H2: Groundbreaking approach uses cyclic peptide nanotubes to deliver doxorubicin to cancer cell nuclei
A team at CiQUS (University of Santiago de Compostela, Spain) has unveiled a novel molecular strategy that enables anticancer drugs to reach the nucleus of tumor cells, enhancing their therapeutic impact. Focusing on doxorubicin, a cornerstone chemotherapy drug, the researchers show that drug resistance can be overcome without compromising antitumor activity. The work represents a promising new direction in cancer treatment, where drug delivery systems bypass cells’ protective barriers to restore drug efficacy.
H2: How cyclic peptide nanotubes work in cancer cells
H3: Self-assembly into nanotubes
The core idea hinges on cyclic peptides—small rings of amino acids—that can stack and self-assemble into hollow cylindrical nanotubes on the surface of cancer cell membranes. This self-assembly creates a stable, tube-like conduit that can ferry therapeutic molecules into cells in a controlled manner.
H3: Targeted delivery to the nucleus
In this strategy, doxorubicin is chemically linked to the cyclic peptide. Once bound to the negatively charged surfaces more prevalent on cancer cell membranes, the peptide–drug conjugate is internalized and directed toward the nucleus. This nuclear delivery route is distinct from doxorubicin’s traditional intracellular trafficking and helps the drug circumvent common resistance mechanisms that typically reduce its effectiveness.
H2: Why cancer cells are particularly vulnerable to this approach
H3: Membrane composition and selectivity
Cancer cell membranes often contain higher levels of negatively charged lipids compared with healthy cells. The cyclic peptides display a strong affinity for these anionic surfaces, promoting selective interaction with tumor cells. This selectivity is crucial for minimizing off-target effects while maximizing drug dosing within malignant cells.
H3: Enhanced penetration and sustained activity
The chemical structure of the cyclic peptide is key to forming stable nanotubes, which in turn enhances their ability to penetrate malignant cells. By stabilizing the peptide assembly, the system ensures efficient transport of doxorubicin to the nucleus, where the drug intercalates with DNA to trigger cytotoxic damage in cancer cells.
H2: Implications for overcoming drug resistance and future directions
H3: Overcoming resistance mechanisms
Drug resistance remains a major hurdle in cancer therapy, with tumor cells exploiting drug efflux pumps and other adaptive processes to reduce treatment efficacy. The cyclic peptide nanotube approach acts as a highly efficient delivery vehicle, facilitating the entry of doxorubicin into resistant cells and delivering it to an intracellular compartment where it can exert its cytotoxic effect.
H3: Toward new combination chemotherapies
This research opens the door to potential new therapeutic strategies that combine peptide-based nanotechnology with conventional chemotherapy. By adapting the peptide scaffold, researchers may tailor delivery pathways for different drugs, potentially addressing a range of hard-to-treat tumors.
H2: About the study and its broader impact
H3: Collaboration and support
The study was conducted at CiQUS and published in ACS Applied Materials & Interfaces. CiQUS is recognized as a CIGUS by the Xunta de Galicia and supported by the European Union through the Galicia FEDER Programme 2021–2027, underscoring the project’s strategic importance and funding backbone.
H3: Looking ahead
The authors emphasize that while the results are promising, further work is needed to optimize the balance between stability, selectivity, and release kinetics, and to evaluate the approach across diverse tumor models. If successful, peptide-based nanotube delivery could complement existing chemotherapies, enabling lower drug doses with preserved antitumor activity and reduced resistance.
H2: Conclusion
The cyclic peptide nanotube strategy represents an innovative and potentially transformative route to counteract cancer drug resistance. By leveraging the natural propensity of cyclic peptides to form hollow nanotubes and coupling them to doxorubicin, researchers are charting a path toward more effective, nucleus-targeted cancer therapies that can keep pace with evolving tumor defenses.
