Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer

Triple-negative breast cancer(TNBC)is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed,and human epidermal growth factor receptor 2 is not amplified or overexpressed either,which make the clinical diagnosis and treatment very challenging.Molecular imaging can provide an effective way to diagnose TNBC.Upconversion nanoparticles(UCNPs),are a promising new generation of molecular imaging probes.However,UCNPs still need to be improved for tumor-targeting ability and biocompatibility.This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles(CCm-UCNPs),owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes,and modified multifunctional UCNPs.This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo.By using this probe,MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo.Based on the tumor imaging and molecular classification results,the probe is also expected to be modified for drug delivery in the future,contributing to the treatment of TNBC.The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury

Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanoparticles(PCurNP)are designed to meet the renal excretion threshold(~45 kDa),presenting a controllable delivery nanosystem for kidney targeting.Renal accumulation of the relatively small nanoparticles,^(89)Zr-PCurNP M10 with the diameter between 5 and 8 nm,is found to be 1.7 times and 1.8 times higher than the accumulation of^(89)Zr-PCurNP M29(20-50 nm)and M40(20-50 nm)as revealed by PET imaging.Furthermore,serum creatinine analysis,kidney tissues histology,and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI.Herein,PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

^(18)F-FDG PET/CT在新型冠状病毒肺炎诊断中的应用

新型冠状病毒肺炎(COVID-19)被发现以来,迅速蔓延,其早期诊断有利于患者的及时救治和疾病进一步传播的有效控制。目前,诊断的依据是流行病史、临床表现、影像学特征和逆转录聚合酶链式反应(RT-PCR)检测结果,其中RT-PCR检测到新型冠状病毒核酸阳性是COVID-19确诊的主要依据,影像学特征尤其是肺部高分辨率CT表现则是诊断该病的重要临床依据。作为一种被广泛应用的影像学方法,^(18)F-FDG PET/CT在COVID-19中的价值仍未可知。笔者分析了^(18)F-FDG PET/CT在COVID-19中的诊断和鉴别诊断的价值,以及评估COVID-19患者纵隔淋巴结受累情况方面的潜在应用,讨论了COVID-19患者肺外器官和组织受累可能出现的^(18)F-FDG PET/CT影像学表现。

Efficient renal clearance of DNA tetrahedron nanopartides enables quantitative evaluation of kidney function

DNA tetrahedro n nano structure (DTN) is one of the simplest DNA nano structures and has bee n successfully applied for biose nsin g, imagi ng, and treatment of can cer. To facilitate its biomedical applications and pote ntial clinical tran slation, fun dame ntal un derstandi ng of DTN's transportation among major organs in living organisms becomes increasingly important. Here, we describe the efficient renal clearanee of DTN in healthy mice by using positron emission tomography (PET) imaging. The kidney elimination of DTN was later applied for renal function evaluation in murine models of unilateral ureteral obstruction (UUO). We further established a mathematical program of DTN to validate its changes of transportation pattern in healthy and UUO mice. We believe the establishment of pharmacokinetic profiles and mathematical model of DTN may provide in sight for future optimization of DNA nano structures for biomedical applications.

General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

Multifunctional yolk/shell-structured hybrid nanomaterials have attracted increasing interest as theranostic nanoplatforms for cancer imaging and therapy. However, because of the lack of suitable surface engineering and tumor targeting strategies, previous research has focused mainly on nanostructure design and synthesis with few successful examples showing active tumor targeting after systemic administration. In this study, we report the general synthetic strategy of chelator-free zirconium-89 （89Zr）-radiolabeled, TRC105 antibody-conjugated, silica-based yolk/sheU hybrid nanopartides for in vivo tumor vasculature targeting. Three types of inorganic nanoparticles with varying morphologies and sizes were selected as the internal cores, which were encapsulated into single hollow mesoporous silica nanosheUs to form the yolk/sheU-structured hybrid nanopartides. As a proof-of-concept, we demonstrated successful surface functionalization of the nanoparticles with polyethylene glycol, TRC105 antibody （specific for CD105/endoglin）, and ~Zr （a positron-emitting radioisotope）, and enhanced in vivo tumor vasculature-targeted positron emission tomography imaging in 4T1 murine breast tumor-bearing mice. This strategy could be applied to the synthesis of other types of yolk/shell theranostic nanoparticles for tumor- targeted imaging and drug delivery.

Spherical nucleic acids:Organized nucleotide aggregates as versatile nanomedicine

Spherical nucleic acids(SNAs)are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells.After the first report of SNA by Mirkin and coworkers in 1996,it has created a significant interest by offering new possibilities in the field of gene and drug delivery.The controlled aggregation of oligonucleotides on the surface of organic/inorganic nanoparticles improves the delivery of genes and nucleic acid–based drugs and alters and regulates the biological profiles of the nanoparticle core within living organisms.Here in this review,we present an overview of the recent progress of SNAs that has speeded up their biomedical application and their potential transition to clinical use.We start with introducing the concept and characteristics of SNAs as drug/gene delivery systems and highlight recent efforts of bioengineering SNA by imaging and treatmenting various diseases.Finally,we discuss potential challenges and opportunities of SNAs,their ongoing clinical trials,and future translation,and how they may affect the current landscape of clinical practices.We hope that this review will update our current understanding of SNA,organized oligonucleotide aggregates,for disease diagnosis and treatment.