7 research outputs found
Folate-targeted nanostructured chitosan/chondroitin sulfate complex carriers for enhanced delivery of bortezomib to colorectal cancer cells
Folate-targeting self-assembled nanoparticles (NPs) using biocompatible and biodegradable natural polymers chitosan (Cs) and chondroitin sulfate (Chs) were developed to address the major challenge in cancer treatment, the selective delivery of nanoparticles to the target site. In this study, we successfully incorporated a hydrophobic drug, bortezomib (Bor), into folic acid (FA)-conjugated Cs/Chs self-assembled NPs (Bor/Cs/Chs-FA) for colorectal cancer therapy. The particle size and polydispersity index of Bor/Cs/Chs-FA were ∼196.5 ± 1.2 nm and ∼0.21 ± 0.5, respectively. A pH-dependent release profile was observed, facilitating cancer cell-targeted drug release under an acidic tumor microenvironment. Moreover, in vitro data revealed enhanced cellular uptake and apoptosis in folate receptor-expressing colorectal cancer cells (HCT-116 and HT-29) as compared to that in lung cancer cells (A549), which do not express folate receptors. Furthermore, intravenous administration of Bor/Cs/Chs-FA in a HCT-116 bearing xenograft mouse model showed that the NPs were a safe and effective drug delivery system. The results suggest that folate-targeted nanoparticle can be effectively applied for efficient chemotherapy of colorectal cancer. Keywords: Bortezomib, Chitosan chondroitin sulfate, Colorectal cancer, Folic aci
Polyamino Acid Layer-by-Layer (LbL) Constructed Silica-Supported Mesoporous Titania Nanocarriers for Stimuli-Responsive Delivery of microRNA 708 and Paclitaxel for Combined Chemotherapy
Cellular Fas-associated
protein with death domain-like interleukin-1β-converting enzyme-inhibitory
protein (c-FLIP), often strongly expressed in numerous cancers, plays
a pivotal role in thwarting apoptosis and inducing chemotherapy resistance
in cancer. An integrated approach combining chemotherapy with suppression
of c-FLIP levels could prove paramount in the treatment of cancers
with c-FLIP overexpression. In this study, we utilized a polymeric
layer-by-layer (LbL) assembly of silica-supported mesoporous titania
nanoparticles (MTNst) to co-deliver paclitaxel (PTX) and microRNA
708 (miR708) for simultaneous chemotherapy and c-FLIP suppression
in colorectal carcinoma. The resulting LbL miR708/PTX-MTNst showed
dose-dependent cytotoxicity in HCT-116 and DLD-1 colorectal carcinoma
cell lines, which was remarkably superior to that of free PTX or LbL
PTX-MTNst. LbL miR708/PTX-MTNst strongly inhibited c-FLIP expression
and resulted in increased expression of proapoptotic proteins. In
DLD-1 xenograft tumor-bearing mice, the nanoparticles accumulated
in the tumor, resulting in remarkable tumor regression, with the PTX
and miR708-loaded nanoparticles showing significantly greater inhibitory
effects than the free PTX or PTX-loaded nanoparticles. Immunohistochemical
analyses of the tumors further confirmed the remarkable apoptotic
and antiproliferative effects of the nanoparticles, whereas organ
histology reinforced the biocompatibility of the system. Therefore,
the LbL miR708/PTX-MTNst system, owing to its ability to deliver both
chemotherapeutic drug and inhibitory miRNA to the tumor site, shows
great potential to treat colorectal carcinoma in clinical settings