The principle behind quadrapeutics involves four existing clinical treatments: radiotherapy, low-energy laser pulses, targeted drug delivery, and colloidal gold nanoparticles. The protocol was developed to treat chemoradiation-resistant tumors. Preclinical studies, led by Dmitri Lapotko at Rice University in Texas, recently showed a 17-fold improvement in treating aggressive, drug-resistant cancer in vivo. What’s more, the procedure specifically targeted cancer cells, leaving healthy cells unharmed.
Four components work together to combat cancer cells
Concurrently administered components work together to target and destroy cancer cells. The first is a delivery system composed of drug-loaded nanocarriers, such as liposomes or micelles. The second component is a colloidal suspension of 60 nm solid gold particles. Both the nanocarriers and the nanoparticles are functionalized with an antibody against epidermal growth factor receptor (EGFR). The high level of EGFR expressed by cancer cells results in a correspondingly high concentration of internalized particles. In effect, the cancer cells self-assemble intracellular nanoclusters composed of the endocytosed particles.
When the nanoclusters are exposed to the third component, a laser pulse, plasmonic nanobubbles are produced, which expand and burst in a matter of nanoseconds. The mechanical forces generated have a number of effects, including the destruction of tumor cells and the release of the drug from the nanocarriers. Thus, cells that survive are subjected to significantly magnified doses of chemotherapeutic agents. Gold nanoclusters also serve to amplify the effects of the fourth component, radiotherapy.
All four elements work synergistically to eliminate tumors. Findings indicate that the treatment is effective against head and neck squamous cell carcinoma in mice at drug dosage levels as low as 3% and radiation levels as low as 6% of the current standard.
Quadrapeutics picks up where chemoradiation is forced to leave off
The results are far-reaching. Currently, the residual portions of tumors that cannot be fully resected are treated with a combination of chemotherapy and radiation. When the tumors become resistant, however, clinicians are left with little recourse. Quadrapeutics offers a way to overcome this resistance, while at the same time minimizing toxicity to surrounding tissue.
The technology has the potential to be applicable to the treatment of various types of drug- and radiation-resistant tumors, in addition to the ones targeted in the study. The low drug and radiation doses involved also make it ideal for treating cancer in younger patients.
Preclinical study results and an overview of the protocol can be found in Nature Medicine.