Researchers develop novel covalent organic structures for precise delivery of cancer treatment

A team of researchers from New York University Abu Dhabi (NYUAD), led by Chemistry Program Director Ali Trabolsi, has developed nanoscale covalent organic frameworks (nCOFs), crystalline organic polymers that have been modified with peptides to treat the most aggressive form of breast cancer, known as triple-negative breast cancer (TNBC).

Peptides enable COFs to release the drug payload in the acidic environment of the tumor, ensuring that high concentrations of the drug are delivered directly to the tumor site. This increases the efficacy of treatment while minimizing the impact on healthy tissue.

This new treatment method offers hope for a new approach to treating triple-negative breast cancer, which tends to grow and spread more quickly than other forms of breast cancer. It has fewer treatment options and generally has a poorer prognosis.

Although peptides have been used for targeted delivery before, their conjugation with COFs represents an innovative approach in this field. In the article entitled “Covalent organic frameworks modified by cRGD peptides for precision chemotherapy in triple-negative breast cancer” published in the journal ACS Applied Materials and InterfacesThe researchers describe the process of designing alkyne-functionalized nCOFs that were chemically modified with cyclic RGD peptides (Alkyn-nCOF-cRGD).

This configuration was designed to specifically target α_vβ₃ nCOFs are biocompatible and have been designed to selectively disintegrate under acidic conditions, allowing the precise and localized release of doxorubicin, a chemotherapeutic agent encapsulated in nCOFs.

Farah Benyettou, a key researcher on the team, said: “Our innovative approach using COFs conjugated to peptides offers a highly targeted treatment method for triple negative breast cancer. By focusing on the acidic environment of tumours, we can deliver chemotherapy precisely where it is needed most, reducing side effects and improving patient outcomes. The peptides act as a key to unlock the door of the cancer cells, allowing the drug to enter and exert its effects exactly where it is needed.”

This research is particularly important in the United Arab Emirates, where breast cancer rates are particularly high. Existing drug delivery systems often have significant drawbacks, such as non-specific distribution, fluctuations in plasma drug concentrations, rapid clearance, and side effects on healthy tissues. The positive in vitro and in vivo results of this study not only highlight the advanced targeting capabilities of nCOFs, but also set new standards for personalized cancer therapy.

“Our research has created a smarter way to fight the most aggressive and invasive form of breast cancer,” Trabolsi said.

“By providing a targeted approach to cancer treatment, this technology not only fills existing gaps in drug delivery research, but also represents a crucial step towards personalized medicine in cancer treatment that is both more effective and less harmful to patients,” Benyettou said.