Abstract

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.

Highlights

  • Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer

  • Strategies aimed at exogenously imposed specific regulation over the location and duration of the immune response remain a central theme in the field of cancer immunotherapy[6,7]

  • When the quencher (BHQ2)-bearing PcDNA (Q-PcDNA) hybridizes to the Cy3-labeled CpG (Cy3-CpG), energy transfer occurred from Cy3 to the quencher because of their proximity, from which the photoactivation process was evaluated (Fig. 2a, b)

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Summary

Introduction

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. We present the construction of a NIR light-activated immunodevice for remote and noninvasive control of the timing and location of immunotherapeutic functions in vivo with reduced systemic toxicity. This methodology uses photon upconversion nanotechnology to achieve intended control of NIR light which is much more desirable than UV or visible light because it allows deeper tissue penetration with less photodamage. UCNPs, capable of converting low-energy NIR incident photons into high-energy UV light locally, function as a transducer for the remote control over the cleavage of the PC bond and achieve activation of the PCpG in the NIR window, where deep tissue penetration and remote activation are feasible. Since such upconversion efficiency is orders of magnitude greater than that of multiphoton processes, a low power continuous-wave (CW) NIR laser diode is sufficient to yield strong upconversion luminescence (UCL) by UCNPs34

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