Progress of nanomaterials in the treatment of thrombus.

Thrombus has long been the major contributor of death and disability because it can cause adverse effects to varying degrees on the body, resulting in vascular blockage, embolism, heart valve deformation, widespread bleeding, etc. However, clinically, conventional thrombolytic drug treatments have hemorrhagic complication risks and easy to miss the best time of treatment window. Thus, it is an urgent need to investigate newly alternative treatment strategies that can reduce adverse effects and improve treatment effectiveness. Drugs based on nanomaterials act as a new biomedical strategy and promising tools, and have already been investigated for both diagnostic and therapeutic purposes in thrombus therapy. Recent studies have some encouraging progress. In the present review, we primarily concern with the latest developments in the areas of nanomedicines targeting thrombosis therapy. We present the thrombus' formation, characteristics, and biomarkers for diagnosis, overview recent emerging nanomedicine strategies for thrombus therapy, and focus on the future design directions, challenges, and prospects in the nanomedicine application in thrombus therapy.

Photothermal Nanoheaters-Modified Spores for Safe and Controllable Antitumor Therapy.

Introduction: To present a safer tumor therapy based on bacteria and identify in detail how the activation and infection behavior of spores can be controlled remotely by near-infrared light (NIR-irradiation) based on nanoheaters' modification. Methods: Spores bring a better tolerance to surface modification. Transitive gold-nanorods-allied-nanoclusters-modified spores (Spore@NRs/NCs) were constructed by covalent glutaraldehyde crosslink. The photothermal properties of nanoheaters before and after attachment to spores were studied by recording temperature-irradiation time curves. The controlled viability and infection behavior of Spore@NRs/NCs were investigated by NIR-irradiation. Results: In this work, a controllable sterilizing effect to activated vegetative bacteria was obtained obviously. When met with a suitable growth-environment, Spore@NRs/NCs could germinate, activate into vegetative bacteria and continue to reproduce. Without NIR-irradiation, nanoheaters could not affect the activity of both spores and vegetative bacterial cells. However, with NIR-irradiation after incubating in growth medium, nanoheaters on spores could control the spores' germination and affect the growth curve as well as the viability of the vegetative bacterial cells. For Spore@NRs/NCs (Spore:NCs:NRs=1:1:4, 67.5 µg mL-1), a ~98% killing rate of vegetative bacterial cells was obtained with NIR-irradiation (2.8 W cm-2, 20 min) after 2 h-incubation. In addition, these nanoheaters modified on spores could be taken not only to the vegetative bacteria cells, but also to the first-generation bacteria cells with their excellent photothermal and bactericidal performance, as well as synergetic anticancer effect. NIR-irradiation after 2 h-incubation could also trigger Spore@NRs/NCs (1:1:4, 6 µL) to synergistically reduce the viability of HCT116 cells to 15.63±2.90%. Conclusion: By using NIR-irradiation, the "transitive" nanoheaters can remotely control the activity of both bacteria (germinated from spore) and cancer cells. This discovery provides basis and a feasible plan for controllable safer treatment of bacteria therapy, especially anaerobes with spores in hypoxic areas of the malignant solid tumors.

NIR-responsive sandwich drug loading system for tumor targeting and multiple combined treatment.

A novel drug loading system, Au@Si-NN-Si@SiO2, is constructed by a layer-by-layer assembly approach. The core Au nanorods serve as the matrix for a near-infrared light (NIR) responsive photothermal feature. Meanwhile, the assembly's middle shell is composed of azobenzene linked silica, which produces free radicals by breaking -NN- bonds at a high temperature brought about by a NIR irradiation-caused photothermal effect, which further triggers the loaded drug release. The outer shell is formed of SiO2 in order to prevent leakage of drug in the middle layer. The fully drug loaded nanocarriers, Au@Si-NN-Si@SiO2-Dox, exhibit an excellent photothermal effect (43%) at a concentration of 170 µg mL-1 under 808 nm NIR laser at 2.3 W cm-2. The antitumor performance of Au@Si-NN-Si@SiO2-Dox was investigated using human colon cancer cells (HCT116) as a model. By combining NIR-triggered drug release, free radical generation and the photothermal effect, the proposed Au@Si-NN-Si@SiO2-Dox exhibits improved antitumor efficiency. By using a dosage of 170 µg mL-1, a cell viability of 17.56% is achieved for HCT116 (5 × 103-1 × 104 cells per well) with 10 min of NIR laser irradiation (808 nm, 2.3 W cm-2). All the results demonstrate that Au@Si-NN-Si@SiO2-Dox exhibits wonderful dosage-dependent antitumor performance and has great potential as a therapeutic agent for tumors or even for use in the clinic.

ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules.

Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated. In the present study, we aimed to investigate the influence of ST3Gal III on key steps in the process of breast cancer metastasis. ST3Gal III-overexpressing and ST3Gal III-silenced breast cancer MDA-MB-231 cell lines were generated. They showed an increase or decrease in the tumor-associated antigen sialyl-Lewis X (SLeX). The E-selectin binding capacity of the transfectants was proportional to cell surface SLeX levels. Cell migration and invasion were positively correlated with ST3Gal III levels. Moreover, ST3Gal III expression modulated the protein expression of invasion-related molecules, including ß1 integrin, matrix metalloproteinase (MMP)-2, MMP-9 and cyclooxygenase-2, which may account for the mechanism involved in the effects of ST3Gal III on breast cancer invasiveness. In conclusion, our findings in these novel models of ST3Gal III expression revealed a critical requirement for ST3Gal III in several steps of breast cancer metastasis. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. This study provides novel insights into the mechanisms underlying metastasis and suggests a new target for the effective drug treatment of breast cancer metastasis.