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Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug
Lei Li1, Dongxi Xiang2, Sarah Shigdar2
1College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China.
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.
Insights
Active targeted nanotechnology enhances anticancer treatment. Researchers developed curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles (CUR-NPs) functionalized with RNA Aptamers (Apts) for targeted delivery to colorectal cancer cells, improving efficacy and bioavailability.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Active targeted nanotechnology-based drug delivery systems offer potential for reduced side effects and improved efficacy in anticancer treatment.
- Colorectal cancer remains a significant health concern, necessitating innovative therapeutic strategies.
- Curcumin (CUR) possesses anticancer properties but suffers from poor bioavailability and targeted delivery.
Purpose of the Study:
- To synthesize and characterize curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles (CUR-NPs) functionalized with RNA Aptamers (Apts) targeting epithelial cell adhesion molecule (EpCAM).
- To evaluate the targeted delivery, cellular uptake, cytotoxicity, and in vivo bioavailability of Aptamer-functionalized CUR-NPs (Apt-CUR-NPs) in colorectal adenocarcinoma cells.
Main Methods:
- Synthesis and characterization of CUR-NPs and Apt-CUR-NPs, including particle size, zeta potential, drug encapsulation, stability, and release studies.
- In vitro assessment of specific cell binding, cellular uptake, and cytotoxicity against HT29 colon cancer cells.
- In vivo evaluation of CUR bioavailability from Apt-CUR-NPs compared to free CUR over 24 hours.
Main Results:
- Apt-CUR-NPs demonstrated significantly increased binding and cellular uptake in HT29 cells compared to control CUR-NPs (P<0.01).
- Apt-CUR-NP bioconjugates exhibited enhanced cytotoxicity against HT29 colon cancer cells.
- Encapsulation of CUR in Apt-CUR-NPs led to increased bioavailability of CUR over 24 hours compared to free CUR in vivo.
Conclusions:
- EpCAM Aptamer-functionalized CUR-NPs effectively enhance the targeting and drug delivery of curcumin to colorectal cancer cells.
- These nanocarriers show promise for improving the efficacy of colorectal cancer treatment.
- Further development of CUR-encapsulated nanosized carriers could advance targeted delivery of novel chemotherapeutic agents.
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