Multifunctional nanoparticles with synergistic photothermal and chemotherapeutic effects show promise for cancer treatment.
Curing cancer is one of the grand biomedical challenges of the twenty-first century and the design of functional nanoparticles to meet this challenge is an emerging field of nanobiotechnology. Sun-Mi Lee and colleagues at Yonsei University in Korea1 have now prepared multifunctional nanoparticles that allow near infrared (NIR) imaging of cancer tumors and can induce photothermal and cytotoxic tumor cell death.
Lee’s team encapsulated doxorubicin, a highly toxic anticancer drug, within nanoparticles consisting of poly(ethylene glycol) (PEG) and poly(lactic-co-glycolic acid) (PLGA). The loaded nanoparticles were then arranged as a monolayer on a silicon substrate, and a thin gold film was deposited over the exposed hemispheres of the nanoparticles. The gold surface was further coated with PEG-based molecules (Fig. 1) to reduce the nonspecific adsorption of proteins onto the nanoparticles and thus enhance their stability in physiological solution. The gold hemispheres absorb NIR light, which can be used in vivo for both imaging and therapy.
Nanoparticles introduced intravenously into mice with skin cancer accumulated in the tumor region through a well-known nanoparticle permeability and retention effect. The nanoparticles were also detected at low concentrations in other organs, but with no toxic effect. Intratumoral injection led to a more concentrated accumulation of nanoparticles at the location of the tumor.
The concentration of nanoparticles can be observed by NIR imaging, but exposure of the nanoparticle to NIR irradiation also causes the particles to resonate, generating heat and releasing the cargo — doxorubicin. After only ten minutes of exposure to NIR light, the temperature increase led to enhanced and sustained release of doxorubicin from these nanoparticles. The increase in temperature caused by the nanoparticles under exposure to NIR light was also sufficient on its own to induce irreversible tumor damage, even when doxorubicin was not present.
Activating both mechanism of the functionalized nanoparticles — doxorubicin delivery and photothermal therapy — resulted in completed destruction of tumors in seven days, a result that could not have been achieved using doxorubicin or photothermal therapy alone.
“This synergistic effect is ascribed to enhanced cytotoxicity of doxorubicin at elevated temperature and a higher heat sensitivity for the cells exposed to doxorubicin,” says Lee.
References
Lee, S-M., Park, H-Y. & Yoo, K-H. Synergistic cancer therapeutic effects of locally delivered drug using multifunctional nanoparticles. Adv. Mater. 22, 4049 (2010).
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Nanobiotechnology: Heat-assisted cancer therapy. NPG Asia Mater (2010). https://doi.org/10.1038/asiamat.2010.161
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DOI: https://doi.org/10.1038/asiamat.2010.161