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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and
Kanpitcha Jiramitmongkon1,2,3, Pichayanoot Rotkrua3,4, Paisan Khanchaitit2
1Faculty of Science and Technology, Department of Chemistry, Thammasat University, Pathumthani, Thailand.
Abstract:
Colorectal cancer (CRC) poses a global health challenge, with current treatments often harming both cancerous and normal cells. To improve efficacy, a multifunctional drug delivery platform has been developed, integrating bioactive materials, anticancer agents, and targeted recognition ligands into a single molecule. This study aimed to create a molecular hybrid (MH) containing doxorubicin, AS1411 aptamer, and T9/U4 ASO to regulate SW480 cell proliferation. The AS1411 aptamer targets nucleolin, overexpressed on cancer cell membranes, while T9/U4 ASO inhibits human telomerase RNA activity, further hindering cancer cell proliferation. AS-T9/U4_MH was synthesized via oligonucleotide hybridization, followed by doxorubicin loading and evaluation of its impact on cell proliferation. Binding capability of this MH was verified using fluorescence microscopy and flow cytometry, demonstrating specific recognition of SW480 cells due to nucleolin availability on the cell surface. These findings were corroborated by both microscopy and flow cytometry. AS-T9/U4_MH exhibited anti-proliferative effects, with the doxorubicin-loaded system demonstrating encapsulation and reduced toxicity. Moreover, the presence of Dox within AS-T9/U4_MH led to a notable reduction in hTERT and vimentin expression in SW480 cells. Additionally, examination of apoptotic pathways unveiled a marked decrease in Bcl-2 expression and a simultaneous increase in Bax expression in SW480 cells treated with Dox-loaded AS-T9/U4_MH, indicating its impact on promoting apoptosis. This molecular hybrid shows promise as a platform for integrating chemotherapeutic drugs with bioactive materials for cancer therapy.
Insights
A new molecular hybrid combines chemotherapy with targeted aptamers and ASOs to fight colorectal cancer. This targeted approach shows promise for improved cancer therapy by reducing toxicity and promoting cancer cell death.
Area of Science:
- Biotechnology and Nanomedicine
- Molecular Oncology
- Drug Delivery Systems
Background:
- Colorectal cancer (CRC) presents a significant global health burden.
- Current CRC treatments lack specificity, often causing collateral damage to healthy cells.
- There is a critical need for advanced, targeted drug delivery platforms to enhance therapeutic efficacy and minimize side effects.
Purpose of the Study:
- To develop a multifunctional molecular hybrid (MH) for targeted colorectal cancer therapy.
- To integrate doxorubicin (chemotherapeutic agent), AS1411 aptamer (targeting nucleolin), and T9/U4 ASO (inhibiting telomerase) into a single platform.
- To evaluate the MH's efficacy in regulating SW480 cell proliferation and inducing apoptosis.
Main Methods:
- Synthesis of the AS-T9/U4_MH via oligonucleotide hybridization.
- Loading of doxorubicin onto the MH and characterization of encapsulation and release.
- Assessment of cell binding using fluorescence microscopy and flow cytometry.
- Evaluation of anti-proliferative effects and apoptosis induction in SW480 cells.
Main Results:
- The synthesized MH demonstrated specific binding to SW480 cells, attributed to nucleolin overexpression.
- Doxorubicin-loaded MH (Dox-loaded AS-T9/U4_MH) exhibited significant anti-proliferative activity and reduced toxicity.
- Treatment with Dox-loaded AS-T9/U4_MH downregulated hTERT and vimentin expression, decreased Bcl-2, and increased Bax, promoting apoptosis.
Conclusions:
- The developed molecular hybrid serves as a promising platform for integrating chemotherapeutic drugs with bioactive materials.
- This targeted approach offers potential for enhanced efficacy in colorectal cancer therapy.
- The MH's ability to induce apoptosis and reduce toxicity highlights its therapeutic potential.
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