Abstract

Simple SummaryMultimodal imaging systems with high registration accuracy and molecular agents with highly specific targeting capacity are vital for imaging-guided theranostics of cancer. A novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as an imaging-guided photothermal therapy (PTT) was reported in this paper. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for intrinsic simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. The highly specific imaging-guided PTT efficacy was evaluated both in vitro and in vivo. All these results suggested our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics.Multimodal imaging-guided near-infrared (NIR) photothermal therapy (PTT) is an interesting and promising cancer theranostic method. However, most of the multimodal imaging systems provide structural and functional information used for imaging guidance separately by directly combining independent imaging systems with different detectors, and many problems arise when trying to fuse different modal images that are serially taken by inviting extra markers or image fusion algorithms. Further, most imaging and therapeutic agents passively target tumors through the enhanced permeability and retention (EPR) effect, which leads to low utilization efficiency. To address these problems and systematically improve the performance of the imaging-guided PTT methodology, we report a novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as a platform for PTT-based cancer theranostics. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. In vitro and in vivo evaluation of macrophage escape and active homologous tumor targeting were performed. Cancer cell membrane-coated nanoparticles (CC-NPs) displayed excellent immune evasion ability, longer blood circulation time, and higher tumor targeting specificity compared to normal PEGylated nanoparticles, which led to highly specific upconversion luminescence (UCL) imaging and PTT-based anti-tumor efficacy. The anti-cancer efficacy of the dual-modal imaging-guided PTT was also evaluated both in vitro and in vivo. Dual-modal imaging yielded precise anatomical and functional information for the PTT process, and complete tumor ablation was achieved with CC-AuNPs. Our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics.

Highlights

  • Cancer theranostics is widely recognized as a promising strategy to precisely fight cancer [1,2,3].Among all theranostic methods, imaging-guided near-infrared (NIR) photothermal therapy (PTT)displays great advantages compared to traditional tumor ablation methods and has attracted much attention due to its minimal invasiveness to normal tissues and deep tissue penetration capacity [4,5,6,7]

  • We demonstrate that CC-AuNPs as a PTT reagent performed much better than traditionally functionalized AuNPs

  • We report a novel dual-modal imaging system based on a self-developed detector that can simultaneously record a digital radiograph and a fluorescent image without any extra registration algorithm for the fusion of these two imaging modalities

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Summary

Introduction

Cancer theranostics is widely recognized as a promising strategy to precisely fight cancer [1,2,3].Among all theranostic methods, imaging-guided near-infrared (NIR) photothermal therapy (PTT)displays great advantages compared to traditional tumor ablation methods (e.g., chemotherapy and radiotherapy) and has attracted much attention due to its minimal invasiveness to normal tissues and deep tissue penetration capacity [4,5,6,7]. Among all theranostic methods, imaging-guided near-infrared (NIR) photothermal therapy (PTT). In the past few decades, a variety of PTT reagents, including organic polymers, carbon materials, and metal nanostructures, have been developed and used for tumor ablation [7,13,14,15,16,17]. Of all of these PTT reagents, gold nanoparticles (AuNPs) with tunable localized surface plasmon resonance (LSPR) peaks located at the NIR region have been actively studied [18,19,20]. As an inert material, gold has been used in medicine for years due to its biocompatibility and non-toxicity

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