3 research outputs found
Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Resonance–Computed Tomography Image Guided Radiation Therapy
Selective
killing of cancer cells while minimizing damage to healthy tissues
is the goal of clinical radiation therapy. This therapeutic ratio
can be improved by image-guided radiation delivery and selective radiosensitization
of cancer cells. Here, we have designed and tested a novel trimodal
theranostic nanoparticle made of bismuth and gadolinium for on-site
radiosensitization and image contrast enhancement to improve the efficacy
and accuracy of radiation therapy. We demonstrate in vivo magnetic
resonance (MR), computed tomography (CT) contrast enhancement, and
tumor suppression with prolonged survival in a non-small cell lung
carcinoma model during clinical radiation therapy. Histological studies
show minimal off-target toxicities due to the nanoparticles or radiation.
By mimicking existing clinical workflows, we show that the bismuth–gadolinium
nanoparticles are highly compatible with current CT-guided radiation
therapy and emerging MR-guided approaches. This study reports the
first in vivo proof-of-principle for image-guided radiation therapy
with a new class of theranostic nanoparticles
Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy
More than 50% of all cancer patients
receive radiation therapy. The clinical delivery of curative radiation
dose is strictly restricted by the proximal healthy tissues. We propose
a dual-targeting strategy using <i>vessel</i>-<i>targeted</i>-radiosensitizing gold nanoparticles and <i>conformal</i>-image guided radiation therapy to specifically amplify damage in
the tumor neoendothelium. The resulting tumor vascular disruption
substantially improved the therapeutic outcome and subsidized the
radiation/nanoparticle toxicity, extending its utility to intransigent
or nonresectable tumors that barely respond to standard therapies
Passive versus Active Tumor Targeting Using RGD- and NGR-Modified Polymeric Nanomedicines
Enhanced
permeability and retention (EPR) and the (over-) expression
of angiogenesis-related surface receptors are key features of tumor
blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp
(RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received
considerable attention in the last couple of years. Using several
different in vivo and ex vivo optical imaging techniques, we here
visualized and quantified the benefit of RGD- and NGR-based vascular
vs EPR-mediated passive tumor targeting. This was done using ∼10
nm sized polymeric nanocarriers, which were either labeled with DY-676
(peptide-modified polymers) or with DY-750 (peptide-free polymers).
Upon coinjection into mice bearing both highly leaky CT26 and poorly
leaky BxPC3 tumors, it was found that vascular targeting did work,
resulting in rapid and efficient early binding to tumor blood vessels,
but that over time, passive targeting was significantly more efficient,
leading to higher overall levels and to more efficient retention within
tumors. Although this situation might be different for larger carrier
materials, these insights indicate that caution should be taken not
to overestimate the potential of active over passive tumor targeting