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Molecular hybrid containing anticancer drug and recognizing colorectal cancer cells |
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| รหัสดีโอไอ | |
| Title | Molecular hybrid containing anticancer drug and recognizing colorectal cancer cells |
| Creator | Kanpitcha Jiramitmongkon |
| Contributor | Boonchoy Soontornworajit, Advisor |
| Publisher | Thammasat University |
| Publication Year | 2568 |
| Keyword | Doxorubicin, Antisense oligonucleotides, AS1411 aptamer, Nucleolin, Hybridization, Colorectal cancer, ด็อกโซรูบิซิน, แอนไทเซนส์โอลิโกนิวคลีโอไทด์, แอปตาเมอร์ AS1411, นิวคลีโอลิน, ไฮบริไดเซชัน, มะเร็งลำไส้ใหญ่ |
| Abstract | Colorectal cancer (CRC) constitutes a major public health burden both in Thailand and globally, necessitating the development of more effective treatments. Nevertheless, current therapeutic strategies remain constrained by limited specificity and efficacy. To overcome these challenges, a multifunctional drug delivery platform was developed by incorporating bioactive materials with specific recognition ligands into a unified molecular construct. Aptamers could function as specific binding ligands for cancer treatment formulation. They are short single-stranded synthetic chemical DNA or RNA sequences. These agents possess the ability to bind target molecules with high affinity and specificity. Therefore, the aptamers were used as recognition agents in the drug delivery systems. In addition, antisense oligonucleotides (ASOs) interrupt transcription processes resulting in specifically inhibiting or silencing target mRNA pathways. This research aimed to construct a multifunctional drug delivery system that contains AS1411 aptamer, T9/U4 ASO, and doxorubicin for regulating C cell proliferation. Due to the specific affinity of AS1411 aptamer for nucleolin, a protein abundantly expressed on the cell membrane of various cancers. T9/U4 ASO suppressed cancer cell proliferation by inhibiting human telomerase RNA activity. Research activities for this project are as follows: i) AS-T9/U4 molecular hybrid (AS-T9/U4_MH) was prepared by oligonucleotide hybridization ii) aptamer train (AT) was formed through hybridization and ligation reaction. The anti-cancer drugs doxorubicin (Dox) and mitoxantrone (MTZ) were loaded into AS-T9/U4_MH and AT, respectively. Evaluation of the effects of anti-cancer drug–loaded molecular hybrids on cell proliferation was performed using the MTS assay. Subsequently, the molecular hybrid capable of binding was assessed via flow cytometry and fluorescence microscopy. The results showed that AS-T9/U4_MH and AT specifically recognize C cells because they have nucleolin on their surface. Moreover, AS-T9/U4_MH and AT showed antiproliferation. Dox and MTZ loaded systems showed that Dox and MTZ were encapsulated resulting in less toxicity. These results suggest that the multifunctional drug delivery system is a promising system for incorporating other chemotherapeutic drugs to other bioactive materials and the delivery system would be used for cancer treatment. |
