit
(CFU). The magnetic relaxation property of our MFnS allow for sensitive
screening at low target CFU, which is complemented by fluorescence
measurements of higher CFU samples. Together, these qualities allow
for the detection and quantification of broad-spectrum contaminations
in samples ranging from aquatic reservoirs to commercially produced
food
Combination Therapy of NSCLC Using Hsp90 Inhibitor and Doxorubicin Carrying Functional Nanoceria
K-RAS driven non-small-cell lung
cancer (NSCLC) represents a major
cause of death among smokers. Recently, nanotechnology has introduced
novel avenues for the diagnosis and personalized treatment options
for cancer. Herein, we report a novel, multifunctional nanoceria platform
loaded with a unique combination of two therapeutic drugs, doxorubicin
(Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and
effective treatment of NSCLC. We hypothesize that the use of ganetespib
synergizes and accelerates the therapeutic efficacy of Doxo via ROS
production, while minimizing the potential cardiotoxicity of doxorubicin
drug. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles (PNC)
were fabricated for the targeted combination therapy of lung cancers.
Using “click” chemistry, the surface carboxylic acid
groups of nanoceria were decorated with folic acid to target folate-receptor-overexpressing
NSCLC. As a result of combination therapy, results showed more than
80% of NSCLC death within 48 h of incubation. These synergistic therapeutic
effects were assessed via enhanced ROS, cytotoxicity, apoptosis, and
migration assays. Overall, these results indicated that the targeted
codelivery of Doxo and GT using nanoceria may offer an alternative
combination therapy option for the treatment of undruggable NSCLC
Design and Synthesis of New Sulfur-Containing Hyperbranched Polymer and Theranostic Nanomaterials for Bimodal Imaging and Treatment of Cancer
In this study, we
have synthesized a new hyperbranched polyester
polymer containing sulfur-pendants (HBPE-S) in the branching points.
This HBPE-S polymer is composed of spherical shaped, aliphatic three-dimensional
architecture with carboxylic acid groups on the surface. The presence
of sulfur pendants in the polymeric cavities demonstrated an important
role in the effective encapsulation of Bi-DOTA complexes ([Bi] = 5.21
μM), when compared to the previously reported polymer without
sulfur pendants (HBPE, [Bi] = 1.07 × 10<sup>–3</sup> μM).
Higher X-ray blocking capability and excellent X-ray contrast images
were obtained from Bi-DOTA encapsulating HBPE-S polymeric nanoparticles
when compared with that of HBPE nanoparticles. In addition, the HBPE-S
polymer’s spherical structure with amphiphilic cavities allow
for the successful encapsulation of antitumor drugs and optical dyes,
indicating suitable for delivery of wide-range of theranostic agents
for cancer diagnosis and treatment. Therapeutic drug taxol encapsulating,
folic acid decorated HBPE-S-Fol nanoparticles showed more than 80%
of lung carcinoma cell death within 24 h of incubation. Cell viability
and microscopic experiments also confirmed for the targeted delivery,
thereby minimizing toxicity to healthy tissues. Taken together, new
HBPE-S polymer and multimodal theranostic nanoplatforms were synthesized
with enhanced X-ray blocking capability for the effective cancer targeting
and treatment monitoring