Integrating Nanoparticles Into Chemotherapy

Researchers at Brigham and Women’s Hospital designed novel, multi-functional, self assembled, near-infrared responsive gold nanorods, which can selectively target cancer cells by releasing a chemotherapy drug and triggering induction of heat synergistically. Irradiation using NIR light is an ideal method for thermal ablation by activating nanoparticles and penetrating deep tissue noninvasively. Zintro experts discuss how effective this thermo-chemotherapy method will be for cancer treatments.

As oncologist Jaroslaw Jac indicates, this treatment more likely falls into the local therapy category and must be measured against standard of care approaches, such as surgery and radiation therapy, which set up high bar to overcome. “There are certainly limitations to where light can be used as an activator, and there is no mentioning of the way of targeted delivery and why the nanoparticles are specifically targeted to the cancer cells,” notes Jac. “Antibody-cytotoxic drug conjugates has been developed and Mylotarg was approved for AML and subsequently withdrawn, and Adcetris is approved for HL and anaplastic large cell lymphoma. So the question is what differential advantage use of nanoparticles would have?”

Christopher S. Lange, professor of radiation oncology and molecular & cell biology, doesn’t consider the suggested approach to be feasible for curative treatments since the targeting of the cancer stem cells (CSCs), is in its infancy. “The concept of NIR responsive gold nanorods to release a chemotherapy agent that has increased specificity and toxicity at an elevated temperature, generated by the NIR interaction with the gold nanorods is potentially interesting for paliative tumor treatment, but the real problem is in the specificity of the targeting and how much time the paliation would provide,” he explains. Another problem Lange finds with the hyperthermia approach is that in many cases, the circulation quickly dissipates any heat provided, except perhaps to necrotic volumes having poor circulation and most of the cells in these volumes are moribund. “We have recently shown (Radiation Research Society 2012 Meeting) that for the best characterized breast cancer biomarker combination (CD24-CD44+CD326+), which selects 1-2% of the tumor cells, only 1% of these cells (0.02% of tumor) are functional CSCs. Our Hybrid Spheroid Assay measures the fraction of tumor composed of CSCs and their sensitivities to proposed treatments. This approach has both curative and paliative potentials,” he adds.

Gareth Hughes, an expert in biomedical engineering and medical nanotechnologies, believes that using a targeted, thermal-mediated approach to deliver highly potent drugs to only the cancer cells will greatly reduce the potential of unwanted, off-target effects. “While chemotherapy is well established and can be very effective in treating cancer, the potential of off-target effects from chemotherapeutic agents is well known. These side effects can be just as challenging to manage as the cancer itself,” he notes.

By Idil Kan

 

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