CHANG, RUN,SUN, LINLIN,WEBSTER, THOMAS JAY,MI, GUJIE
申请号：
CA2954545
公开号：
CA2954545A1
申请日:
2015.07.08
申请国别(地区):
CA
年份:
2016
代理人:
摘要：
Nanoparticulate carrier formulations are useful to solubilize, deliver, and target hydrophobic drugs for treating diseases including cancer and bacterial infections. The formulations contain amphiphilic peptides having a hydrophobic portion and a positively charged hydrophilic portion. The peptides self-associate at nonacidic pH to form micelles with a spherical nanoparticle morphology. The hydrophobic core of the nanoparticles encapsulates hydrophobic drugs, including antitumor agents, increasing their solubility in water and allowing them to be targeted, for example, to cancer cells. The positively charged surface of the nanoparticles, together with an optional targeting moiety such as an RGD peptide, allows the nanoparticles to bind selectively to mammalian cells and bacterial cells, including cancer cells that overexpress integrin receptors. The pH-dependence of the nanoparticle association/dissociation can be employed to conveniently load the nanoparticles with hydrophobic drug using a controlled pH shift, and unload them in acidic intracellular compartments. The ability of the carrier formulations to solubilize and target hydrophobic drugs gives rise to strategies for the selective inhibition or killing of cancer cells, such as the killing of osteosarcoma cells using the drug curcumin. The amphiphilic peptides and nanoparticles derived therefrom also give rise to additional compositions and methods that have useful bacteriocidal features as well as the ability to promote cell adhesion in cell scaffolds and coatings for medical implants.
