Periodic Reporting for period 1 - MucOncoBots (Drug-loaded nanobots for transmucosal delivery to mucinous tumours)
Période du rapport: 2023-10-01 au 2025-03-31
Pseudomyxoma peritonei (PMP) is a rare form of abdominal cancer characterized by the excessive production of mucus that envelops cancerous cells. This mucus barrier protects the tumor and reduces the effectiveness of traditional chemotherapy. Current treatments for PMP rely on an aggressive and invasive surgical approach, followed by the direct infusion of chemotherapy into the abdomen. However, this standard treatment is associated with high recurrence rates. One of the main limitations is the persistent presence of mucus, which prevents the drugs from reaching all cancerous cells, leaving untreated pockets that may lead to relapse.
To address this clinical challenge, the MucOncoBots project set out to develop an innovative therapeutic approach using self-propelled nanoparticles, capable of breaking down the mucus barrier while delivering anti-cancer drugs directly to the tumor site. The nanobots were engineered to carry and release Mitomycin C, an existing anti-cancer drugs, enhancing its local effect. The goal was to create a single technology that could overcome the physical barriers of the disease and deliver treatment more effectively and less invasively.
To address this clinical challenge, the MucOncoBots project set out to develop an innovative therapeutic approach using self-propelled nanoparticles, capable of breaking down the mucus barrier while delivering anti-cancer drugs directly to the tumor site. The nanobots were engineered to carry and release Mitomycin C, an existing anti-cancer drugs, enhancing its local effect. The goal was to create a single technology that could overcome the physical barriers of the disease and deliver treatment more effectively and less invasively.
During the course of the project, we successfully designed and synthesized mesoporous silica-based nanobots powered by catalase, an enzyme that decomposes hydrogen peroxide into oxygen and water. Besides being needed for the propulsion of the nanomotors, hydrogen peroxide also helped in disrupting the mucin structure, effectively liquefying the mucus barrier. The nanobots were loaded with Mitomycin C, drugs already used for PMP treatment.
In collaboration with the Vall d’Hebron Institute of Oncology (VHIO), we tested these nanobots in advanced preclinical models, including patient-derived organoids and mouse models. The nanobots demonstrated superior inhibition of tumor cell growth compared to the drug alone, in ex vivo samples.
In collaboration with the Vall d’Hebron Institute of Oncology (VHIO), we tested these nanobots in advanced preclinical models, including patient-derived organoids and mouse models. The nanobots demonstrated superior inhibition of tumor cell growth compared to the drug alone, in ex vivo samples.
The MucOncoBots project represents a significant step forward in overcoming one of the major challenges in treating mucinous cancers like PMP: the physical barrier posed by mucus. Unlike existing treatments that rely on invasive surgery and passive drug diffusion, our approach introduces a paradigm shift—combining autonomous motion, mucus degradation, and drug delivery into one therapeutic vehicle. This all-in-one solution enables more effective targeting of cancerous tissues while reducing the need for aggressive procedures and minimizing systemic side effects.