Combination of designed liposomes and sonoporation provide drug release or immunomodulation
Résumé
Liposomes are extremely interesting to overcome some limitations of drugs, such as cytotoxicity, however, sometimes, liposomes are not sufficient by themselves to overcome the complexity of the environment, in particular in cancer, where the microenvironment limits the accessibility of tumor cells and reduces the potential effect of the designed systems. In order to overcome such limitations, it might be interesting to combine liposomes with physical trigger1. Moreover, associated imaging studies can help to understand the limits of the vectors and facilitate the design of the liposomes which should be associated to physical triggers.
To provide evidence of this interest, we designed liposomes filled with iron oxide nanoparticles to increase the amount of liposomes within the tumor and be able to follow this accumulation by MRI2. After determining the kinetic of accumulation, we could then apply ultrasound to deliver the CA4P encapsulated in thermosensitive liposomes. We could show that sonoporation and ferromagnetic liposomes using both MRI and bioluminescence allowed to enhance the delivery of the antiangiogenic agent CA4P3. We then tried to adapt this system for the delivery of nucleic acid. Combining sonoporation, lipoplexes activating TLR4 and pDNA encoding IL12, we aimed to induce immunostimulation to treat mice from their colon carcinoma4. The first proof of concept showed that stimulating the immune system, we could obtain a distal effect which is a good start, but this effect should be further amplified.