In vivo gastrointestinal drug-release monitoring through second near-infrared window fluorescent bioimaging with orally delivered microcarriers

Rui Wang,Xiaomin Li,Lei Zhou,Fan Zhang,Wenxing Wang

doi:10.1038/ncomms14702

Abstract

Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance. Here, we report a novel microcarrier that can retain drugs and withstand the harsh conditions of gastrointestinal tract. Significantly, we can track the microcarrier fate and semi-quantitatively monitor the content of drug released in vivo in real time by measuring the fluorescence signals in the second near-infrared window of lanthanide-based downconversion nanoparticles with an absorption competition-induced emission bioimaging system. The microcarriers show a prolonged residence time of up to 72 h in the gastrointestinal tract, releasing up to 62% of their content. Moreover, minimal deposition of the microcarriers is found in non-target organs, such as the liver, spleen and kidney. These findings provide novel insights for the development of therapeutic and bioimaging strategies of orally administered drugs.

Highlights

Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance
We report a novel type of downconversion nanoparticles (DCNPs)-based NIR-II fluorescent mesoporous microcarrier for orally delivering protein drugs
NaGdF4:5%Nd@NaGdF4 DCNPs were prepared by a successive layer-by-layer (SLBL) strategy[35,36]

Summary

Introduction

Non-invasive monitoring of gastrointestinal drug release in vivo is extremely challenging because of the limited spatial resolution and long scanning time of existing bioimaging modalities, such as X-ray radiation and magnetic resonance. We can track the microcarrier fate and semi-quantitatively monitor the content of drug released in vivo in real time by measuring the fluorescence signals in the second near-infrared window of lanthanide-based downconversion nanoparticles with an absorption competition-induced emission bioimaging system. Most of the fluorophores emit only in the visible range (400–750 nm) and first near-infrared (NIR-I) window (750–900 nm) with a low tissue penetration depth of several micrometres to millimetres because of the severe absorption and scattering of photons by tissues[23,24] Fluorescent agents such as quantum dots (QDs)[25,26], single-walled carbon nanotubes (SWNTs)[27,28] and lanthanidebased downconversion nanoparticles (DCNPs)[23,29] emitting in the second near-infrared (NIR-II) window (1,000–1,400 nm) have been widely reported. The activity of the released enzymes from the orally delivered microcarriers was largely preserved, further indicating the feasibility of using microcarriers for oral drug delivery

Methods

Results

Conclusion