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Posted: Apr 27th, 2009
Photo-triggered on demand drug release of nanoparticles
(Nanowerk Spotlight) A number of applications in nanomedicine – imaging, drug delivery or photo therapy for instance – utilize phenomena called two-photon absorption (TPA). In TPA, the simultaneous absorption of two photons excite a molecule from one state to a higher energy electronic state. TPA initially was used only as a spectroscopic tool but new applications emerged over time.
"Currently approved two-photon absorption-induced excitation is one of the most promising approaches in photo therapies as it increases light penetration," Dong-Hwang Chen tells Nanowerk."It enables the use of light in the tissue-transparent window (750–1000 nm), allowing deeper light penetration and reduced risk of laser hyperthermia. An uphill energy conversion through the use of two-photon absorbing chromophores and subsequent energy transfer is a promising scientific frontier."
Chen, a Distinguished Professor in the Department of Chemical Engineering at National Cheng Kung University in Tainan, Taiwan, continues to explain that fluorescence resonant energy transfer (FRET)-based semiconductor nanocrystal sensors and nanoformulation for photodynamic therapy have emerged over the past few years as promising nanoscales for analyte detection and light-activated treatment for cancer and other diseases.
Drug release triggered by two-photon excitation in near infrared (NIR) using the FRET technique have not yet been developed despite much progress in photo-triggered drug release.
"One of the promising approaches to obtain large intrinsic two-photon absorption cross sections in the near-infrared region is to exploit the energy-transferring combination of existing photosensitive linkers with two-photon absorption dyes," he says. "Here, the photosensitive linker (energy acceptor) is indirectly excited through fluorescence resonance energy from the two-photon absorption dye unit (energy donor)."
This previous work has motivated Chen and his group to design a new class of drug nanocarriers capable of on demand drug release by efficient up-converting energy of NIR light to higher energy and intraparticle energy transfer for drug release.
The result is a multifunctional nanoparticle that can efficiently absorb the energy of NIR light and emit light of higher energy for triggering drug release by cleavage of a photosensitive linker.
Photo-triggered release of Dexa by up-converting energy of NIR light to higher energy and indirect energy transfer from RDB grafted gum arabic bound Fe3O4 nanoparticle to the linker. (Reprinted with permission from IOP Publishing)
Chen points out that, although the use of a fluorophore to cleave a linker molecule has been reported, in all the cases UV light has been utilized to cleave the linker. "The concept of energy harvesting by uphill energy conversions through the use of two-photon absorption and the phenomenon of FRET has never been utilized."
This approach involves an energy-transferring magnetic nanoscopic co-assembly fabricated of rhodamine B fluorescent dye grafted gum arabic modified Fe3O4 magnetic nanoparticle (GAMNP) and photosensitive linker by which dexamethasone (a corticosteroid drug that acts as an anti-inflammatory and immunosuppressant and is used in cancer therapies of brain tumors) is conjugated to the magnetic nano-assembly.
One issue that the researchers found with their nanocarrier is that rhodamine, which acts as energy acceptor, showed slow degradation on prolong exposure to NIR. But they are confident that this problem can be resolved by using semiconductor nanocrystals in place of fluorescent dyes like rhodamine B.
Generally, this kind of multifunctional nanocarriers will provide targeted and on demand drug release that will lead to more effective therapies, eliminating the potential for both under and overdosing; the need for fewer administrations; optimal use of the drug in question; and increased patient compliance.
These nanocarriers will revolutionize especially cancer chemotherapies. Most chemotherapeutic compounds are nonspecific and are taken up by all types of cells – and this nonselective nature of the agents usually causes severe toxicity. The drug nanocarriers currently under development will dramatically improve the treatment of cancer by selectively providing the optimum dosage of the drug at the tumor site, ultimately even the individual tumor cell.
According to Chen, the type of nanocarrier designed by his group provides several advantages such as
"1) magnetic guiding to the desired target area and fixing them at the local site while the medication is released and acts locally;
2) surface functionalization by gum arabic provides an opportunity to allow directing the therapeutic agent to selected cells away from other cells and, in doing so, provides a method for targeting a therapeutic agent into selected cells;
3) the combined properties of fluorescence and magnetism associated with nanoparticles offer new opportunities for in vitro and in vivo imaging; and
4) indirect photo-triggering-on-demand drug release by efficient up-converting energy of the near-IR (NIR) light to higher energy and intraparticle energy transfer from the dye-grafted magnetic nanoparticle to the linker for photo-cleavage."
The approach of two-photon induced intraparticles FRET for drug release, based on the use of two-photon fluorescent nanoassembly as a donor and a photosensitive linker as an acceptor, offers a novel design for developing formulations of smart drug-carrier nanoassemblies for more superior control over the location and the onset of drug release.