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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
Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
Fengjiao Yao1, Yacong An1, Xundou Li1
1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Purpose:
Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells.
Methods:
The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox.
Results:
Apt-HJ had an average size of 12.45 nm and a zeta potential of -11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects.
Conclusion:
These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.
Insights
A novel DNA nanostructure (Apt-HJ-Dox) effectively targets and delivers doxorubicin to colon cancer cells, enhancing anti-tumor efficacy in vivo while minimizing side effects.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Chemotherapy for advanced colon cancer causes severe toxicities, limiting its effectiveness.
- Selective drug delivery systems (SDDS) offer a strategy to mitigate adverse effects.
- Developing practical, scalable SDDS for targeted colon cancer therapy is crucial.
Purpose of the Study:
- To design a novel, biocompatible, and scalable SDDS for targeted doxorubicin (Dox) delivery to colon cancer cells.
- To create a DNA nano-cross functionalized with AS1411 aptamers for enhanced cancer cell binding.
- To evaluate the efficacy and safety of the Dox-loaded SDDS in colon cancer treatment.
Main Methods:
- A DNA nano-cross (Holliday junction, HJ) was functionalized with four AS1411 aptamers (Apt-HJ).
- Doxorubicin (Dox) was loaded into the Apt-HJ structure via intercalation, forming Apt-HJ-Dox.
- In vitro and in vivo studies were conducted using CT26 colon cancer cells and control cells.
Main Results:
- The Apt-HJ-Dox complex demonstrated selective binding and uptake by CT26 colon cancer cells.
- Apt-HJ-Dox effectively killed colon cancer cells in vitro and reduced damage to normal cells.
- In vivo studies showed enhanced antitumor efficacy of Apt-HJ-Dox compared to free Dox, without increased adverse effects.
Conclusions:
- The Apt-HJ-Dox system shows significant potential for targeted colon cancer treatment.
- This novel SDDS offers a promising approach to improve chemotherapy outcomes.
- Further development could lead to practical clinical applications for colon cancer therapy.
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