Near Infrared-Triggered Liposome Cages for Rapid, Localized Small Molecule Delivery

Maria O Ogunyankin,Joseph A Zasadzinski,Jeong Eun Shin

doi:10.1038/s41598-020-58764-3

Maria O Ogunyankin, Joseph A Zasadzinski + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-58764-3

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Abstract

Photolabile chelating cages or protecting groups need complex chemical syntheses and require UV, visible, or two-photon NIR light to trigger release. Different cages have different solubilities, reaction rates, and energies required for triggering. Here we show that liposomes containing calcium, adenosine triphosphate, or carboxyfluorescein are tethered to plasmon-resonant hollow gold nanoshells (HGN) tuned to absorb light from 650–950 nm. Picosecond pulses of near infrared (NIR) light provided by a two-photon microscope, or by a stand-alone laser during flow through microfluidic channels, trigger contents release with spatial and temporal control. NIR light adsorption heats the HGN, inducing vapor nanobubbles that rupture the liposome, releasing cargo within milliseconds. Any water-soluble molecule can be released at essentially the same rate from the liposome-HGN. By using liposomes of different composition, or HGN of different sizes or shapes with different nanobubble threshold fluences, or irradiating on or off resonance, two different cargoes can be released simultaneously, one before the other, or in a desired ratio. Calcium release from liposome-HGN can be spatially patterned to crosslink alginate gels and trap living cells. Liposome-HGN provide stable, biocompatible isolation of the bioactive compound from its surroundings with minimal interactions with the local environment.

Highlights

Probing physiological processes requires delivering bioactive molecules such as calcium, adenosine triphosphate (ATP), and other small, water-soluble molecules with sub-micrometer spatial and millisecond temporal resolution
When the pulsed 800 nm near infrared (NIR) light is focused on the individual liposome, the liposome-hollow gold nanoshells (HGN) was ruptured and CF was released to the surrounding solution
Each bioactive molecule requires the chemical synthesis of its own “cage”; as yet, few caged compounds can combine the necessary solubility and two-photon cross section and optical efficiency to be effective under typical experimental conditions with NIR excitation

Summary

Introduction

Probing physiological processes requires delivering bioactive molecules such as calcium, adenosine triphosphate (ATP), and other small, water-soluble molecules with sub-micrometer spatial and millisecond temporal resolution. The released amount and the release rate are dependent only on the plasmonic properties of HGN, the mechanical properties of liposomes, and the wavelength and fluence of the NIR light, not on the chemical nature of the cargo.

Results

Conclusion