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Innovative Strategy in Nanomedicine for Targeted Cancer Therapy: Laser-triggered nanoplatform enabling site-specific drug delivery

Innovative Strategy in Nanomedicine for Targeted Cancer Therapy:

Laser-triggered nanoplatform enabling site-specific drug delivery

Due to its unique size effects, nanomedicine can take advantage of the enhanced permeability and retention effect (EPR) to preferably accumulate in tumor tissue after systematic administration. To further improve this targeting efficacy, some targeting ligands are often attached on the surface of nanomedicine. It is expected that these ligands can recognize and bind to the target for active targeting therapy. However, in vivo performance of many ligand-modified tumor-targeted nanoparticles is not as good as initially envisioned, because ligand attachment often decreases their blood circulation time and ligand affinity to receptors instead of improving their biodistribution. External stimuli such as ultrasound and magnetic field have also been applied to trigger in vivo tumor targeting. Locally applied external heating can also induce site-specific accumulation of intravenously injected thermal-responsive polymers and their payloads. These novel tumor targeting strategies could be very efficient to enhance the selectivity of certain effects since the timing and intensity of the stimuli can be precisely controlled.

Drs. Chunying Chen and Xiaochun Wu’s group at the National Center for Nanoscience and Technology of China have been working closely on the bio-effects and safety studies of gold nanorods, and their biomedical applications as well. In previously studies, they developed a core-shell nanostructure, mesoporous silica coated-gold nanorods (Au@SiO2) for laser controlled tumor therapy in cell lines. A chemotherapeutic drug can be efficiently loaded into the mesopores of Au@SiO2 and the release can be controlled with laser irradiation.

The two groups have proceeded to coat a thermoresponsive polymer onto the surface of Au@SiO2 and developed a thermoresponsive nanocomposite, Au@SiO2@polymer. In this nanocomposite, the photothermal properties of gold nanorods and the thermoresponsive properties were successfully integrated: the gold nanorods transform the photo energy to heat which raise the temperature, leading the thermoresponsive polymer layer to shrink. That is, laser irradiation can decrease the size of Au@SiO2@polymer, and consequently trigger the release of pre-absorbed drug. (Figure 1)

These properties were applied on mouse xenograft tumor models for laser controlled targeted tumor therapy. After systematic administration, the tumor was irradiated by laser immediately. The nanocomposites diffused in the bloodstream shrank and started to extravagate from tumor vessels and accumulated in tumor tissue after laser irradiation. The tumor accumulated nanocomposite showed synergetic thermo-chemotherapy which almost achieved tumor extinction. (Figure 1)

Since laser can be manipulated very precisely and flexibly, the nanocomposite provides an ideally versatile platform to simultaneously deliver heat and anticancer drugs in a laser-activation mechanism with facile control of the area, time, and dosage. The NIR laser-induced targeted cancer thermo-chemotherapy without using targeting ligands demonstrates a novel anti-cancer targeting strategy with simple control and practical efficacy.




These results were published in Journal of American Chemical Society (J. Am. Chem. Soc. 2014, 136, 7317?7326). One of the reviewer said: “The system of the active accumulation of the nanoparticles and the controlled release of DOX responding to light irradiation are interesting and will be promising technique for multimodal cancer treatment.”

These studies were supported by Chinese Ministry of Science and Technology, National Natural Science Foundation of China and Chinese Academy of Science.

Figure 1. Schematic illustration of the nanocomposite formulation process (A) and NIR laser induced targeting thermo-chemotherapy using the nanocomposite (B).

Figure 2. Tumor accumulation of the nanocomposite with NIR laser irradiation and synergistic thermo-chemotherapy of Dox loaded nanocomposite which effectively inhibited the growth and metastasis of tumor.

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