Abstract
In this study, we prepared gold nanostar (GNS) composite nanoparticles containing siRNA of cyclooxygenase-2(siCOX-2) that were modified by tumor targeting ligand 2-deoxyglucose (DG) and transmembrane peptide 9-poly-D-arginine (9R) to form siCOX-2(9R/DG-GNS). Paclitaxel loaded temperature sensitive liposomes (PTX-TSL) were surface-modified to produce PTX-TSL-siCOX-2(9R/DG-GNS) displaying homogeneous star-shaped structures of suitable size (293.93 nm ± 3.21) and zeta potentials (2.47 mV ± 0.22). PTX-TSL-siCOX-2(9R/DG-GNS) had a high thermal conversion efficiency under 808 nm laser radiation and a superior transfection efficiency, which may be related to the targeting effects of DG and increased heat induced membrane permeability. COX-2 expression in HepG2/PTX cells was significantly suppressed by PTX-TSL-siCOX-2(9R/DG-GNS) in high temperatures. The co-delivery system inhibited drug-resistant cell growth rates by ≥77% and increased the cell apoptosis rate about 47% at elevated temperatures. PTX-TSL and siCOX-2 loaded gold nanostar particles, therefore, show promise for overcoming tumor resistance.
Highlights
Paclitaxel is widely administered to patients with breast and ovarian cancer and is beneficial to the treatment of lung and neck cancer [1,2]
Cells were transfected with Carboxyfluorescein (FAM) labeled small interfering RNAs (siRNAs) delivery systems (siCOX-2(GNS), siCOX-2(9R-gold nanostar (GNS)), siCOX-2(9R/DG-GNS), Paclitaxel loaded temperature sensitive liposomes (PTX-Temperature-sensitive liposome (TSL))-siCOX-2(9R/DG-GNS))
Compared to the Fourier transform infrared (FTIR) spectrum (Figure 1B) of free GNS, 9R/DG-GNS displayed a 1085 cm−1 stretching band for spectrum of HOOC-PEG-NH2 revealed that the emerging peak at 1111 cm−1 was the C-O-C in PEG, and the peak at 2885 cm−1 was attributed to C-H in PEG; the peak at 1734 cm−1 was due to the presence of C=O in PEG
Summary
Paclitaxel is widely administered to patients with breast and ovarian cancer and is beneficial to the treatment of lung and neck cancer [1,2]. New cytotoxic drugs have been developed for paclitaxel resistant ovarian cancer, but remission rates remain as high as 15%–25% [13]. TSL increases the release of encapsulated anticancer drugs at the tumor site [21,22]. Gold nanostars (GNS) are a new type of gold nanoparticle with excellent physical and chemical properties They are capable of converting light into heat when light irradiation’s wavelength coincides with the unable surface plasmon resonance (SPR) of GNS [27,28]. A co-delivery system of paclitaxel-loaded temperature sensitive liposomes (PTX-TSLs) and siCOX-2(9R/DG-GNS) was further constructed to form PTX-TSL-siCOX-2(9R/DG-GNS) (Figure 1). SiCOX-2(9R/DG-GNS) was taken up by drug-resistant tumor cells through the active targeting role of DG. The co-delivery of PTX-TSL-siCOX-2(9R/DG-GNS) was predicted to overcome paclitaxel resistance in cancer cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
