Biologically targeted nanoparticles may boost radiation therapy effects

Oct 27, 2011

(PhysOrg.com) -- Making a tumor more sensitive to radiotherapy is a primary goal of combining chemo and radiation therapy to treat many types of cancer, but with the chemotherapy drugs come unwanted side effects.

UNC scientists report what they believe is the first pre-clinical demonstration of the potential of molecularly targeted nanoparticles as a promising new class of agents that can improve chemoradiotherapy treatment. The nanoparticles target , thus sparing normal tissue and avoiding the systemic side effects often associated with . They reported their finding in the October 19, 2011 Epub issue of the American Chemical Society publication ACS Nano.

The team used the drug docetaxel, used to treat head and neck cancers. Andrew Wang, MD, assistant professor of and senior study author explains, “Docetaxel is a proven drug used in chemoradiotherapy, but it leads to many unwanted side effects on normal organs. Nanoparticle formulation of docetaxel, on the other hand, concentrates in tumors, which in turn leads to improved efficacy and fewer side effects.”

“We developed a biodegradable nanoparticle formulation of docetaxel that targets the folate receptor, overexpressed in head and neck and other tumors. Folate is a water-soluble form of Vitamin B9.  We found that the folate-targeted nanoparticle was more effective than the docetaxel or non-targeted nanoparticle formulation of docetaxel. We also learned that timing of the radiation following administration of the nanoparticle formulation is critical.  

“This information will be very helpful in the clinical translation of nanoparticle drugs in chemoradiation. Our group is currently evaluating two commercial formulations of nanoparticle taxane drugs in preparation for early phase clinical trials in the near future.”

Explore further: Innovative strategy to facilitate organ repair

More information: Folate-targeted Polymeric Nanoparticle Formulation of Docetaxel is an Effective Molecularly Targeted Radiosensitizer with Efficacy Dependent on the Timing of Radiotherapy, ACS Nano, Just Accepted Manuscript. DOI: 10.1021/nn203165z

Abstract
Nanoparticle (NP) chemotherapeutics hold great potential as radiosensitizers. Their unique properties, such as preferential accumulation in tumors and their ability to target tumors through molecular targeting ligands, are ideally suited for radiosensitization. We aimed to develop a molecularly targeted nanoparticle formulation of docetaxel (Dtxl) and evaluate its property as a radiosensitizer. Using a biodegradable and biocompatible lipid-polymer NP platform and folate as a molecular targeting ligand, we engineered a folate-targeted nanoparticle (FT-NP) formulation of Dtxl. These NPs have sizes of 72±4 nm and surface charges of -42±8 mV. Using folate receptor over-expressing KB cells and folate receptor low HTB-43 cells, we showed folate-mediated intracellular uptake of NPs. In vitro radiosensitization studies initially showed FT-NP is less effective than Dtxl as a radiosensitizer. However, the radiosensitization efficacy is dependent on the timing of radiotherapy. In vitro radiosensitization conducted with irradiation given at the optimal time (24 hours) showed FT-NP Dtxl is as effective as Dtxl. When FT-NP Dtxl is compared to Dtxl and non-targeted nanoparticle (NT-NP) Dtxl in vivo, FT-NP was found to be significantly more effective than Dtxl or NT-NP Dtxl as a radiosensitizer. We also confirmed that radiosensitization is dependent on timing of irradiation in vivo. In summary, FT-NP Dtxl is an effective radiosensitizer in folate-receptor over-expressing tumor cells. Time of irradiation is critical in achieving maximal efficacy with this nanoparticle platform. To the best of our knowledge, our report is the first to demonstrate the potential of molecularly targeted NPs as a promising new class of radiosensitizers.

Related Stories

Polymeric nanoparticles attack head and neck cancer

Jul 15, 2011

Head and neck cancer, the sixth most common cancer in the world, has remained one of the more difficult malignancies to treat, and even when treatment is successful, patients suffer severely from the available therapies. ...

New nanoparticles could improve cancer treatment

Oct 05, 2010

In recent years, studies have shown that for many types of cancer, combination drug therapy is more effective than single drugs. However, it is usually difficult to get the right amount of each drug to the ...

Targeted Nanoparticles Destroy Prostate Tumors

Apr 25, 2006

Biodegradable polymer nanoparticles, linked to a protein-binding nucleic acid known as an aptamer and loaded with the anticancer agent docetaxel, can target and kill prostate tumors growing in mice. Using this targeted nanoparticle ...

Therapeutic nanoparticles targeted to radiation treated tumors

Mar 28, 2011

Radiation and chemotherapy are common partners in anticancer therapy for solid tumors, but too often, the combined side effects associated with each mode of therapy can limit how aggressively oncologists can treat their patients. ...

Recommended for you

Innovative strategy to facilitate organ repair

Apr 18, 2014

A significant breakthrough could revolutionize surgical practice and regenerative medicine. A team led by Ludwik Leibler from the Laboratoire Matière Molle et Chimie (CNRS/ESPCI Paris Tech) and Didier Letourneur ...

Physicists create new nanoparticle for cancer therapy

Apr 16, 2014

A University of Texas at Arlington physicist working to create a luminescent nanoparticle to use in security-related radiation detection may have instead happened upon an advance in photodynamic cancer therapy.

User comments : 0

More news stories

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...