Conceptual representation of the nanoparticle-based multimodal anti-vascular strategy.Nanoparticles could transform cancer treatment by delivering drugs specifically to tumors, reducing drug dosages and unpleasant side effects. But it is difficult to get nanoparticles deep into solid tumor tissue. Instead, researchers in Spain are using nanoparticles to target the blood vessels that supply tumors with oxygen and nutrients to ‘starve’ cancer cells. [Paris et al., Acta Biomaterialia (2019), https://doi.org/10.1016/j.actbio.2019.11.004].
“Even though therapies directed towards tumor blood vessels are currently being used in the clinic, their effect in isolation is quite limited,” points out Vallet-Regí. “We wanted to showcase the concept of combining different types of therapeutic approaches directed towards tumor blood vessels in a single nanodevice,” she explains. “We believe this previously unexplored area could be very promising to maximize the efficacy of anti-vascular therapeutics in the context of cancer.”
There are two main types of anti-vascular agent that either compromise the ability of tumors to form new blood vessels or destroy those that have already formed. María Vallet-Regí and her team at Universidad Complutense de Madrid and CIBER-BBN designed mesoporous silica nanoparticles that can be loaded with both anti-angiogenic drugs (AADs) and vascular disrupting agents (VDAs). As well as delivering AAD and VDA drugs to the tumor’s blood vessels, gold nanorods in the core of the nanoparticles heat up when irradiated with near-infrared wavelengths to provide simultaneous photothermal treatment. Finally, a photosensitizer (Indocyanine Green) produces reactive oxygen species under irradiation, to add photodynamic therapy to the weaponry.
“This system provides four different effects aimed at destroying the tumor blood vessels,” says Vallet-Regí. “Fosbretabulin is a vascular disruption agent that destroys existing blood tumor vessels, while doxycycline acts as an antiangiogenic drug, inhibiting the production of new blood vessels by the tumor. When a NIR laser is applied, the nanoparticles produce heat and reactive oxygen species, which act locally in the tumor blood vessels, destroying the remaining vascular network.”
The nanoparticle system targets the endothelial cells lining the tumor’s blood vessels using a polyethylene glycol (PEG) chain that includes an RGD-containing peptide. One of the advantages of this approach is that nanoparticles do not need to penetrate deep into tissue to reach tumor blood vessels.
The researchers tested their nanoparticle system in cell culture and chicken embryos, monitoring the development of vasculature around tumor tissue. While the work is a proof-of-concept of a multimodal antivascular nanoparticle system, the researchers believe that approaches like this have significant potential to open new avenues for cancer treatment.
“The next step would be to modify the nanoparticle surface to include some component that could control the release of the drugs loaded inside the nanoparticle,” Vallet-Regí comments. “Significant work would be necessary to bridge the gap to animal models and eventually human application.”