Macrophage-Laden Gold Nanoflowers Embedded with Ultrasmall Iron Oxide Nanoparticles for Enhanced Dual-Mode CT/MR Imaging of Tumors.

Yucheng Peng,Yue Gao,Xiangyang Shi,Yue Wang,Xiaomeng Wang,Xueyan Cao,Rui Guo

doi:10.3390/pharmaceutics13070995

Yucheng Peng, Yue Gao + Show 5 more

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https://doi.org/10.3390/pharmaceutics13070995

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Abstract

The design of multimodal imaging nanoplatforms with improved tumor accumulation represents a major trend in the current development of precision nanomedicine. To this end, we report herein the preparation of macrophage (MA)-laden gold nanoflowers (NFs) embedded with ultrasmall iron oxide nanoparticles (USIO NPs) for enhanced dual-mode computed tomography (CT) and magnetic resonance (MR) imaging of tumors. In this work, generation 5 poly(amidoamine) (G5 PAMAM) dendrimer-stabilized gold (Au) NPs were conjugated with sodium citrate-stabilized USIO NPs to form hybrid seed particles for the subsequent growth of Au nanoflowers (NFs). Afterwards, the remaining terminal amines of dendrimers were acetylated to form the dendrimer-stabilized Fe3O4/Au NFs (for short, Fe3O4/Au DSNFs). The acquired Fe3O4/Au DSNFs possess an average size around 90 nm, display a high r1 relaxivity (1.22 mM−1 s−1), and exhibit good colloidal stability and cytocompatibility. The created hybrid DSNFs can be loaded within MAs without producing any toxicity to the cells. Through the mediation of MAs with a tumor homing and immune evasion property, the Fe3O4/Au DSNFs can be delivered to tumors more efficiently than those without MAs after intravenous injection, thus significantly improving the MR/CT imaging performance of tumors. The developed MA-mediated delivery system may hold great promise for enhanced tumor delivery of other contrast agents or nanomedicines for precision cancer nanomedicine applications.

Highlights

Molecular imaging techniques, based on various functional nanoparticles, have attracted increasing attention in the recent development of cancer nanomedicine which is critical for early tumor therapy guidance [1]
The development of nanoplatforms integrated with different imaging techniques such as computed tomography (CT)[2], ultrasound (US) [3], photoacoustic (PA) [4], and magnetic resonance (MR) [5] imaging represent a competitive strategy for precision cancer diagnoses
The carboxyl groups of Ultrasmall iron oxide (USIO) NPs were activated with ethylcarbodiimide hydrochloride (EDC), the activated USIO NPs were added dropwise into the solution of Au DSNPs with amino groups on the surface, and the Fe3 O4 /Au DSNPs was generated through covalent bonding

Summary

Introduction

Molecular imaging techniques, based on various functional nanoparticles, have attracted increasing attention in the recent development of cancer nanomedicine which is critical for early tumor therapy guidance [1]. The development of nanoplatforms integrated with different imaging techniques such as computed tomography (CT)[2], ultrasound (US) [3], photoacoustic (PA) [4], and magnetic resonance (MR) [5] imaging represent a competitive strategy for precision cancer diagnoses. Au NPs have been broadly used in CT technology and PTT (photothermal therapy) attributing to their intrinsic advantages of an excellent X-ray attenuation feature as well as a near-infrared (NIR) absorption property, respectively [7]. In order to realize the precision molecular imaging, it was desirable to incorporate both.

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