Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Abstract

Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65–80% and 20–35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.

Macrophage Membrane-Coated Nano-Gemcitabine Promotes Lymphocyte Infiltration and Synergizes AntiPD-L1 to Restore the Tumoricidal Function

“…Moreover, a previous report has revealed that the nanoparticles that arrived at the tumor sites could be partially internalized by various cell components. 45 As a result, the red fluorescence signals in tumors could be attributed to the fluorescence dyes that were encapsulated in and released from the nanovehicles, which could be used to characterize their distribution profiles in tumor tissues.…”

Pore-engineered nanoarchitectonics for cancer therapy

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Nanoprobe-based molecular imaging for tumor stratification

“…82 The aim of quantifying the distribution of nanoparticles inside/outside tumor cells was also demonstrated through a pH/light dual-response monochromatic ratiometric imaging nanoparticle (MRIN). 83 The fluorescence signal of MRIN remained in the ''OFF'' state, while the signal from Cy5 was switched ''ON'' as MRIN dissociated in the lysosome. The intracellular and extracellular Cy5 fluorescence signals were illuminated and the fluorescence signal from Cy5 of the extracellularly distributed nanoparticles was quantified via an 808 nm laser to photodegrade Cy7.5.…”