Micromaterials Made of Proteins Deliver Nanoparticles Which Attack and Destroy Specific Cancer Cells

According to the World Health Organization, colorectal cancer is the third most common cancer around the world, accounting for almost 10% of all cancer cases. It is also the second leading cause of cancer-related global deaths.

Early-stage colorectal cancer is entirely treatable with surgery and adjuvant therapy such as chemotherapy or radiotherapy. The recurrence, however, is common, and drug resistance increases the chance of treatment failure. While the treatment for other cancers has significantly improved, colorectal cancer management is not yet at a satisfactory level.

Novel Nanomaterials for Drug Delivery

At the Autonomous University of Barcelona, scientists have developed micromaterials that work by mimicking the natural secretory granules found in a person's endocrine system. The details of their study are described in the paper "Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids."

The research team is led by Professor Antonio Villaverde from the Institute of Biotechnology and Biomedicine of the Department of Genetics and Microbiology, in collaboration with experts from Sant Pau Research Institute and the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).

The self-contained micromaterials are made up only of proteins and can deliver the polypeptide that composes them over an extended period. The technology used for fabricating these granules is simple and mimics the secretory granules of the human endocrine system. Regarding its chemical structure, the micromaterials involve the coordination of ionic zinc with the histidine-rich domain. This amino acid is essential for living organisms, so it is not toxic.

The novel micromaterials Professor Villaverde and his colleagues developed are formed by amino acid chains called polypeptides. These substances are functional and bioavailable in nanoparticles that can be released and targeted to certain cancer cells to induce selective destruction.

The researchers analyzed the molecular structure of these micromaterials and the mechanism behind the secretion process, both in vitro and in vivo. In an animal model of CXCR4+ colorectal cancer, the system demonstrated high performance upon subcutaneous administration, with the released protein nanoparticles accumulated in tumor tissues.

The researchers noted that this accumulation is much more efficient than protein administered in blood. This provides an unexpected new way of ensuring high local drug levels and better clinical efficacy, preventing repeated intravenous administration regimens. The research team believes that in the clinical context, using these micromaterials to treat colorectal cancer can enhance drug efficiency and patient comfort while minimizing undesired side effects.

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How Does Endocrine Secretory Granules Work?

Endocrine secretory granules (ESGs) are organelles of endocrine or neuroendocrine cells which store hormones selectively. They are detected by electron microscopy as dense-cored spherical structures with a unit membrane. They also serve as important morphological markers for the pathological diagnosis of endocrine/neuroendocrine tumors.

ESGs are morphological characteristics of endocrine/neuroendocrine cells and work by storing peptide hormones/neurotransmitters. They contain prohormones and ESG-related molecules, mainly chromogranin/secretogranin family proteins.

ESGs are unique components of the cells in which neuropeptides are stored for secretion through the regulated secretory pathway (RSP) upon stimulation in neuroendocrine and endocrine cells. Therefore, secretory granule formation is a prerequisite to fulfilling the precise physiological functions of neuropeptides and hormones.

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