No abstract

Breast cancer (BC) is the most common malignancy in women worldwide, and one of the deadliest after lung cancer. Currently, standard methods for cancer therapy including BC are surgery followed by chemotherapy or radiotherapy. However, both chemotherapy and radiotherapy often fail to treat BC due to the side effects that these therapies incur in normal tissues and organs. In recent years, various nanoparticles (NPs) have been discovered and synthesized to be able to selectively target tumor cells without causing any harm to the healthy cells or organs. Therefore, NPs-mediated targeted drug delivery systems (DDS) have become a promising technique to treat BC. In addition to their selectivity to target tumor cells and reduce side effects, NPs have other unique properties which make them desirable for cancer treatment such as low toxicity, good compatibility, ease of preparation, high photoluminescence (PL) for bioimaging in vivo, and high loadability of drugs due to their tunable surface functionalities. In this study, we summarize with a critical analysis of the most recent therapeutic studies involving various NPs-mediated DDS as alternatives for the traditional treatment approaches for BC. It will shed light on the significance of NPs-mediated DDS and serve as a guide to seeking for the ideal methodology for future targeted drug delivery for an efficient BC treatment.

In vitro studies have proposed a tumor suppressor role for Sulfatase1 (SULF1) in hepatocellular carcinoma (HCC), however high expression in human HCC has been associated with poor prognosis. The reason underlying this paradoxical observation remains to be explored. Using a transgenic (Tg) mouse model overexpressing Sulf1 (Sulf1-Tg) we assessed the effects of SULF1 on the diethylnitrosamine (DEN) model of liver carcinogenesis. Sulf1-Tg mice show higher incidence of large and multifocal tumors with DEN injection compared to wild type (WT) mice. Lung metastases were found in 75% of Sulf1-Tg mice but not in WT mice. Immunohistochemistry (IHC), immunoblotting and reporter assays all show a significant activation of the TGFβ/SMAD transcriptional pathway by SULF1 both in vitro and in vivo. This effect of SULF1 on TGFβ/SMAD pathway is functional; overexpression of SULF1 promotes TGFβ-induced gene expression and epithelial-mesenchymal-transition (EMT), and enhances cell migration/invasiveness. Mechanistic analyses demonstrate that inactivating mutation of the catalytic site of SULF1 impairs the above actions of SULF1 and diminishes the release of TGFβ from the cell surface. And we also show that SULF1expression decreases the interaction between TGF-β1 and its HSPG sequestration receptor TGFβR3. Finally, using gene expression from human HCCs, we show that patients with high SULF1 expression have poorer recurrence-free survival (HR 4.1 (1.9–8.3); p=0.002) compared to patients with low SULF1. We also found strong correlations of SULF1 expression with TGFβ expression and with several TGFβ-related EMT genes in human HCC. CONCLUSION In summary, our study proposes a novel role of SULF1 in HCC tumor progression through augmentation of the TGFβ pathway, thus defining SULF1 as a potential biomarker for tumor progression and a novel target for drug development for HCC.

Drug delivery across the blood–brain barrier (BBB) is one of the biggest challenges in modern medicine due to the BBB’s highly semipermeable property that limits most therapeutic agents of brain diseases to enter the central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types of CDs and CD-ligand conjugates have been reported successfully penetrating the BBB, which shows a promising progress in the application of CD-based drug delivery system (DDS) for the treatment of CNS diseases. In this review, our discussion of CDs includes their classification, preparations, structures, properties, and applications for the treatment of neurodegenerative diseases, especially Alzheimer’s disease (AD) and brain tumor. Moreover, abundant functional groups on the surface, especially amine and carboxyl groups, allow CDs to conjugate with diverse drugs as versatile drug nanocarriers. In addition, structure of the BBB is briefly described, and mechanisms for transporting various molecules across the BBB and other biological barriers are elucidated. Most importantly, recent developments in drug delivery with CDs as BBB-penetrating nanodrugs and drug nanocarriers to target CNS diseases especially Alzheimer’s disease and brain tumor are summarized. Eventually, future prospects of the CD-based DDS are discussed in combination with the development of artificial intelligence and nanorobots.

A type of orange carbon dots (O-CDs) synthesized via an ultrasonication route with citric acid and 1,2-phenylenediamine as precursors was embedded into sodium polyacrylate (SPA) as the ink for 3D printing. Characterizations of these spherical O-CDs revealed an ultra-small size (~2 nm) and excitation-independent, but solvent dependent, emission. The O-CDs were evenly distributed with low degree of aggregation in sodium polyacrylate (SPA), which was achieved due to the property that SPA can absorb water together with O-CDs. The 3D printed photoluminescent objective with the ink revealed a great potential for high yield application of these materials for additive manufacturing. This also represents the first time, bare CDs have been reported as a photoluminescent material in 3D printing, as well as the first time SPA has been reported as a material for 3D printing.