2 research outputs found
Release of Anti-inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-inflammatory Cytokine Production
Pro-inflammatory
cytokines tumor necrosis factor α (TNF-α)
and interleukin 6 (IL-6) are mediators in the development of many
inflammatory diseases. To demonstrate that macrophages take up and
respond to thermosensitive nanoparticle drug carriers, we synthesized
PEGylated polyÂ(<i>N</i>-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate)
particles cross-linked with degradable disulfide (<i>N</i>,<i>N</i>′-bisÂ(acryloyl)Âcystamine) (NGPEGSS). An
anti-inflammatory peptide (KAFAK) was loaded and released from the
thermosensitive nanoparticles and shown to suppress levels of TNF-α
and IL-6 production in macrophages. Cellular uptake of fluorescent,
thermosensitive, and degradable nanoparticles and therapeutic efficacy
of free KAFAK peptide compared to that of KAFAK loaded in PEGylated
degradable thermosensitive nanoparticles were examined. The data suggests
that the degradable, thermosensitive nanoparticles loaded with KAFAK
may be an effective tool to treat inflammatory diseases
Development of Tumor-Targeted Near Infrared Probes for Fluorescence Guided Surgery
Complete surgical resection of malignant
disease is the only reliable
method to cure cancer. Unfortunately, quantitative tumor resection
is often limited by a surgeon’s ability to locate all malignant
disease and distinguish it from healthy tissue. Fluorescence-guided
surgery has emerged as a tool to aid surgeons in the identification
and removal of malignant lesions. While nontargeted fluorescent dyes
have been shown to passively accumulate in some tumors, the resulting
tumor-to-background ratios are often poor, and the boundaries between
malignant and healthy tissues can be difficult to define. To circumvent
these problems, our laboratory has developed high affinity tumor targeting
ligands that bind to receptors that are overexpressed on cancer cells
and deliver attached molecules selectively into these cells. In this
study, we explore the use of two tumor-specific targeting ligands
(i.e., folic acid that targets the folate receptor (FR) and DUPA that
targets prostate specific membrane antigen (PSMA)) to deliver near-infrared
(NIR) fluorescent dyes specifically to FR and PSMA expressing cancers,
thereby rendering only the malignant cells highly fluorescent. We
report here that all FR- and PSMA-targeted NIR probes examined bind
cultured cancer cells in the low nanomolar range. Moreover, upon intravenous
injection into tumor-bearing mice with metastatic disease, these same
ligand–NIR dye conjugates render receptor-expressing tumor
tissues fluorescent, enabling their facile resection with minimal
contamination from healthy tissues