Multitasking nanoparticles target cancer
Nanomedicine
March 4, 2008
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| Transmission electron micrographs of uncoated PLGA NPs containing the chemotherapeutic drug DOXO and superparamagnetic Fe3O4 nanocrystals. (Credit: Jaeyun Kim, Seoul National University.) |
Considerable efforts are being directed toward developing multifunctional nanomedicines. Researchers from the Korea Advanced Institute of Science and Technology and Seoul National University have developed polymer nanoparticles (NPs) that act as multimodal imaging probes and use magnetic guidance to improve drug delivery [Kim et al., Adv. Mater. (2008) 20, 478].
The platform comprises four key components: (i) biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) NPs (100–200 nm in diameter) as the polymer matrix; (ii) hydrophobic, inorganic nanocrystals embedded into the matrix, either superparamagnetic Fe3O4 nanocrystals (15 nm diameter) for MRI contrast and magnetically guided drug delivery or CdSe/ZnS semiconductor quantum dots (3 nm in diameter) for optical imaging; (iii) the chemotherapeutic drug doxorubicin (DOXO) incorporated into the polymer matrix in NP form; and (iv) finally, cancer-targeting folate conjugated onto the modified PLGA NPs via polyethylene glycol (PEG) groups.
MRI and fluorescence imaging tests were performed on untreated cancer cells over-expressing folate receptors and cells mixed with either folate-free or folate-coated functionalized PLGA (containing Fe3O4 or CdSe/ZnS, as appropriate).
Both techniques detected cancer cells treated with the NPs, with the best results achieved for folate-coated particles. When an external magnetic field is applied, the sensitivity of MRI to the cancer cells increases even further.
Fluorescence observations confirm that CdSe/ZnS-impregnated NPs
can deliver a chemotherapeutic payload into target cells. Confocal
laser scanning microscopy and flow cytometry similarly confirm cellular
uptake of the Fe3O4-containing NPs. As expected, uptake of these particles
is improved when an external magnetic field is applied.
In vivo studies are now planned to test whether the fully functionalized NPs can, indeed, be used to image tumor volumes and target drug delivery in the presence of an external magnetic field.
Taeghwan Hyeon of Seoul National University is optimistic. “We expect the NPs will accumulate at the tumor site, allowing the tumor to be detected and destroyed at the same time,” he says.
Paula Gould