Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

Photothermal therapy (PTT) involves the application of normally benign light wavelengths in combination with efficient photothermal (PT) agents that convert the absorbed light to heat to ablate selected cancers. The major challenge in PTT is the ability to confine heating and thus direct cellular death to precisely where PT agents are located. The dominant strategy in the field has been to create large libraries of PT agents with increased absorption capabilities and to enhance their delivery and accumulation to achieve sufficiently high concentrations in the tissue targets of interest. While the challenge of material confinement is important for achieving “heat and lethality confinement,” this review article suggests another key prospective strategy to make this goal a reality. In this approach, equal emphasis is placed on selecting parameters of light exposure, including wavelength, duration, power density, and total power supplied, based on the intrinsic properties and geometry of tissue targets that influence heat dissipation, to truly achieve heat confinement. This review highlights significant milestones researchers have achieved, as well as examples that suggest future research directions, in this promising technique, as it becomes more relevant in clinical cancer therapy and other noncancer applications.

Supplemental Digital Content is available in the text.

For conditions with inflammatory flare-ups, fast drug-release from a depot is crucial to reduce cell infiltration and prevent long-term tissue destruction. While this concept has been explored for chronic diseases, preventing acute inflammatory flares has not been explored. To address this issue, a preventative inflammation-sensitive system is developed and applied to acute gout, a condition where millions of inflammatory cells are recruited rapidly, causing excruciating and debilitating pain. Rapid drug release is first demonstrated from a pH-responsive acetalated dextran particle loaded with dexamethasone (AcDex-DXM), reducing proinflammatory cytokines in vitro as efficiently as free drug. Then, using the air pouch model of gout, mice are pretreated 24 h before inducing inflammation. AcDex-DXM reduces overall cell infiltration with decreased neutrophils, increases monocytes, and diminishes cytokines and chemokines. In a more extended prophylaxis model, murine joints are pretreated eight days before initiating inflammation. After quantifying cell infiltration, only AcDex-DXM reduces the overall joint inflammation, where neither free drug nor a conventional drug-depot achieves adequate anti-inflammatory effects. Here, the superior efficacy of disease-triggered drug-delivery to prevent acute inflammation is demonstrated over free drug and slow-release depots. This approach and results promise exciting treatment opportunities for multiple inflammatory conditions suffering from acute flares.