Lang Rao

Cancer Cell Membrane-Coated Upconversion Nanoprobes for Highly Specific Tumor Imaging.

Cancer cell membrane-coated upconversion nanoprobes (CC-UCNPs) with immune escape and homologous targeting capabilities are used for highly specific tumor imaging. The combination of UCNPs with biomimetic cancer cell membranes embodies a novel materials design strategy and presents a compelling class of advanced materials.

Microfluidic Electroporation-Facilitated Synthesis of Erythrocyte Membrane-Coated Magnetic Nanoparticles for Enhanced Imaging-Guided Cancer Therapy

Biomimetic cell membrane-coated nanoparticles (CM-NPs) with superior biochemical properties have been broadly utilized for various biomedical applications. Currently, researchers primarily focus on using ultrasonic treatment and mechanical extrusion to improve the synthesis of CM-NPs. In this work, we demonstrate that microfluidic electroporation can effectively facilitate the synthesis of CM-NPs. To test it, Fe3O4 magnetic nanoparticles (MNs) and red blood cell membrane-derived vesicles (RBC-vesicles) are infused into a microfluidic device. When the mixture of MNs and RBC-vesicles flow through the electroporation zone, the electric pulses can effectively promote the entry of MNs into RBC-vesicles. After that, the resulting RBC membrane-capped MNs (RBC-MNs) are collected from the chip and injected into experimental animals to test the in vivo performance. Owing to the superior magnetic and photothermal properties of the MN cores and the long blood circulation characteristic of the RBC membrane shells, core-shell RBC-MNs were used for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Due to the completer cell membrane coating, RBC-MNs prepared by microfluidic electroporation strategy exhibit significantly better treatment effect than the one fabricated by conventional extrusion. We believe the combination of microfluidic electroporation and CM-NPs provides an insight into the synthesis of bioinpired nanoparticles to improve cancer diagnosis and therapy.

Capture and release of cancer cells using electrospun etchable MnO2 nanofibers integrated in microchannels

This paper introduces a cancer cell capture/release microchip based on the self-sacrificed MnO2 nanofibers. Through electrospinning, lift-off and soft-lithography procedures, MnO2 nanofibers are tactfully fabricated in microchannels to implement enrichment and release of cancer cells in liquid samples. The MnO2 nanofiber net which mimics the extra cellular matrix can lead to high capture ability with the help of a cancer cell-specific antibody bio-conjugation. Subsequently, an effective and friendly release method is carried out by using low concentration of oxalic acid to dissolve the MnO2 nanofiber substrate while keeping high viability of those released cancer cells at the same time. It is conceivable that our microchip may have potentials in realizing biomedical analysis of circulating tumor cells for biological and clinical researches in oncology.

Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated.

Effective cancer targeting and imaging using macrophage membrane‐camouflaged upconversion nanoparticles

Upconversion nanoparticles (UCNPs), with fascinating optical and chemical features, are a promising new generation of fluorescent probes. Although UCNPs have been widely used in diagnosis and therapy, there is an unmet need for a simple and effective surface engineering method that can produce cancer-targeting UCNPs. Here, we show that by coating particles with macrophage membranes, it becomes possible to utilize the adhesion between macrophages and cancer cells for effective cancer targeting. Natural macrophage membranes along with their associated membrane proteins were reconstructed into vesicles and then coated onto synthetic UCNPs. The resulting macrophage membrane-camouflaged particles (MM-UCNPs) exhibited effective cancer targeting capability inherited from the source cells and were further used for enhanced in vivo cancer imaging. Finally, the blood biochemistry, hematology testing and histology analysis results suggested a good in vivo biocompatibility of MM-UCNPs. The combination of synthetic nanoparticles with biomimetic cell membranes embodies a novel design strategy toward developing biocompatible nanoprobes for potential clinical applications.

Autofluorescent gelatin nanoparticles as imaging probes to monitor matrix metalloproteinase metabolism of cancer cells.

In this paper, autofluorescent gelatin nanoparticles were synthesized as matrix metalloproteinase (MMP) responsive probes for cancer cell imaging. A modified two-step desolvation method was employed to generate these nanoparticles whose size was controllable and had stable autofluorescence. As glutaraldehyde was introduced as the crosslinking agent, the generation of Schiff base (CN) and double carbon bond (CC) between glutaraldehyde and gelatin endowed these gelatin nanoparticles distinct autofluorescence. Considering MMPs were usually overexpressed on the surface of cancer cells and they had degradation ability toward gelatin, we utilized these nanoparticles as imaging probes to responsively monitor the MMP metabolism of cancer cells according to the luminance change. As fluorescent probes, these nanoparticles had facile synthesis procedure and good biocompatibility, and provided a smart strategy to monitor cancer cell behaviors.

Efficient Purification and Release of Circulating Tumor Cells by Synergistic Effect of Biomarker and SiO2@Gel‐Microbead‐Based Size Difference Amplification

Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead-binding selectively enlarges target cell size, providing efficient high-purity capture. CTCs captured can be further released non-invasively. This stratagem enables high-performance CTC isolation for subsequent studies.

One-step fabrication of 3D silver paste electrodes into microfluidic devices for enhanced droplet-based cell sorting

3D microelectrodes are one-step fabricated into a microfluidic droplet separator by filling conductive silver paste into PDMS microchambers. The advantages of 3D silver paste electrodes in promoting droplet sorting accuracy are systematically demonstrated by theoretical calculation, numerical simulation and experimental validation. The employment of 3D electrodes also helps to decrease the droplet sorting voltage, guaranteeing that cells encapsulated in droplets undergo chip-based sorting processes are at better metabolic status for further potential cellular assays. At last, target droplet containing single cell are selectively sorted out from others by an appropriate electric pulse. This method provides a simple and inexpensive alternative to fabricate 3D electrodes, and it is expected our 3D electrode-integrated microfluidic droplet separator platform can be widely used in single cell operation and analysis.

Platelet‐Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Here, we present a platelet-facilitated photothermal tumor therapy (PLT-PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR-loaded PLTs (PLT-AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene-knockout mouse model, we demonstrate that the administration of PLT-AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT-AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self-reinforcing characteristic of PLT-PTT in cancer therapy.

Fetal nucleated red blood cell analysis for non-invasive prenatal diagnostics using a nanostructure microchip

Cell-free DNA has been widely used in non-invasive prenatal diagnostics (NIPD) nowadays. Compared to these incomplete and multi-source DNA fragments, fetal nucleated red blood cells (fNRBCs), once as an aided biomarker to monitor potential fetal pathological conditions, have re-attracted research interest in NIPD because of their definite fetal source and the total genetic information contained in the nuclei. Isolating these fetal cells from maternal peripheral blood and subsequent cell-based bio-analysis make maximal genetic diagnosis possible, while causing minimal harm to the fetus or its mother. In this paper, an affinity microchip is reported which uses hydroxyapatite/chitosan nanoparticles as well as immuno-agent anti-CD147 to effectively isolate fNRBCs from maternal peripheral blood, and on-chip biomedical analysis was demonstrated as a proof of concept for NIPD based on fNRBCs. Tens of fNRBCs can be isolated from 1 mL of peripheral blood (almost 25 mL-1 in average) from normal pregnant women (from the 10th to 30th gestational week). The diagnostic application of fNRBCs for fetal chromosome disorders (Trisomy 13 and 21) was also demonstrated. Our method offers effective isolation and accurate analysis of fNRBCs to implement comprehensive NIPD and to enhance insights into fetal cell development.