Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

Abstract

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt ( P <0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer

“…The superior antitumor effect of Co-FA-NPs could be attributed to the targeting, the enhanced nanoparticles stability during the blood circulation, the sufficient and coinstantaneous delivery of two drugs to the tumor site, the efficient cellular uptake in the tumor, and the synergistic effect of CDDP and PTX on tumor inhibition. [ 40 ]…”

Nucleic Acid Aptamer-Guided Cancer Therapeutics and Diagnostics: the Next Generation of Cancer Medicine

“…Instead of developing new drugs, these studies explored a potential effective strategy that utilises a CSC-targeting moiety to deliver existing chemotherapeutic agents to eradicate both non-CSCs and CSCs. Most recently, RNA aptamers for targeting CSC markers (EpCAM and CD133) have been isolated 49 , 60 , 219 . Upon binding to cancer cells expressing these CSC markers, these CSC-targeting aptamers efficiently internalised via receptor-mediated endocytosis, an important mechanism capable of bypassing ATP-binding cassette transporters (ABC transporters) that are responsible for multiple drug resistance in CSC 60 , 100 .…”

Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy

“…In addition, the surface of PLGA nanoparticles can be modified with targeting moieties such as antibodies, proteins, and small molecules. [11] The present study found that the A10 aptamer-modified PLGA nanoparticles target to prostate cancer cells and are more effective at silencing the expression of the AR gene and decreasing cell viability than other treatments. We also found that the particle size, zeta potential and loading efficiency of TFO were not obviously changed, which is of great value for future clinical use.…”