Novel research has been undertaken in an attempt to decrease chemotherapy resistance to gemcitabine. A study published in the journal, Nano Today, has presented an antitumor strategy comprising nitrogen-doped carbon nanospheres.
Study: Reverse intratumor bacteria-induced gemcitabine resistance with carbon nanozymes for enhanced tumor catalytic-chemo therapy. Image Credit: chainarong06/Shutterstock.com
Chemotherapy Resistance
Resistance to chemotherapy has always been a concern within cancer treatments, with patients becoming resistant to chemotherapy drugs which can reduce the efficacy of the treatment, making cancer recurrence even more difficult to treat.
Interestingly, the addition of bacteria into the tumor microenvironment can be a factor that may contribute to the resistance of cancer chemotherapy drugs. Bacteria that express a long isoform of cytidine deaminase (CDD) can metabolize the anticancer drug, gemcitabine, into its inactive form, 2′, 2′-difluorodeoxyuridine, (dFdU), from its active form, 2′, 2′-difluorodeoxycytidine, (Gem).
The types of bacteria with this ability include Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Mycoplasma hyorhinis. Additionally, while the co-administration of antibiotics can kill bacteria which may improve the resistance against the anticancer drug, Gem, the overuse of antibiotics and antimicrobial resistance can cause difficulty when attempting to remove bacteria-induced inactivation.
This has led to the novel usage of nanotechnology and nitrogen-doped carbon nanospheres to possibly inhibit the CDD component which causes resistance against Gem.
Nitrogen-doped Carbon Nanospheres
Nanomaterials have seen extensive use, such as nanozymes in cancer treatment, biosensor development, and even antimicrobial effects. These novel materials have also been involved in eliminating tumor cells via reactive oxygen species generation.
This data has provided a premise for the current study with nanomaterials possibly illustrating inhibitory effects on CDD to retain the active state of Gem, which would enhance the efficacy of chemotherapy treatment and reduce resistance levels.
Nitrogen-doped carbon nanospheres (N-CSs) were chosen by the researchers due to their surface functionalization, large specific surface area, and the potential binding sites that may aid in their efficacy for CDD inhibition.
The researchers found the prepared nitrogen-doped carbon nanospheres reversed the bacterial CDD-induced gemcitabine resistance and effectively restored the tumors' susceptibility towards Gem chemotherapy. Additionally, this innovative approach also aided in catalyzing H2O2 within the tumor microenvironment resulting in the production of more cytotoxic hydroxyl (OH) radicals – effective for cancer treatment.
The effect of N-CSs within mouse tumor models with intratumor bacteria consisted of enhancing the efficacy of Gem in vivo as well as suppressing the growth of tumors, attributed to their dual functionality as CDD nanoinhibitors and peroxidase (POD)-like activity that can lead to highly cytotoxic OH radicals.
These anti-drug response observations have illustrated the potential of utilizing co-administration of N-CSs through synergizing gemcitabine and nanozyme-mediated catalytic therapy in order to overcome the obstacle of chemotherapy drug resistance for cancer treatment.
The Future of Enhancing Cancer Treatment
The significance of enhancing cancer treatment through this innovative nanotechnology interference includes increasing the efficacy of Gem chemotherapy which typically used to treat pancreatic, lung, breast and bladder cancer.
The N-doped carbon nanospheres research within this study has provided a promising future for drug-resistant chemotherapy treatments. Through the synergistic approach, which has allowed the bacterial CDD-induced component to be inhibited, the battle with chemotherapy resistance may be overcome.
With poor survival rates associated with pancreatic ductal adenocarcinoma, which has a 5-year survival rate of below 5%, this approach to overcoming resistance to Gem could truly be revolutionary for patient care.
The implication of this synergistic medical translation is significant, as gemcitabine resistance can develop within weeks of starting chemotherapy, which further decreases the survival and treatment efficacy for cancer therapeutics.
Additionally, with a high number of cancer cases diagnosed at a late stage, this only further reduces the survival rate with poorer prognoses given to patients. The two-fold realization of chemotherapy drug resistance upon initiating treatment can be traumatic for patients going through this arduous journey.
Cancer therapeutics can welcome this novel addition once translated after further in vivo research to confirm and provide significant and consistent positive results with mass co-administration.
This method of reducing resistance and increasing the efficacy of conventional chemotherapy drugs can be universalized and truly revolutionize the challenges faced in the field of cancer treatment.
Continue reading: Semiconducting Polymer Nanomaterials for Cancer and Tumor Treatment
Reference
Xi, J., Wang, Y., Gao, X., Huang, Y., Chen, J., Chen, Y., Fan, L. and Gao, L., (2022) Reverse intratumor bacteria-induced gemcitabine resistance with carbon nanozymes for enhanced tumor catalytic-chemo therapy. Nano Today, 43, p.101395. Available at: https://www.sciencedirect.com/science/article/pii/S1748013222000226
Further Reading
Binenbaum, Y., Na’ara, S. and Gil, Z., (2015) Gemcitabine resistance in pancreatic ductal adenocarcinoma. Drug Resistance Updates, 23, pp.55-68. Available at: https://doi.org/10.1016/j.drup.2015.10.002
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