'Quadrapeutics' makes cancer cells explode

Colloidal gold is the explosive, a near infrared laser pulse the detonator in a new anti-cancer technology developed by researchers from Rice University, the University of Texas MD Anderson Cancer Center and Northeastern University. They coined their method quadrapeutics. It consists of a novel combination of existing clinical treatments that instantaneously detects and kills cancer cells without harming healthy tissue. InNature Medicine they report that it was 17 times more efficient than conventional chemoradiation therapy against aggressive, drug-resistant head and neck tumours.

Quadrapeutics was designed to address aggressive cancers that cannot be efficiently and safely treated, like tumours that are intertwined with important organs or have become resistant to chemoradiation. Quadrapeutics differs from other cancer treatments in that it radically amplifies the intracellular effect of drugs and radiation only in cancer cells. The quadrapeutic effects are achieved by mechanical events - tiny, remotely triggered nano-explosions called ‘plasmonic nanobubbles’. Plasmonic nanobubbles are non-stationary vapors that expand and burst inside cancer cells in response to a short, low-energy laser pulse.

"Quadrapeutics shifts the therapeutic paradigm for cancer from materials - drugs or nanoparticles - to mechanical events that are triggered on demand only inside cancer cells," Dmitri Lapotko, the study’s lead investigator said. "Another strategic innovation is in complementing current macrotherapies with microtreatment. We literally bring surgery, chemotherapies and radiation therapies inside cancer cells."

The first component of quadrapeutics is a low dose of a clinically validated chemotherapy drug. The team tested encapsulated versions of doxorubicin and paclitaxel that were tagged with antibodies to target cancer cells. Thanks to the magnifying effect of the plasmonic nanobubbles, the intracellular dose is very high even when the patient receives only a few percent of the typical clinical dose.
The second component is an injectable solution of nontoxic gold colloids, also tagged with cancer-specific and clinically approved antibodies that cause them to accumulate and cluster together inside cancer cells. These gold ‘nanoclusters’ do nothing until activated by a laser pulse, which is the third quadrapeutic component. The investigators used short near-infrared laser pulses. A standard endoscope delivers the laser pulse to the tumour, where the gold nanoclusters convert the laser energy into plasmonic nanobubbles.

The fourth component is a single, low dose of radiation. The gold nanoclusters also amplify the deadly effects of radiation only inside cancer cells, even when the overall dose to the patient is just a few percent of the typical clinical dose.

Head and neck

In the Nature Medicine study, the team tested quadrapeutics against head and neck squamous cell carcinoma (HNSCC) that had grown resistant to both chemotherapy drugs and radiation.¹ Quadrapeutics proved so deadly against HNSCC that a single treatment using just 3 percent of the typical drug dose and 6 percent of the typical radiation dose effectively eliminated tumours in mice within one week of the administration of quadrapeutics.

Lapotko is now working with colleagues at MD Anderson and Northeastern to move as rapidly as possible toward prototyping and a human clinical trial. In clinical applications, quadrapeutics will be applied as either a stand-alone or intra-operative procedure using standard endoscopes and other clinical equipment and encapsulated drugs such as Doxil or Lipoplatin. Lapotko believes that quadrapeutics is a universal technology that can be applied for local treatment of various solid tumours, including other hard-to-treat types of brain, lung and prostate cancer. He said it might also prove especially useful for treating children due to its safety.

Reference
1. Lukianova-Hleb EY, et al. Nat Med 2014 Jun 1. doi: 10.1038/nm.3484. [Epub ahead of print]