Carbon Dots with Guanidinium and Amino Acid Functional Groups for Targeted Small Interfering RNA Delivery toward Tumor Gene Therapy.

Small interfering RNA (siRNA)-based gene therapy represents a promising strategy for tumor treatment. Novel gene vectors that can achieve targeted delivery of siRNA to the tumor cells without causing any side effects are urgently needed. To this end, the large amino acid mimicking carbon dots with guanidinium functionalization (LAAM GUA-CDs) are designed and synthesized by choosing arginine and dopamine hydrochloride as precursors.

Multilayer Ratiometric Fluorescent Nanomachines for Imaging mRNA in Live Cells.

Detection of mRNA expression in live cells during treatment is a challenging task, despite its importance in tumor biology and potential therapeutic leads. Here a multilayer ratiometric fluorescent nanomachine for live-cell perturbation and imaging of mRNA at single cell resolution is reported. The nanomachines fabricated by microfluidic approaches consist of fluorescent polymeric cores and multiple lipid layers, which can efficiently deliver siRNA and molecular beacons (MBs) to cytosol and then release the cargo in a sequential way.

Improving Tumor Targeting of Exosomal Membrane-Coated Polymeric Nanoparticles by Conjugation with Aptamers.

The coating of natural cellular or exosomal membranes (EMs) onto polymeric nanoparticles has become essential in extending the circulation half-time of nanoparticles by escaping from immune surveillance. Here we report on the surface modification of EM-coated poly(lactic--glycolic acid) (PLGA) nanoparticles by AS1411 aptamers (AS-EP) for improved tumor targeting. The combination of microfluidic sonication and cholesterol-modified aptamer functionalization allows for assembly of AS-EP within 10 min.

Microfluidic Sonication To Assemble Exosome Membrane-Coated Nanoparticles for Immune Evasion-Mediated Targeting.

Using natural membranes to coat nanoparticles (NPs) provides an efficient means to reduce the immune clearance of NPs and improve their tumor-specific targeting. However, fabrication of these drug-loaded biomimetic NPs, such as exosome membrane (EM)- or cancer cell membrane (CCM)-coated poly(lactic--glycolic acid) (PLGA) NPs, remains a challenging task owing to the heterogeneous nature of biomembranes and labor-intensive procedures. Herein, we report a microfluidic sonication approach to produce EM-, CCM-, and lipid-coated PLGA NPs encapsulated with imaging agents in a one-step and straightforward manner.

Low-cost thermophoretic profiling of extracellular-vesicle surface proteins for the early detection and classification of cancers.

Non-invasive assays for early cancer screening are hampered by challenges in the isolation and profiling of circulating biomarkers. Here, we show that surface proteins from serum extracellular vesicles labelled with a panel of seven fluorescent aptamers can be profiled, via thermophoretic enrichment and linear discriminant analysis, for cancer detection and classification. In a cohort of 102 patients, including 6 cancer types at stages I-IV, the assay detected stage I cancers with 95% sensitivity (95% confidence interval (CI): 74-100%) and 100% specificity (95% CI: 80-100%), and classified the cancer type with an overall accuracy of 68% (95% CI: 59-77%).

Instrument-free enrichment and detection of phosphopeptides using paper-based Phos-PAD.

The facile detection of phosphopeptides is important for clinical screening and phosphoproteomic research. This work develops an instrument-free, cost-effective, convenient paper-based method for quantitative analysis of phosphorylated peptides. With a novel portable device, Phos-PAD, this method can achieve selective enrichment and colorimetric detection of phosphopeptides within 15 min TiO nanoparticle-based chemisorption and tetrabromophenol blue-based colorimetric assay were integrated into the single paper-based analytical device.

λ-DNA- and Aptamer-Mediated Sorting and Analysis of Extracellular Vesicles.

Extracellular vesicles (EVs) are heavily implicated in diverse pathological processes. Due to their small size, distinct biogenesis, and heterogeneous marker expression, isolation and detection of single EV subpopulations are difficult. Here, we develop a λ-DNA- and aptamer-mediated approach allowing for simultaneous size-selective separation and surface protein analysis of individual EVs.

Label-free isolation of rare tumor cells from untreated whole blood by interfacial viscoelastic microfluidics.

Label-free, high-throughput, and efficient separation and enrichment of rare tumor cells, such as circulating tumor cells (CTCs), from untreated whole blood is a challenging task, owing to extremely rare events of CTCs and an enormous amount of blood cells. Current strategies for CTC separation always require pre-processing steps including lysis of blood or labeling of CTCs, leading to loss or damage of CTCs. Here, we report an interfacial viscoelastic microfluidic system for size-selective separation of tumor cells directly from whole blood, without the need of cell labeling and other treatments.