4 research outputs found
Facial Layer-by-Layer Engineering of Upconversion Nanoparticles for Gene Delivery: Near-Infrared-Initiated Fluorescence Resonance Energy Transfer Tracking and Overcoming Drug Resistance in Ovarian Cancer
Development
of multidrug resistance (MDR) contributes to the majority of treatment
failures in clinical chemotherapy. We report facial layer-by-layer
engineered upconversion nanoparticles (UCNPs) for near-infrared (NIR)-initiated
tracking and delivery of small interfering RNA (siRNA) to enhance
chemotherapy efficacy by silencing the MDR1 gene and resensitizing
resistant ovarian cancer cells to drug. Layer-by-layer engineered
UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic
interaction. The delivery vehicle enhances MDR1-siRNA cellular uptake,
protects MDR1-siRNA from nuclease degradation, and promotes endosomal
escape for silencing the MDR gene. The intrinsic photon upconversion
of UCNPs provides an unprecedented opportunity for monitoring intracellular
attachment and release of MDR1-siRNA by NIR-initiated fluorescence
resonance energy transfer occurs between donor UCNPs and acceptor
fluorescence dye-labeled MDR1-siRNA. Enhanced chemotherapeutic efficacy
in vitro was demonstrated by cell viability assay. The developed delivery
vehicle holds great potential in delivery and imaging-guided tracking
of therapeutic gene targets for effective treatment of drug-resistant
cancers
Characteristics of Tumor Samples.
<p>Samples 1–28 derived from fresh frozen tissue; Samples 29–45 derived from formalin fixed paraffin embedded tissue.</p
Mass Spectrophotometry Plot: Observing a Mutation in SMARCB1.
<p>PCR products differ in mass depending on whether the probe extension detects a cytosine (C) or thymine (T). The figure in the right shows mass spec plot of an allele in SMARCB1 displaying a peak at both C and T. The left panel shows that most samples tested were homozygous with C, and 2 samples were heterozygous.</p
Selected View of aCGH Analyses (Chromosomes 9 and 10) from Two Cases.
<p>X-axis measures location along chromosome 9 (Panel A) or 10 (Panel B). Y-axis measures relative probe count. <b>A: aCGH showing heterozyogous copy loss at CDKN2A; B: aCGH showing heterozyogous copy loss at PTEN.</b></p