Aim Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia. Method Novel gold nanorod elastin-like polypeptide matrices were generated and characterized. The matrices were also loaded with the heat-shock protein (HSP)90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), currently in clinical trials for different malignancies, in order to deliver a combination of hyperthermia and chemotherapy. Results Laser irradiation of cells cultured over the plasmonic matrices (without 17-AAG) resulted in the death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of prosurvival HSPs, reduce the efficacy of hyperthermia treatment. 17-AAG–gold nanorod–polypeptide matrices demonstrated minimal leaching of the drug to surrounding media. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant (>90%) death of cancer cells, while ‘single treatments’ (i.e., hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability (<10%). Conclusion Simultaneous administration of hyperthermia and HSP inhibitor release from plasmonic matrices is a powerful approach for the ablation of malignant cells and can be extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies.
Herein, we introduce a simple route to fabricating hydrophilic microfluidic chips with an alternative material, a UV‐cured polyurethane‐related polymer, known as Norland Optical Adhesive (NOA 63). Conventionally, polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic chips as an alternative to glass or SiO2 because PDMS is easily molded and relatively cheap. However, despite these advantages, the hydrophobicity of PDMS entails critical problems when it is used in microfluidic chips because microchannels inside the microfluidic chips, which have extremely low surface tension, are difficult to fill with aqueous solution without an extra pumping system. To overcome these problems, significant efforts have been focused on developing procedures to change the PDMS surface to be hydrophilic. However, the resulting hydrophilicity is generally short‐lived and the modification procedures require cumbersome multi‐steps. In the present study, we demonstrate that microchannel‐molding and microfluidic chip construction are easier using NOA 63 than when using PDMS and that the hydrophilicity of the NOA surface, which is induced by treatment with O2 plasma, lasts longer, for at least one month. Due to the longer lasting hydrophilicity, microchannels in NOA 63 microfluidic chips are spontaneously filled with solution by capillary reaction without any extra pumping over the period. The feasibility of NOA 63‐based microfabrication is verified by demonstrating NOA 63 microfluidic platforms with antibody‐immobilized beads for immunoassays.
A new microfluidic valve or a "v-type valve" which can be flexibly actuated to focus a fluid flow and block a specific area of a microchannel is demonstrated. Valves with different design parameters were fabricated by multilayer soft lithography and characterized at various operating pressures. To evaluate the functionality of the valve, single microparticles (∅ 7 μm and ∅ 15 μm) and single cells were trapped from flowing suspensions. Continuous processes of particle capture and release were achieved by controlling the actuation and deactuation of the valve. Integration of the v-type valve with poly(dimethyl siloxane) (PDMS) monolithic valves in microfluidic devices was demonstrated to illustrate the potential of the system in various applications such as the creation of a solid phase column, the isolation of a specific number of particles in reactors, and the capture and release of particles or cells in the flow of two immiscible liquids. We believe that this new valve system will be suitable for manipulating particles and cells in a broad range of applications.
In this study, we introduce a microfluidic device equipped with pneumatically actuated valves, generating a linear gradient of chemoeffectors to quantify the chemotactic response of Tetrahymena pyriformis, a freshwater ciliate. The microfluidic device was fabricated from an elastomer, poly(dimethylsiloxane) (PDMS), using multi-layer soft lithography. The components of the device include electronically controlled pneumatic microvalves, microchannels and microchambers. The linear gradient of the chemoeffectors was established by releasing a chemical from a ciliate-free microchamber into a microchamber containing the ciliate. The ciliate showed chemotactic behaviours by either swimming toward or avoiding the gradient. By counting the number of ciliates residing in each microchamber, we obtained a precise time-response curve. The ciliates in the microfluidic device were sensitive enough to be attracted to 10 pmol glycine-proline, which indicates a 10(5) increase in the ciliate's known sensitivity. With the use of blockers, such as DL-2-amino-5-phosphonopentanoic acid (APPA) or lanthanum chloride (LaCl3), we have demonstrated that the NMDA (N-methyl-d-aspartate) receptor plays a critical role in the perception of chemoeffectors, whereas the Ca2+ channel is related to the motility of the ciliate. These results demonstrate that our microfluidic chemotaxis assay system is useful not only for the study of ciliate chemotaxis but also for a better understanding of the signal transduction mechanism on their receptors.
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