Virus‐Like Particle‐Encapsulated Doxorubicin Enters and Kills Murine Tumor Cells Differently from Free Doxorubicin

• Published in: Macromolecular bioscience 2023-06, Vol.23 (6), p.e2200530-n/a
• Main Authors: Gonçalves, Amanda P., Ramos, José Ésio B., Madureira, Karoline H., Martins, Marcelo L., Santos, Anésia A., de Vries, Renko
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Aspect ratio; Autophagy; Cancer; Cell Line, Tumor; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - pharmacology; DNA viruses; Doxorubicin; Doxorubicin - chemistry; Drug Carriers - chemistry; Drug Carriers - pharmacology; drug delivery systems; Drug Delivery Systems - methods; Encapsulation; Endocytosis; Melanoma; Mice; Nanoparticles; Nanoparticles - chemistry; Polypeptides; Side effects; Toxicity; Tumor cells; Tumors; Viruses; virus‐like particles
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202200530

The use of nanoparticles as chemotherapeutic carriers has been suggested as a way to overcome a range of side effects associated with classical cancer treatment such as poor selectivity and tumor resurgence. Obtaining precise control of the size and shape of therapeutic nanoparticles is crucial to optimize the targeting of tumor sites. In this work, it is shown that a previously developed system of polypeptide encapsulating individual DNA molecules, that forms rod‐shaped nanoparticles of precisely controlled aspect ratio, can be loaded with the DNA‐intercalating chemotherapeutic drug doxorubicin (DOX). It is characterized the size and shape of the DOX loaded‐Virus‐Like DNA Particles (DOX‐VLDP) and shown that in this system the DOX payload does not leak out. Through in vitro cell studies, it is shown that DOX‐VLDP is internalized by melanoma tumor cells (B16F10 cells) in a delayed and endocytosis‐dependent way culminating in increased cytotoxicity and selectivity to tumor cells in comparison with free DOX. In addition, it is found that DOX‐VLDP trigger apoptosis and autophagy pathways in treated cells. Taken together, the data on the DOX‐VLDP nanoparticles shows that they kill cancer cells differently from free DOX. This study shows that encapsulated dsDNA molecules can load doxorubicin (DOX) by intercalation and this new nano‐carrying model promotes DOX internalization on murine melanoma cells, which occurs in a different way when compared to free DOX. Further, cytotoxicity is increased when DOX is encapsulated and both apoptosis and autophagy cell death pathways are triggered.