Team:SYSU-CHINA/Improve
Future Work - Improvement
In evaluation of the valuable statistics we obtained from our previous modelling, experiments and human practice integrations, we have thought deeper into the possibility of extending our project to an upper level and made plans for future researches and applications.
“Plans for the drug administration mode”
Both from our human practice work and further investigations into finding a more applicable method in drug delivery, we decided to alter our original drug dosing methods using enema or suppository and recommended a more promising and effective mode, hydrogel, in our drug administration. We compared the advantages and disadvantages of different kinds of drug dosing modes literatures-based, as shown in the table.
As we can see, although suppository and enema can partly achieve local drug delivery, the administration time and area are too limited. Intestinal stents can meet the needs of long-term administration, but it is easily shifted and needs to be replaced regularly. In light of this, we recommended a recently emerged hydrogel-based drug delivery system, which relies on a physically and chemically crosslinked hydrogel to stably release drugs if it’s activated by particular molecules [3]. Although this method is still at experimental stage, its high biocompatibility, convenience and high efficiency make us more convinced that it will eventually be applied clinically. Therefore, we intended to test our system along with this drug dosing method in future verification examinations.
“Raising virus titer by modifying the adenovirus vector”
Statistics acquired from our modelling work elucidated that higher the virus titer our system produced, more efficient they are in targeting and terminating colon cancer cells. The modelling data also showed that repeated administration can improve the effect in treating cancer. By means of hydrogel-based drug-dosing system, we might realize continuous administrating to the cancer tissues. But its efficiency ought to be further measured by our following work.
However, according to our experimental data, the recombination efficiency of our adenovirus system was far from perfect. We planned to modify our adenovirus system by replacing the protein fibers on viral capsid from adenovirus type 5 (what we are using now) to adenovirus type 22, and added a layer of or a domain of targeting protein on the viral capsid, by means of molecular cloning. Their expression efficiency differences in eukaryotic cell lines or even tissues could alter be investigated by constructing eukaryotic expression vectors. We intend to test the effect of the combination of the refined adenovirus vector system with our chosen drug-delivery method, for higher the virus titer produced and repeated administration.
“Expanding our experiments from human cell lines to a larger extent”
We have tested the efficiency of the engineered adenovirus vector system on HEK293, but we still have a long way to go before our project could be safely applied in clinical use. If certain matches of the “hydrogel” administration method worked coordinately with our remodified adenovirus vector, we plan to extend this system to a larger scale, from human cell lines, to colon cancer cell lines, cancer tissues on model animals, and eventually to clinical tests. Actually, the miRNA profile in our designed system could be artificially reorganized to suit different cancer types, with great possibility of realizing precision medicine at individual level. Additionally, we can further text on multidrug combinations to achieve a better therapeutic effect.
References
[1] Sepantafar, Mohammadmajid, et al. “Engineered Hydrogels in Cancer Therapy and Diagnosis.” Trends in Biotechnology 35.11(2017).
[2] Park, Semi , et al. "Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction." Yonsei Medical Journal 50.2(2009).
[3] English, Max A., et al. "Programmable CRISPR-responsive smart materials." Science 365.6455 (2019): 780-785.