3 research outputs found
A Combined Approach Employing Chlorotoxin-Nanovectors and Low Dose Radiation To Reach Infiltrating Tumor Niches in Glioblastoma
Glioblastoma multiforme (GBM) is
the most aggressive form of glioma,
with life expectancy of around 2 years after diagnosis, due to recidivism
and to the blood-brain barrier (BBB) limiting the amount of drugs
which reach the residual malignant cells, thus contributing to the
failure of chemotherapies. To bypass the obstacles imposed by the
BBB, we investigated the use of nanotechnologies combined with radiotherapy,
as a potential therapeutic strategy for GBM. We used polyÂ(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles (PNP) conjugated
to chlorotoxin (CTX), a peptide reported to bind selectively to glioma
cells. Silver nanoparticles were entrapped inside the functionalized
nanoparticles (Ag-PNP-CTX), to allow detection and quantification
of the cellular uptake by confocal microscopy, both <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i> experiments
performed with different human glioblastoma cell lines showed higher
cytoplasmic uptake of Ag-PNP-CTX, with respect to nonfunctionalized
nanoparticles. <i>In vivo</i> experiments showed that Ag-NP-CTX
efficiently targets the tumor, but are scarcely effective in crossing
the blood brain barrier in the healthy brain, where dispersed metastatic
cells are present. We show here that single whole brain X-ray irradiation,
performed 20 h before nanoparticle injection, enhances the expression
of the CTX targets, MMP-2 and ClC-3, and, through BBB permeabilization,
potently increases the amount of internalized Ag-PNP-CTX even in dispersed
cells, and generated an efficient antitumor synergistic effect able
to inhibit <i>in vivo</i> tumor growth. Notably, the application
of Ag-PNP-CTX to irradiated tumor cells decreases the extracellular
activity of MMP-2. By targeting dispersed GBM cells and reducing MMP-2
activity, the combined use of CTX-nanovectors with radiotherapy may
represent a promising therapeutic approach toward GBM
Aptamer Functionalization of Nanosystems for Glioblastoma Targeting through the Blood–Brain Barrier
Polymeric nanoparticles (PNPs) may
efficiently deliver in vivo therapeutics to tumors when conjugated
to specific targeting agents. Gint4.T aptamer specifically recognizes
platelet-derived growth factor receptor β and can cross the
blood–brain barrier (BBB). We synthesized Gint4.T-conjugated
PNPs able of high uptake into U87MG glioblastoma (GBM) cells and with
astonishing EC<sub>50</sub> value (38 pM) when loaded with a PI3K-mTOR
inhibitor. We also demonstrated in vivo BBB passage and tumor accumulation
in a GBM orthotopic model
Synthesis of Lipophilic Core–Shell Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>@Au Nanoparticles and Polymeric Entrapment into Nanomicelles: A Novel Nanosystem for in Vivo Active Targeting and Magnetic Resonance–Photoacoustic Dual Imaging
In
this work, iron/silica/gold core–shell nanoparticles
(Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>@Au NPs) characterized
by magnetic and optical properties have been synthesized to obtain
a promising theranostic platform. To improve their biocompatibility,
the obtained multilayer nanoparticles have been entrapped in polymeric
micelles, decorated with folic acid moieties, and tested in vivo for
photoacoustic and magnetic resonance imaging detection of ovarian
cancer