Cancer progression is significantly influenced by the activity of proteases, enzymes that break down proteins and play a critical role in tumor growth, metastasis, and the formation of new blood vessels (angiogenesis). Despite extensive research, clinical efforts to target proteases for cancer therapy have largely failed. Existing methods for detecting and analyzing protease activity in biological samples struggle with low sensitivity and poor selectivity, making it difficult to translate protease-targeting approaches into clinical applications. As a result, new, innovative solutions are urgently needed to improve the detection and use of protease activity in cancer diagnostics and treatment.
PROTECT aims to revolutionize the way we monitor and target protease activity in cancer by developing a comprehensive platform for protease profiling. This platform will address the limitations of current strategies, dramatically increasing sensitivity and the ability to simultaneously detect multiple proteases. By doing so, PROTECT will create new tools for personalized cancer therapy, tailoring treatments based on the specific protease activity profile of each patient’s tumor.
In PROTECT project two groundbreaking concepts are developed:
Liposomal Activity-Based Sensors (LABS) – These sensors will localize protease-responsive peptides to the tumor microenvironment, amplifying the protease activity by releasing synthetic biomarkers.
Protease Profile Specific Drug Delivery Vehicles (PROVES) – These liposomal systems will deliver encapsulated drugs directly to the tumor site, with high efficiency and specificity, triggered by the unique protease profile of the tumor.
PROTECT is structured around three core research tasks:
Development of Liposome-Conjugated proMAPs: The first task focuses on developing protease-responsive membrane-active peptides (proMAPs) that will be linked to liposomes. These peptides will trigger the release of synthetic biomarkers—encoded molecular barcodes—as a direct response to protease activity. This innovative system will allow us to track the activity of proteases in the tumor environment in real-time, with greater accuracy than current methods.
Multiplexed Protease Profiling: The second task involves developing methods to detect and analyze the release patterns of these barcodes, allowing us to correlate them with the activity of multiple cancer-associated proteases. This will enable robust multiplexed protease profiling, meaning that several proteases can be monitored simultaneously, providing a detailed picture of the tumor’s protease activity.
Precision Medicine Through Protease-Triggered Drug Delivery: The third task will focus on using the tumor’s unique protease profile to guide the release of drugs from liposomal delivery vehicles. These systems will be designed to release therapeutic agents specifically in response to the protease activity within the tumor microenvironment, ensuring targeted and efficient drug delivery. The effectiveness of this system will be evaluated in advanced in vitro 3D breast cancer models, which simulate the complex biological environment of a tumor.
The PROTECT project is expected to go far beyond current state-of-the-art technologies in cancer diagnostics and therapy. By integrating advanced peptide design with innovative lipid-nanoparticle systems, this project will develop highly sensitive and specific tools for monitoring protease activity and delivering drugs with unprecedented precision. This breakthrough could transform cancer treatment by enabling personalized therapies tailored to the protease activity profiles of individual tumors. In the long term, PROTECT has the potential to improve patient outcomes, reduce side effects of cancer treatments, and open new pathways for research into protease-targeted therapies. The success of PROTECT depends on a truly interdisciplinary approach, combining expertise in peptide chemistry, nanotechnology, cancer biology, and bioengineering. By working at the intersection of these disciplines, PROTECT is positioned to make significant contributions to both cancer diagnostics and therapeutics.
