Scientists design peptides to enhance drug efficacy

(Press-News.org) NEW YORK, NY, January 24, 2025 — A team of scientists has developed a groundbreaking approach using specially designed peptides to improve drug formulations. This innovative method significantly enhances anti-tumor efficacy, as demonstrated in leukemia models. The study, published in the journal Chem, was led by researchers at the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) and Memorial Sloan Kettering Cancer Center.

Drug delivery systems often face two critical challenges: poor solubility and inefficient delivery within the body. Many drugs do not dissolve well, making it difficult for them to reach their intended targets. Furthermore, current delivery systems waste a significant portion of the drug during preparation—only 5–10% of the drug is successfully loaded, leading to less effective treatments.

Peptide Helpers

The research team has developed a novel solution by designing peptides—short strings of amino acids—to bind with specific drugs and create therapeutic nanoparticles. These nanoparticles are primarily composed of the drug, with a thin peptide coating that improves solubility, enhances stability in the body, and optimizes delivery to targeted areas. Remarkably, this approach achieves drug loadings of up to 98%, a dramatic improvement over traditional methods.

By using a combination of computer models and laboratory tests, new drug/peptide nanoparticles where identified. They subsequently demonstrated remarkable results in leukemia models. The nanoparticles were more effective at shrinking tumors compared to the drugs alone. Additionally, their high efficiency allows for lower doses of drugs, potentially reducing the side effects.

“Peptides, which are designed molecules made from the same building blocks as the proteins in our body, are extremely versatile,” said Co-Principal Investigator Rein Ulijn, director of the Nanoscience Initiative at CUNY ASRC and a chemistry professor at Hunter College. “We thought they could be useful in solving two big problems seen in many drugs: poor solubility and inefficient delivery. By designing a peptide that binds the drug while enhancing its solubility, we were able to create nanoparticles with very high loading.”

Customizable Technology

This innovation holds significant potential because peptides can be customized to enhance the effectiveness of various drugs. Given the vast range of possible interactions in peptide design, it may be feasible to tailor peptides for specific drugs, extending their applicability beyond cancer treatments.

“This breakthrough enables the development of better precision medicines,” said Co-Principal Investigator Daniel Heller, head of the Cancer Nanomedicine Laboratory at Memorial Sloan Kettering Cancer Center’s Molecular Pharmacology Program. “Using specially designed peptides, we can build nanomedicines that make existing drugs more effective and less toxic and even enable the development of drugs that might not be able to work without these nanoparticles."

Naxhije “Gia” Berisha, a former CUNY Graduate Center Ph.D. student who performed much of the experimental work, highlighted the potential of the peptide approach: “We used experimental testing to identify promising peptides and computational modeling to analyze their interactions with therapeutic molecules,” she said “It’s incredible to see how simple variations in peptide sequence could match specific drugs. This suggests there may be a peptide match for every drug, potentially revolutionizing the way medicines are delivered.”

Looking Ahead

The research team is now adopting lab automation methods to further refine and accelerate the peptide-drug matching process. Their next steps include verifying the approach’s potential in a wider range of diseases. If successful, this innovation could lead to more effective treatments, reduced side effects, and significant cost savings in drug development.

DOI is 10.1016/j.chempr.2024.102404

About the Advanced Science Research Center at the CUNY Graduate Center
The Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) is a world-leading center of scientific excellence that elevates STEM inquiry and education at CUNY and beyond. The CUNY ASRC’s research initiatives span five distinctive, but broadly interconnected disciplines: nanoscience, photonics, neuroscience, structural biology, and environmental sciences. The center promotes a collaborative, interdisciplinary research culture where renowned and emerging scientists advance their discoveries using state-of-the-art equipment and cutting-edge core facilities.

About the Graduate Center of The City University of New York
The CUNY Graduate Center is a leader in public graduate education devoted to enhancing the public good through pioneering research, serious learning, and reasoned debate. The Graduate Center offers ambitious students nearly 50 doctoral and master’s programs of the highest caliber, taught by top faculty from throughout CUNY — the nation’s largest urban public university. Through its nearly 40 centers, institutes, initiatives, and the Advanced Science Research Center, the Graduate Center influences public policy and discourse and shapes innovation. The Graduate Center’s extensive public programs make it a home for culture and conversation

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