Combination of paclitaxel- and retinoic acid-incorporated nanoparticles for the treatment of CT-26 colon carcinoma

Abstract

The aim of this study was to evaluate the antitumor effect of combinatorial targeted therapy with paclitaxel and all-trans retinoic acid (ATRA) nanoparticles in vitro. Paclitaxel-incorporated pullulan acetate (PA) nanoparticles were prepared by the nanoprecipitation-solvent evaporation method. ATRA-incorporated nanoparticles were prepared by dialysis using a methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) copolymer. Particle sizes of paclitaxel-incorporated nanoparticles and ATRA-incorporated nanoparticles were about 160 nm and 60 nm, respectively. Nanoparticles were reconstituted in various aqueous media such as deionized water, phosphate-buffered saline, and fetal bovine serum-supplemented cell culture media. The combination of paclitaxel + ATRA (10 + 10 μg/mL) delivered by nanoparticles showed a synergistic antiproliferative effect against CT26 cells that was not observed with other combinations. Furthermore, the activity of MMP-2, a key enzyme in tumor cell invasion, was significantly decreased in cells treated with the combination of paclitaxel and ATRA while other combinations and single agents did not significantly affect its activity. A matrigel assay supported these results, indicating that paclitaxel/ATRA combination nanoparticles are effective for the inhibition of the invasion of tumor cells. The results of the present study suggest that combination treatment with paclitaxel and ATRA could be an effective treatment for the inhibition of tumor cell proliferation and invasion, and that nanoparticles are promising candidates for antitumor drug delivery.

All‐trans retinoic acid reverses epithelial‐mesenchymal transition in paclitaxel‐resistant cells by inhibiting nuclear factor kappa B and upregulating gap junctions

“…ATRA is commonly used in combination with paclitaxel to improve patient outcomes . It has been reported that this combination is effective for inhibition of the invasion of tumor cells . In our study, it was confirmed that, as a single agent, ATRA reverses the upregulation of EMT in paclitaxel‐resistant colorectal cancer cell lines.…”

“…The combination of all‐ trans ‐retinoic acid (ATRA) and paclitaxel has been used to treat a variety of cancers for more than 10 years. This combination causes more apoptosis and less invasion than paclitaxel alone . ATRA is the predominant natural metabolite of vitamin A and is involved in many important biological processes, such as morphogenesis, vision, growth, metabolism, differentiation, and cellular homeostasis .…”

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

“…In clinical use, ATRA combined with paclitaxel (a clinically used drug for cancer) was used to treat a variety of cancer patients for more than 10 years and the treatment of both combination (ATRA and paclitaxel) led to increasing cancer cell apoptosis and inhibiting cell invasion than that of paclitaxel alone (Hong et al, 2011;Karmakar, Banik, & Ray, 2008). Therefore, we used the combination of ATRA and BDMC to treat Hep 3B cells and results displayed that combined treatment induced higher cell apoptosis than that of ATRA or BDMC only.…”

Multilayered pore‐closedPLGAmicrosphere deliveringOGPandBMP‐2 in sequential release patterns for the facilitation ofBMSCs osteogenic differentiation

“…Sun et al and Lee et al found that, porous PLGA microspheres carrying human serum albumin and insulin released 88.7% and 50% of the two biofactors within 1 day, respectively. Furthermore, although some studies have explored the codelivery of multiple biofactors, in most cases different biofactors were released simultaneously instead of sequentially . Sequential release of multiple biofactors from one carrier, which is technically more difficult, is thought to offer important advantages, because different signals may be required at different stages of bone healing.…”