Researchers develop new covalent organic framework for precise targeting of cancer treatment

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

The peptides enable the COF to release the drug within the acidic environment of the tumor, delivering high concentrations of the drug directly to the tumor site, enhancing the efficacy of the treatment while minimizing the impact on healthy tissue.

This new therapy holds promise as a new treatment for triple-negative breast cancer, a disease that tends to progress and spread more quickly than other types of breast cancer, has few treatment options and typically has a poor prognosis.

While peptides have been used for targeted delivery in the past, conjugation with COFs is an innovative approach in the field. In a paper published in ACS Applied Materials & Interfaces titled “cRGD Peptide-Modified Covalent Organic Frameworks for Precision Chemotherapy of Triple-Negative Breast Cancer,” the researchers describe the design process of an alkyne-functionalized nCOF chemically modified with a cyclic RGD peptide (Alkyn-nCOF-cRGD).

This construct was designed to specifically target αvβ3 integrin, which is overexpressed in TNBC cells. The nCOF is biocompatible and designed to selectively degrade under acidic conditions, allowing precise and localized release of the chemotherapeutic drug doxorubicin encapsulated in the nCOF.

Farah Benietou, the team’s lead researcher, said: “Our innovative approach using peptide-linked COFs offers a highly targeted treatment for triple-negative breast cancer. By focusing on the acidic environment of the tumour, we can deliver chemotherapy exactly where it is needed most, reducing side effects and improving patient outcomes. The peptide acts like a key that opens the door on the cancer cell, allowing the drug to get in and have its effect exactly where it is needed.”

This study is particularly relevant in the UAE, where the incidence of breast cancer is significantly higher. Existing drug delivery systems often suffer from significant drawbacks, including non-specific distribution, fluctuating plasma levels of the drug, rapid clearance, and side effects on healthy tissues. The successful in vitro and in vivo results of this study not only highlight the advanced targeting capabilities of nCOF, but also establish a new standard for personalized cancer therapy.

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

“By providing a targeted approach to cancer therapy, this technology not only fills an existing gap in drug delivery research, but also represents an important step towards personalized medicine that is more effective in treating cancer and less harmful to patients,” said Benietu.