Drug Augmented, Light-Activated Nanoparticles Effectively Kill Cancer Cells

The inclusion of a chemotherapeutic agent within a novel class of light-sensitive nanoparticles enhanced their ability to kill cancer cells.

Investigators at Duke University (Durham, NC, USA) have been working with light-activated nanoparticles that they fabricated by synthesizing a thin, thermally responsive poly(N-isopropylacrylamide-co-acrylamide) hydrogel coating directly onto the surfaces of individual near-infrared (NIR) absorbing gold-silica nanoshells.

This hydrogel was designed to be in a swollen state under physiological conditions and expel large amounts of water, along with any entrapped drug, at elevated temperatures. The required temperature change was achieved via NIR absorption by the nanoshell, allowing the hydrogel phase change to be triggered by light, which was observed by monitoring changes in particle sizes as water was expelled from the hydrogel network.

As a further refinement, the investigators used these light sensitive nanoparticles as carriers to deliver the chemotherapeutic drug doxorubicin (DOX). Although in use for more than 40 years as a primary chemotherapy drug, DOX is known to cause serious heart problems. To prevent these, doctors may limit the amount of DOX given to each patient so that the total amount a patient receives over her or his entire lifetime is 550 milligrams per square meter, or less. Furthermore, the necessity to stop treatment to protect the patient from heart disease may diminish the usefulness of DOX in treating cancer.

Results published in the June 10, 2015, online edition of the journal ACS Biomaterials Science & Engineering revealed that exposure to NIR light triggered rapid release of doxorubicin from the nanoparticle delivery vehicles. Colon carcinoma cells exposed to the irradiated platform displayed nearly three times as much doxorubicin uptake as cells exposed to non-irradiated particles or free drug, which in turn resulted in a higher loss of cell viability. The increased uptake of DOX might have been due to the NIR-mediated heating of the nanoparticles, which caused a transient increase in cell membrane permeability, thus aiding in cellular uptake of the drug.

"The idea is to combine tumor-destroying heat therapy with localized drug delivery, so that you can hopefully have the most effective treatment possible," said senior author Dr. Jennifer West, professor of bioengineering at Duke University. "And many chemotherapeutic drugs have been shown to be more effective in heated tissue, so there's a potential synergy between the two approaches. The hydrogels can release drugs just above body temperature, so you could potentially look at this for other drug-delivery applications where you do not necessarily want to destroy the tissue. You could do a milder warming and still trigger the drug release."

The potential use of light-sensitive nanoparticle therapy is being investigated for several types of cancers at Nanospectra Biosciences, Inc. (Houston, TX, USA), a company founded by Dr. West.

Related Links:
Duke University
Nanospectra Biosciences, Inc.