Abstract

BackgroundPhotoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states.ResultsHerein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo.ConclusionsThis study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.Graphical

Highlights

  • Photoresponsive drug delivery systems open up new horizons for cancer treatments owing to their spatiotemporal control of drug accumulation in tumor tissues [1,2,3,4]

  • The self-assembled (BODIPY)3-tris(2-aminoethyl) amine (BTAEA) nanoparticles loaded with platinum (II) tetraphenyltetrabenzoporphyrin (PtTPBP) and PTX were prepared by flash nanoprecipitation method (Fig. 2a) [25, 30]

  • In this study, one-photon upconversion-like photolysis process was firstly used for red light-triggered nanoparticle disassembly and drug release

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Summary

Introduction

Photoresponsive drug delivery systems open up new horizons for cancer treatments owing to their spatiotemporal control of drug accumulation in tumor tissues [1,2,3,4] Their in vivo applications are limited by the low tissue penetration and phototoxicity of light [5, 6]. Photocleavable protecting groups (PPGs), such as borondipyrromethene (BODIPY) and cyanine, were designed to be photolyzed by long-wavelength light [11,12,13,14] They usually have large π-conjugated structures that require sophisticated synthesis, and their photolysis quantum yields are usually low. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups Such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states

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