An iron oxide nanoparticle-based transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors.

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption. STATEMENT OF SIGNIFICANCE: Transdermal delivery is an attractive strategy for treating superficial tumors. However, a highly efficient transdermal nanoplatform remains to be developed. Herein, we designed a multifunctional transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, comprised of a super-paramagnetic iron oxide (SPIO) nanoparticle, which can act as an MRI contrast agent and photothermal agent; a transdermal enhanced peptide (TD) and cationic lipids, which can accelerate skin penetration; and a NIR dye (DiR) and doxorubicin (DOX), which can achieve a synergistic enhanced chemo-photothermal therapy with NIR imaging ability. The transdermal nanoplatform achieved efficient tumor eradication and low systemic toxicity, thus offering strong potential for clinical adoption.

A Transparent Vessel-on-a-Chip Device for Hemodynamic Analysis and Early Diagnosis of Intracranial Aneurysms by CFD and PC-MRI.

Hemodynamics plays a critical role in early diagnosis and investigating the growth mechanism of intracranial aneurysms (IAs), which usually induce hemorrhagic stroke, serious neurological diseases, and even death. We developed a transparent blood vessel-on-a-chip (VOC) device for magnetic resonance imaging (MRI) to provide characteristic flow fields of early IAs as the reference for early diagnosis. This VOC device takes advantage of the transparent property to clearly exhibit the internal structure and identify the needless air bubbles in the biomimetic fluid experiment, which significantly affects the MRI image quality. Furthermore, the device was miniaturized and easily assembled with arbitrary direction using a 3D-printed scaffold in a radiofrequency coil. Computational fluid dynamics (CFD) simulations of the flow field were greatly consistent with those data from MRI. Both internal flow and wall shear stress (WSS) exhibited very low levels during the IA growth, thus leading to the growth and rupture of IAs. PC-MRI images can also provide a reasonable basis for the early diagnosis of IAs. Therefore, we believed that this proposed VOC-based MR imaging technique has great potential for early diagnostic of intracranial aneurysms.

Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy.

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM-1 s-1), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.

Integrin αvß3 Receptor Overexpressing on Tumor-Targeted Positive MRI-Guided Chemotherapy.

Multifunctional nanomaterials with targeted imaging and chemotherapy have high demand with great challenge. Herein, we rationally aimed to design multifunctional drug delivery systems by RGD-modified chitosan (CH)-coated nanoneedles (NDs) of gadolinium arsenate (RGD-CH-Gd-AsNDs). These NDs have multifunctionality for imaging and targeted therapy. NDs on intravenous administration demonstrated significant accumulation of As ions/species in tumor tissues, which was monitored by the change in T1-weighted magnetic resonance (MR) imaging. Moreover, NDs were well opsonized in cells with high specificity, subsequently inducing apoptosis to the HepG2 cells. Consequent to this, the in vivo results demonstrated biosafety, enhanced tumor targeting, and tumor regression in a subcutaneously transplanted xenograft model in nude mice. These RGD-CH-Gd-AsNDs have great potential, and we anticipate that they could serve as a novel platform for real-time T1-weighted MR diagnosis and chemotherapy.

"Magnus nano-bullets" as T1/T2 based dual-modal for in vitro and in vivo MRI visualization.

Tissue specific T1/T2 dual contrast abilities for magnetic resonance imaging (MRI) have great significance in initial detection of cancer lesions. Herein, we developed a novel kind of Magnus nano-bullets (Mn-DTPA-F-MSNs) distinguished by magnetic (Fe3O4-NPs) head combined with mesoporous (SiO2) persist body, respectively. Subsequently, modify mesoporous SiO2 group and finally loaded with Mn2+. These Magnus nano-bullets have relaxivity value (r1 = 5.12 mM-1 s-1) and relaxivity value (r2 = 265.32 mM-1 s-1); they were > 2 folds in comparison to control at 3.0 T. Meanwhile, Magnus nano-bullets also offered significant enhancements for the detection of Glutathione (GSH), a biomarker that has been showed a redox responsive T1-weighted MRI effect in vitro and in vivo evaluations with good biocompatibility. Therefore, our finding endorses that Magnus nano-bullets offer a "smart" and tremendous strategy for greater GSH responsive T1/T2 dual MRI image probes for future biomedical applications.

A multi-slot coaxial microwave antenna for liver tumor ablation.

This paper presents a multi-slot coaxial antenna with a pi impedance matching network for liver tumor ablation. A multi-slot radiating probe was optimized by using the modified genetic algorithm to produce a near-spherical heating zone with significantly increased possibility of conformal treatment. A pi impedance matching network was designed to match the feeding transmission line and antenna without increasing antenna size. The reflection coefficient, ablation zone shape, specific absorption rate, and temperature were determined by a finite element electromagnetic simulation using COMSOL. Experimental validations were designed to evaluate the proposed antenna. Both simulation and experimental results show that the proposed antenna has the ability for liver tumor ablation, which offers faster heating rates in the heating center and more localized heating distribution than the conventional single-slot antenna.

Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents.

T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM(-1) s(-1) and an r2 value of 186.51 mM(-1) s(-1), which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.