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.

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.

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.