Sensitive and Specific Detection of Breast Cancer Lymph Node Metastasis Through Dual-Modality Magnetic Particle Imaging and Fluorescence Molecular Imaging: a Preclinical Evaluation

Purpose: A sensitive and specific imaging method to detect metastatic cancer cells in lymph nodes (LNs) to detect the early-stage breast cancer is urgently needed. The purpose of this study was to investigate a novel breast cancer-targeting and tumour microenvironment ATP-responsive superparamagnetic iron oxide (SPIOs) imaging probe that was developed to detect lymph node metastasis (LNMs) through fluorescence molecular imaging (FMI) and magnetic particle imaging (MPI). The imaging nanoprobe comprised of SPIOs conjugated with breast cancer-targeting peptides (CREKA) and an ATP-responsive DNA aptamer (dsDNA-Cy5.5), abbreviated as SPIOs@A-T. Methods: SPIOs@A-T was synthesised and characterized for its imaging properties, targeting ability and toxicity in vitro. Mice with metastatic lymph node (MLN) of breast cancer were established to evaluate the FMI and MPI imaging strategy in vivo. Healthy mice with normal lymph node (NLN) were used as control group. Histological examination and biosafety evaluation were performed for further assessment. Results: After injection with SPIO@A-T, the obvious high fluorescent intensity and MPI signal were observed in MLN group than those in NLN group. MPI could also complement the limitation of imaging depth from FMI, thus could detect MLN more sensitively. The combination of the imaging strengths of FMI and MPI ensured the detection of breast cancer metastases with high sensitivity and specificity, thereby facilitating the precision differentiation of malignant from benign LNs. Besides, the biosafety evaluation results showed SPIO@A-T had good biocompatibility. Conclusion: Due to the superior properties of tumour-targeting, detection specificity, and biosafety, the SPIOs@A-T imaging probe in combination with FMI and MPI can provide a promising novel method for the early and precise detection of LNMs in clinical practice.

A Novel Insight Into Mechanism of Derangement of Coagulation Balance: Interactions of Quantum Dots with Coagulation-Related Proteins

Background Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven’t been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins. Results QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolytic systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM>PLG>FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes. Conclusions The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level.

Biosafety Evaluation and Quantitative Determination of Poly(hexamethylene biguanide) (PHMB) Coated on Cellulosic Fabrics by Kubelka-Munk Equation

It is a challenge to determine the quantity of cationic finishing agents on the surface of cellulosic fabrics. Herein, we report a direct and feasible method by Kubelka-Munk equation to quantify the cationic poly (hexamethylene biguanide) hydrochloride (PHMB) adsorbed onto cotton fabrics based on the principle of formation of a stable blue dye between PHMB and bromophenol blue sodium (BPB). The adsorption of PHMB onto cotton fabrics was first investigated and the maximum adsorption of PHMB was found to be around 8 mg per gram of cotton fabric. After being dyed with BPB, colour strength shows a positive correlation with PHMB at low concentrations (< 2400 mg/L). A linear relationship with a high correlation (C(PHMB) = (K/S—0.7411)/3.4517, R2 = 0.9983) was thus established between colour strength and PHMB concentration. However, this equation should fulfill four requirements for quantifying PHMB: (1) the distribution of PHMB on the surface of cellulosic fabric should be in the form of a monolayer with the content less than 5.3 mg/g; (2) an excess of BPB dyebath should be applied; (3) the dyeing should come to equilibrium; and (4) the fabrics should be evenly dyed. Moreover, MTT assay results indicate that excess PHMB coated on cotton fabrics can cause cytotoxicity and the quantity of PHMB should not exceed 4.62 mg per gram of cotton fabrics for the purpose of biosafety. The sample can be considered non-cytotoxic if the K/S value is lower than 13.2 after dyeing with BPB.