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Materials

Nanoparticle Middlemen Could Help Release Drugs Deep Into Tissue

Drug Delivery: Gel embedded with lanthanide nanoparticles dumps protein drugs when particles absorb near-infrared light

by Elizabeth K. Wilson
October 3, 2012

Released By Light
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Credit: J. Am. Chem. Soc.
Near-infrared light (red squiggle, left) penetrates a photosensitive hydrogel, hitting lanthanide nanoparticles (green circles). The nanoparticles release ultraviolet light (purple squiggles), which then triggers photoresponsive chemical groups in the polymer backbones (red triangles) to cleave the polymer chains (black curves). Through this chemical reaction, the photoresponsive groups change into another type of chemical group. When the gel comes apart, proteins or other biomolecules (yellow) escape.
20121003lnj1-hydrogel.jpg
Credit: J. Am. Chem. Soc.
Near-infrared light (red squiggle, left) penetrates a photosensitive hydrogel, hitting lanthanide nanoparticles (green circles). The nanoparticles release ultraviolet light (purple squiggles), which then triggers photoresponsive chemical groups in the polymer backbones (red triangles) to cleave the polymer chains (black curves). Through this chemical reaction, the photoresponsive groups change into another type of chemical group. When the gel comes apart, proteins or other biomolecules (yellow) escape.

A new hydrogel containing lanthanide-based nanoparticles releases proteins when hit with near-infrared light (J. Am. Chem. Soc., DOI: 10.1021/ja308876j). The nanoparticle-studded gel could enable doctors to cue the release of protein drugs deep inside a patient’s tissues, the developers say.

Other researchers have designed and tested photosensitive hydrogels, which consist of polymers that encapsulate proteins or small-molecule drugs. High-energy ultraviolet light can break the polymers’ bonds and release the gel’s payload. But researchers would rather use near-infrared light because it is safer and can penetrate deeper into tissue than UV light can.

Yue Zhao of the University of Sherbrooke, in Quebec, Neil R. Branda, at Simon Fraser University, in British Columbia, and their colleagues developed an approach to make hydrogels responsive to near-IR light. They impregnated a hydrogel with lanthanide-doped nanoparticles, composed of a NaYF4 core doped with thulium and ytterbium, and wrapped with a NaYF4 shell. These nanoparticles have an unusual property: When bombarded by two or more low-energy photons, such as those from near-IR light, the particles can spit out photons of shorter wavelengths, such as UV light. The process is called upconversion.

Zhao and Branda’s hydrogel is a cross-linked web of polyacrylamide and polyethylene glycol, held together by photoresponsive o-nitrobenzyl groups. When exposed to near-IR light, the nanoparticles emit UV light, which then triggers the nitrobenzyl groups to cleave the polymer chains. When the polymers come apart, the gel’s contents spill out.

The team tested their gel by filling it with a fluorescently labeled protein. They placed a 12-mm-wide piece of gel in buffer and monitored the buffer’s fluorescence as they shined near-IR light on the gel. After about 50 minutes of irradiation, almost 70% of the protein escaped from the gel.

The authors note that this nanoparticle technology could work with other biocompatible hydrogels.

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