3 research outputs found
Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment
A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose <i>via</i> intravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold <i>in vitro</i> and led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system
PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers
Herein
we report the potential of click chemistry-modified polypeptide-based
block copolymers for the facile fabrication of pH-sensitive nanoscale
drug delivery systems. PEG–polypeptide copolymers with pendant
amine chains were synthesized by combining <i>N</i>-carboxyanhydride-based
ring-opening polymerization with post-functionalization using azide–alkyne
cycloaddition. The synthesized block copolymers contain a polypeptide
block with amine-functional side groups and were found to self-assemble
into stable polymersomes and disassemble in a pH-responsive manner
under a range of biologically relevant conditions. The self-assembly
of these block copolymers yields nanometer-scale vesicular structures
that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin
at physiological pH but that fall apart spontaneously at endosomal
pH levels after cellular uptake. When drug-encapsulated copolymer
assemblies were delivered systemically, significant levels of tumor
accumulation were achieved, with efficacy against the triple-negative
breast cancer cell line, MDA-MB-468, and suppression of tumor growth
in an in vivo mouse model
Thermal Switching of the Reflection in Chiral Nematic Mesoporous Organosilica Films Infiltrated with Liquid Crystals
Materials
that undergo stimulus-induced optical changes are important for many
new technologies. In this paper, we describe a new free-standing silica-based
composite film that exhibits reversible thermochromic reflection,
induced by a liquid crystalline guest in the pores of iridescent mesoporous
films. We demonstrate that selective reflection from the novel mesoporous
organosilica material with chiral nematic organization can be reversibly
switched by thermal cycling of the 8CB guest between its isotropic
and liquid crystalline states, which was proven by solid-state NMR
experiments. The switching of the optical properties of the chiral
solid-state host by stimulus-induced transitions of the guest opens
the possibility of applications for these novel materials in sensors
and displays