What a pleasure it has been to host Erem Bilensoy, Sümeyra Pancur and Nurbanu Demirtürk for a short secondment in our facilities and discuss the next steps of our collaboration.
There are so many synergies between Hacettepe University and our company that it will be difficult to pick the most promising topic.
As cancer remains one of the most challenging diseases to treat, scientists have developed various medications and therapeutic approaches to combat it. To protect drugs from degradation or inactivation, efficient delivery systems are required during administration. In this context, cyclodextrin-based polymeric nanosystems have emerged as an effective treatment approach against cancer.
Cyclodextrins are natural oligosaccharides that can trap water-insoluble molecules inside their hydrophobic core, making them valuable in pharmaceutical research. When combined with polymeric nanoparticles, CD-based delivery systems provide versatile and tunable profiles, thanks to the submicron-sized PNPs. Recent studies have shown that CD-based delivery systems can successfully be applied in combination therapy and theranostics, providing multifunctional advantages against cancer.
The article by Lakshmi Sathi Devi, Cristina Casadidio, Maria Rosa Gigliobianco, Piera Di Martino and Roberta Censi from University of Camerino further discusses different binding approaches, release mechanisms of CD-drug complexation, and characterization studies. Promoting CD to a polymeric and nanoscale has demonstrated improved tumor targeting, reduced side effects, and prolonged drug release in preclinical studies and clinical trials. Notably, CD-based delivery systems, including CALAA-01, CRLX101, and CRLX301, have shown promising results in treating cancer.
Overall, cyclodextrin-based polymeric nanosystems hold great potential in tackling the abnormalities behind cancer by providing an efficient drug delivery system.
We have known for a while that methylated β-cyclodextrin (MβCD) can extract cholesterol from lipid rafts and induce apoptosis in cancer cells by inhibiting activation of the PI3K-Akt-Bad pathway.
In this study from Kumamoto University (Keiichi Motoyama), MβCD with mannose (Man-MβCD) is assessed for targeting colon cancer cells expressing the mannose receptor (MR) and tumor-associated macrophages (TAM). Man-MβCD showed a significantly greater level of cellular association with colon-26 cells and M2 macrophages, and much more prominent anticancer activity than that of MβCD against MR-positive colon-26 cells. These results revealed that autophagy was the main mechanism of cell death associated with Man-MβCD. Furthermore, compared with MβCD, Man-MβCD significantly reduced tumor development following intravenous delivery to tumor-bearing mice, with no apparent side effects. Thus, Man-MβCD has the potential to be a novel anticancer drug.
If you would like to try something like this, check out this site for ideas: Custom synthesis of cyclodextrins – www.carbohydesolutions.com
More and more uses of cyclodextrin as anticancer therapy agents come to light these days. The most recent is the research of Kumamoto University (who else) showing how Folate-Appended Hydroxypropyl-β-Cyclodextrin (FA-HP-β-CyD) Induces Autophagic Cell Death in Acute Myeloid Leukemia (AML) Cells.
As reported the cytotoxic activity of FA-HP-β-CyD against AML cells was stronger than that of HP-β-CyD. Also, FA-HP-CyD induced the formation of autophagosomes in AML cell lines. FA-HP-β-CyD increased the inhibitory effects of cytarabine and a BCL-2-selective inhibitor, Venetoclax, which are commonly used treat elderly AML patients. Notably, FA-HP-β-CyD suppressed the proliferation of AML cells in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double-deficient mice with AML. These results suggest that FA-HP-β-CyD acts as a potent anticancer agent for AML chemotherapy by regulating.
We believe that using cyclodextrin for targeted delivery of molecules is certainly one of the applications that will be in future’s research focus.
In this patent that we bring today as a good example, a camptothecin derivative and cyclodextrin polyrotaxane are subjected to a click chemical reaction under the catalysis of copper, and the cyclodextrin supramolecular drug for targeted delivery of camptothecin is obtained by using active folate termination. Cell experiments show that the compound has good targeting selectivity and anti-tumor effect, and also has the advantage of small toxic and side effects.
What a great day! One of our youngest, Kristóf Felegyi just placed another brick in the wall of his PhD with this article about isolating and identifying novel polyporenic acids and triterpenes from Buglossoporus quercinus. The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.
Nice work and way to go, Kristof!
Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer, highlight their biology, emphasizes the current understanding of resistance mechanisms, and focuses on promising strategies that are under investigation. Current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients are also collected.
Novel targets for immune-checkpoint inhibition in cancer – Cancer Treatment Reviews
today’s cyclodextrin:
Breast cancer is a global burden with the most severe subtype being triple-negative breast cancer (TNBC). Despite advances in conventional therapies, treatment for TNBC is currently lacking. Interestingly, cholesterol has gained interest as a potential therapeutic target due to cancer cells’ increased reliance on this macromolecule. Treatment with the cholesterol-depletory agent 2-hydroxypropyl-β-cyclodextrin (HPβCD) impeded the growth of cancer cells and further led to cancer cell death, which could be attributed to an altered cellular cholesterol profile following treatment. Furthermore, mice xenograft studies indicated complete eradication of early-stage tumours with no relapse, followed by a remarkable reduction in intermediate- and late-stage tumours, respectively. SFRP1 was identified as a possible molecular target facilitating the therapeutic action of HPβCD. These findings consequently potentiate cholesterol depletion as a novel anticancer strategy to be pursued.
University of the Witwatersrand – Tawanda Ziningav Reubina Wadee, Mandeep Kaur et al
Have you known that certain animals are unable to develop cancer? Do you also know why?
Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly, and are highly prone to cancer. They have been very useful for modeling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique traits of very high value to humans, such as cancer resistance and longevity. In recent years, several discoveries have been made in non-standard mammalian species, providing new insights into the natural mechanisms of cancer resistance. These include mechanisms of cancer resistance in the naked mole rat, blind mole rat, and elephant. In each of these species, evolution took a different path, leading to novel mechanisms. Many other long-lived mammalian species display cancer resistance, including whales, grey squirrels, microbats, cows, and horses. Understanding the molecular mechanisms of cancer resistance in all these species is important and timely, as, ultimately, these mechanisms could be harnessed for the development of human cancer therapies.
See the full article here on nature.com
Radioactive iodine may cause thyroid cancer and hypofunction and accordingly must be properly managed. If the absorption of radioactive iodine is suppressed, it can be expected to lead to a reduction in thyroid exposure. This study the inhibition of radioactive iodine absorption by the oral administration of α-cyclodextrin is shown in a murine model. The uptake of radioactive iodine into the thyroid gland in mice administered with radioactive iodine and an α-cyclodextrin solution was approximately 40% lower after 24 h. The finding that oral uptake of α-cyclodextrin has an inhibitory effect on the transfer of radioactive iodine to the thyroid gland has potential for application in many fields such as food, pharmaceuticals, nuclear emergency preparedness, and medicine.
Kumamoto University, JAPAN
See the full article on nature.com
