Targeted NIRF/MR dual-mode imaging of breast cancer brain metastasis using BRBP1-functionalized ultra-small iron oxide nanoparticles

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.

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

Pharmaceutics ◽

10.3390/pharmaceutics13070995 ◽

2021 ◽

Vol 13 (7) ◽

pp. 995

Author(s):

Yucheng Peng ◽

Xiaomeng Wang ◽

Yue Wang ◽

Yue Gao ◽

Rui Guo ◽

...

Keyword(s):

Iron Oxide ◽

Mr Imaging ◽

Iron Oxide Nanoparticles ◽

Colloidal Stability ◽

Pamam Dendrimer ◽

Great Promise ◽

Oxide Nanoparticles ◽

Dual Mode ◽

Gold Nanoflowers ◽

Average Size

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.

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