Non-destructive neurotransmitter detection and real-time monitoring of stem cell differentiation are both of great significance in the field of neurodegenerative disease and regenerative medicine.Although luminescent biosensing nanoprobes have been developed to address this need, they have intrinsic limitations such as autofluorescence, scattering, and phototoxicity. However, upconversion nanoparticles (UCNPs) have gained increasing attention for various biomedical applications due to their high photo-stability, low auto-fluorescent background, and deep tissue penetration; however, UCNPs also suffer from low emission intensities due to undesirable energy migration pathways. To

In this study, we report the use of a multifunctional magnetic core-shell nanoparticle (MCNP), composed of a highly magnetic zinc-doped iron oxide (ZnFeO) core nanoparticle and a biocompatible mesoporous silica (mSi) shell, for the simultaneous delivery of let-7a microRNA (miRNA) and anticancer drugs (e.g., doxorubicin) to overcome chemoresistance in breast cancer. Owing to the ability of let-7a to repress DNA repair mechanisms (e.g., BRCA1 and BRCA2) and downregulate drug efflux pumps (e.g., ABCG2), delivery of let-7a could sensitize chemoresistant breast cancer cells (MDA-MB-231) to subsequent doxorubicin chemotherapy both in vitro and in vivo. Moreover, the multifunctionality of our MCNPs allows for the monitoring of in vivo delivery via magnetic resonance imaging. In short, we have developed a multifunctional MCNP-based therapeutic approach to provide an attractive method with which to enhance our ability not only to deliver combined miRNA therapeutics with small-molecule drugs in both selective and effective manner but also to sensitize cancer cells for the enhanced treatment via the combination of miRNA replacement therapy using a single nanoplatform.

In the present study, we fabricated magnetic oleosomes functionalized with recombinant proteins as a new carrier for oil-based lipophilic drugs for cancer treatment. The bioengineered oleosome is composed of neutral lipids surrounded by a phospholipid monolayer with embedded oleosin fusion proteins. The oleosin was genetically fused to a nanobody of a green fluorescent protein (GFP). A recombinant protein consisting of immunoglobulin-binding protein LG fused to GFP was used to couple the oleosome to an antibody for targeted delivery to breast cancer cells. The lipid core of the oleosome was loaded with magnetic nanoparticles and carmustine as the lipophilic drug. The magnetic oleosome was characterized using transmission electron microscopy and dynamic light scattering. Moreover, the specific delivery of oleosome into the target cancer cell was investigated via confocal microscopy. To examine the cell viability of the delivered oleosome, a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out. Furthermore, an animal study was conducted to confirm the effect resulting from the delivery of the anticancer drug-loaded oleosomes. Taken together, the fabricated lipophilic drug-loaded magnetic oleosome can be a powerful tool for oil-based drug delivery agent for cancer therapy.

Light-mediated remote control of stem cell fate, such as proliferation, differentiation, and migration, can bring a significant impact on stem cell biology and regenerative medicine. Current UV/vis-mediated control approaches are limited in terms of nonspecific absorption, poor tissue penetration, and phototoxicity. Upconversion nanoparticle (UCNP)-based near-infrared (NIR)-mediated control systems have gained increasing attention for vast applications with minimal nonspecific absorption, good penetration depth, and minimal phototoxicity from NIR excitations. Specifically, 808 nm NIR-responsive upconversion nanomaterials have shown clear advantages for biomedical applications owing to diminished heating effects and better tissue penetration. Herein, a novel 808 nm NIR-mediated control method for stem cell differentiation has been developed using multishell UCNPs, which are optimized for upconverting 808 nm NIR light to UV emission. The locally generated UV emissions further toggle photoswitching polymer capping ligands to achieve spatiotemporally controlled small-molecule release. More specifically, with 808 nm NIR excitation, stem cell differentiation factors can be released to guide neural stem cell (NSC) differentiation in a highly controlled manner. Given the challenges in stem cell behavior control, the developed 808 nm NIR-responsive UCNP-based approach to control stem cell differentiation can represent a new tool for studying single-molecule roles in stem cell and developmental biology.

Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors. Sodium nitroprusside (SNP) and diethyldithiocarbamate (DDC) were selected as an exogenous reactive oxygen species (ROS) generator and a superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple cancer cell lines effectively by the generation of peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate tumor cells (breast cancer cells) via magnetic hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating iRGD peptide moieties in the THoR-NP, integrin-enriched cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective cancer therapy.