5 research outputs found
Ultrasensitive pH Triggered Charge/Size Dual-Rebound Gene Delivery System
A facile
strategy is developed to construct an ultrasensitive pH
triggered charge/size dual-rebound gene delivery system for efficient
tumor treatment. The therapeutic gene is complexed by polyethylenimine
(PEI) and poly-l-glutamate (PLG), further in situ tightened
by aldehyde modified polyethylene glycol (PEG) via Schiff base reaction.
The generated Schiff base bonds are stable in neutral pH but cleavable
in tumor extracellular pH. This gene delivery system possesses following
favorable properties: (1) the tunable gene delivery system is constructed
by chemical bench-free “green” and fast process which
is favored by clinician, (2) PEG cross-linking shields the surface
positive charges and tightens the complex particles, leading to decreased
cytotoxicity, improved stability, and prolonged circulation, (3) PEG
shielding can be rapidly peeled off by acidic pH as soon as arriving
tumors, (4) dual charge/size ultrasensitively rebounding to higher
positive potential and bigger size enhances tumor cell uptake efficiency.
A series of experiments both in vitro and in vivo are carried out
to investigate this gene delivery system in detail. An antiangiogenesis
therapeutic gene is carried for the treatment of CT26 tumors in mice,
achieving superior antitumor efficacy which is well proved by sufficient
biological evidence. The system has great potentials for cancer therapy
in the future
Additional file 1 of Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy
Additional file 1: Figure S1. Particle size and PDI of PKF-Ce6 blank micelles. Figure S2. Pharmacokinetics profiles of Ce6 after administration in mice (n=3). Figure S3. H&E staining of major organs (heart, liver, spleen, lung and kidneys) collected from one mouse after treatment, scale bar is 20 ÎĽm. Table S1. Particle size of PCD micelles with different ratio of Ce6 to DCPT. Table S2. Pharmacokinetic parameters of DCPT, PCD and PPCD after administration in mice (n=3). Table S3. Pharmacokinetic parameters of Ce6, PCD and PPCD after administration in mice (n=3)
A pH-Responsive Detachable PEG Shielding Strategy for Gene Delivery System in Cancer Therapy
In
this study, a pH-responsive detachable polyethylene glycol (PEG)
shielding strategy was designed for gene delivery in cancer therapy.
Polyethylenimine/DNA complex (PEI/DNA) was in situ shielded by aldehyde
group-modified PEG derivatives. The aldehyde groups of PEG could react
with the amino groups of PEI by Schiff base reaction. The Schiff base
bond was stable in neutral pH but labile in slightly acidic pH, which
made the PEG sheddable in tumors. PEG-coated nanoparticles (NPs) had
distinct advantages compared to their mPEG counterpart, possessing
decreased zeta potential, more compressed size, and enhanced stability.
PEG/PEI/DNA NPs showed not only high tumor cell uptake and transfection
efficiency in vitro but also efficient accumulation and gene expression
in solid tumors in vivo. This pH-responsive detachable PEG shielding
system has the potential to be applied to other polycationic nanoparticles
that contain amino groups on their surfaces, which will have broad
prospects in cancer therapy
pH Triggered Size Increasing Gene Carrier for Efficient Tumor Accumulation and Excellent Antitumor Effect
High
efficiency and serum resistant capacity are important for gene carrier
in vivo usage. In this study, transfection efficiency and cell toxicity
of polyethylenimine (PEI) (branched, Mw = 25K) was remarkably improved,
when mixed with polyanion (polyethylene glycol-polyglutamic acid (PEG–PLG)
or polyglutamic acid (PLG)). Different composite orders of PEI, polyanion,
and gene, for example, PEI is first complexed with DNA, and then with
polyanion, or PEI is first complexed with polyanion, and then with
DNA, were studied. Results showed that only the polyanion/PEI complexes
exhibited additional properties, such as decreased pH, resulting in
increased particle size, as well as enhanced serum resistance capability
and improved tumor accumulation. The prepared gene carrier showed
excellent antitumor effect, with no damage on major organs, which
is suitable for in vivo gene antitumor therapy
Gold-Nanorods-Based Gene Carriers with the Capability of Photoacoustic Imaging and Photothermal Therapy
Multifunctional
nanoparticles with high gene transfection activity, low cytotoxicity,
photoacoustic imaging ability, and photothermal therapeutic properties
were prepared by conjugating low-molecular-weight polyethylenimine
onto the surfaces of gold nanorods through the formation of stable
S–Au bonded conjugates. Results revealed that the gene transfection
efficiency of the prepared polyethylenimine-modified gold nanorods
(GNRs-PEI1.8k) was higher and their cytotoxicity was less than those
of the commercial reagent PEI25k. GNRs-PEI1.8k could also be potentially
used as a photoacoustic and photothermal reagent to evaluate the pharmacokinetics,
biodistribution, and antitumor effects of gene/drug nanoparticles.
Therefore, GNRs-PEI1.8k can be considered a promising candidate for
the clinical diagnosis and treatment of tumors