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Reactive oxygen species (ROS) generation to induce cell death is an effective strategy for cancer therapy. In particular, chemodynamic therapy (CDT), using Fenton-type reactions to generate highly cytotoxic hydroxyl radical (•OH), is a promising treatment modality. However, the therapeutic efficacy of ROS-based cancer treatment is still limited by some critical challenges, such as overexpression of enzymatic and non-enzymatic antioxidants by tumor cells, as well as the low tumor targeting efficiency of therapeutic agents. To address those problems, biomimetic CuZn protoporphyrin IX nanoscale coordination polymers have been developed, which significantly amplify oxidative stress against tumors by simultaneously inhibiting enzymatic and non-enzymatic antioxidants and initiating the CDT. In this design, cancer cell membrane camouflaged nanoparticle exhibits an excellent homotypic targeting effect. After being endocytosed into tumor cells, the nanoparticles induce depletion of the main non-enzymatic antioxidant glutathione (GSH) by undergoing a redox reaction with GSH. Afterward, the redox reaction generated cuprous ion (Cu

Extracellular vesicles (EVs) are lipid-bilayer-enclosed vesicles with sub-micrometer size that are released by various cells. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Growing evidence has shown important biological roles and clinical relevance of EVs in diseases. For EV-related studies to thrive, rapid efficient isolation of pure EVs is a prerequisite. However, lengthy procedure, low yield, low throughput, and high contaminants stemmed from existing isolation approaches hamper both basic research and large-scale clinical implementation. We have shown that lipid nanoprobes (LNP) enable spontaneous labeling and rapid isolation of EVs by coupling with magnetic enrichment. Recently, we further developed a one-step EV isolation platform that utilizes EV size-matched silica nanostructures and surface-conjugated LNPs with an integrated microfluidic mixer. EVs, derived from up to 2-ml clinical plasma, can be processed with this point-of-care device using optimized flow rate. Subsequently, contents of isolated EVs can be extracted on-chip and eluted from the device for downstream molecular analyses. The LNP-functionalized microfluidic device combined with state-of-the-art analysis platforms could have great potential in promoting EV-centered research and clinical use in the future.

Vertically aligned carbon nanotubes (VACNTs), a unique classification of CNT, highly oriented and normal to the respective substrate, have been heavily researched over the last two decades. Unlike randomly oriented CNT, VACNTs have demonstrated numerous advantages making it an extremely desirable nanomaterial for many biomedical applications. These advantages include better spatial uniformity, increased surface area, greater susceptibility to functionalization, improved electrocatalytic activity, faster electron transfer, higher resolution in sensing, and more. This Review discusses VACNT and its utilization in biomedical applications particularly for sensing, biomolecule filtration systems, cell stimulation, regenerative medicine, drug delivery, and bacteria inhibition. Furthermore, comparisons are made between VACNT and its traditionally nonaligned, randomly oriented counterpart. Thus, we aim to provide a better understanding of VACNT and its potential applications within the community and encourage its utilization in the future.

Nanoscale extracellular vesicles (nEVs) have recently demonstrated potential value in cancer diagnostics and treatment monitoring, but translation has been limited by technical challenges in nEV isolation. Thus, we have developed a one-step nEV isolation platform that utilizes nEV size-matched silica nanostructures and a surface-conjugated lipid nanoprobe with an integrated microfluidic mixer. The reported platform has 28.8% capture efficiency from pancreatic cancer plasma and can sufficiently enrich nEVs for simpler positive identification of point mutations, particularly KRAS, in nEV DNA from the plasma of pancreatic cancer patients.

Extracellular vesicles (EVs), from clinical plasma samples, have recently been used towards applications of cancer diagnostics and treatment monitoring. However, clinical translation has been limited by technical challenges in EV enrichment. Thus, we have reported on the development of a microdevice platform that utilizes dual capture principles for improved EV isolation and enrichment. By utilizing (1) an EV-specific lipid nanoprobe-grafted silica for isolation via EV tethering and (2) EV size-matched nanostructures for isolation via physical trapping, isolation efficiency is increased by nearly three times. Furthermore, this continuous-flow microdevice eliminates plasma protein contaminants by upwards of ~97%.

Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. Recently, they have been demonstrated for potential value in cancer diagnostics and treatment monitoring. However, relevant clinical translation is mainly limited by technical challenges in EV isolation. We previously reported lipid nanoprobes, which is a nanomaterial system of labeling probe and capture probe. The labeling probe is constructed with a lipid molecule as the active component to label EVs rapidly and spontaneously with high efficiency, while the capture probe can isolate labeled EVs magnetically. Herein, we report on the development of a microfluidic device with integrated lipid nanoprobe for on-chip EV isolation towards instrument development for clinical translation. The nanostructured substrate of the device is integrated with a micromixer for one-step isolation of EVs from 1-ml plasma. We validated the device with plasma collected from pancreatic cancer patients, followed by DNA mutation detection of EV cargo. Size-tunable nanostructures are fabricated by patterning high-resolution iron thin films on fused silica substrates. By judicious thermal annealing, homogeneously dispersed iron nanoparticles are formed by fission and fusion on the substrate, which are served as a mask for silica dry-etching. Subsequently, selected lipid nanoprobes, which can instantaneously insert into lipid bilayers of EVs, are grafted onto the nanostructured substrate in a micromixer. This platform is verified first to isolate cultured cancer cell-derived EVs spiked-in plasma samples that emulated clinical samples. This platform is further applied to isolate EVs from pancreatic cancer patients’ plasma and identified KRASmutations in EV DNA with highly sensitive droplet digital PCR. Together, this platform enables rapid and efficient isolation of EVs from plasma specimens, and thus, holds great potential in clinical translation. Citation Format: Siyang Zheng, Yuan Wan, Mackenzie Maurer, Yi-Qiu Xia, Si-Jie Hao, Wen-Long Zhang, Nelson S. Yee. Microfluidic device integrated with lipid nanoprobe for extracellular vesicle isolation toward non-invasive cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2437.