Polymer-Assisted Metallization of Mammalian Cells.

Developing biotemplating techniques to translate microorganisms and cultured mammalian cells into metallic biocomposites is of great interest for biosensors, electronics, and energy. The metallization of viruses and microbial cells is successfully demonstrated via a genetic engineering strategy or electroless deposition. However, it is difficult to transform mammalian cells into metallic biocomposites because of the complicated genes and the delicate morphological features. Herein, "polymer-assisted cell metallization" (PACM) is reported as a general method for the transformation of mammalian cells into metallic biocomposites. PACM includes a first step of in situ polymerization of functional polymer on the surface and in the interior of the mammalian cells, and a subsequent electroless deposition of metal to convert the polymer-functionalized cells into metallic biocomposites, which retain the micro- and nanostructures of the mammalian cells. This new biotemplating method is compatible with different cell types and metals to yield a wide variety of metallic biocomposites with controlled structures and properties.

Integrated remediation for organic-contaminated site by forcing running-water to modify alkali-heat/persulfate via oxidation process transfer.

As organic pollution of soil and groundwater increases, the effective and economical remediation of contaminated sites has drawn growing attention. In this study, running-water (RW) was designed to modify alkali-heat/persulfate (MAH/PS) for integrated remediation of an actual organic-contaminated site. The degradation efficiency mainly reached 60%-99% for Benz[a]anthracene, Benzo[a]pyrene and total petroleum hydrocarbons (TPHs). MAH/PS was more effective in degrading Benzene and 1,2-Dichloroethane with simple molecular configurations. The pollutant degradation efficiencies decreased with increasing site depth and increased with increasing pollutant concentrations. Migration with RW enhanced site remediation. By monitoring the groundwater after remediation, it was found that residual TPHs presented anomalous diffusion; SO42- ranged from 8.00 to 237.00 mg L-1 to 8.00-290.00 mg L-1 and pH presented alkalescence (7.00-8.20). Mathematical models were established to describe the reaction process including the solubility equilibrium of calcium hydroxide, temperature equilibrium, and reaction kinetics. Moreover, MAH/PS provided a cost-saving approach for site remediation.

Bioinspired Pollen-Like Hierarchical Surface for Efficient Recognition of Target Cancer Cells.

The efficient recognition and isolation of rare cancer cells holds great promise for cancer diagnosis and prognosis. In nature, pollens exploit spiky structures to realize recognition and adhesion to stigma. Herein, a bioinspired pollen-like hierarchical surface is developed by replicating the assembly of pollen grains, and efficient and specific recognition to target cancer cells is achieved. The pollen-like surface is fabricated by combining filtering-assisted assembly and soft lithography-based replication of pollen grains of wild chrysanthemum. After modification with a capture agent specific to cancer cells, the pollen-like surface enables the capture of target cancer cells with high efficiency and specificity. In addition, the pollen-like surface not only assures high viability of captured cells but also performs well in cell mixture system and at low cell density. This study represents a good example of constructing cell recognition biointerfaces inspired by pollen-stigma adhesion.

Unexpected high photothemal conversion efficiency of gold nanospheres upon grafting with two-photon luminescent ruthenium(II) complexes: A way towards cancer therapy?

The design and development of functional hybrid nanomaterials is currently a topic of great interest in biomedicine. Herein we investigated the grafting of Ru(II) polypyridyl complexes onto gold nanospheres (Ru@AuNPs) to improve the particles' near infrared (NIR) absorption, and ultimately allow for application in photothermal cancer therapy. As demonstrated in this article, these ruthenium(II) complexes could indeed significantly enhance gold nanospheres' two-photon luminescence (PTL) intensity and photothermal therapy (PTT) efficiency. The best dual functional nanoparticles of this study were successfully used for real-time luminescent imaging-guided PTT in live cancer cells. Furthermore, in vivo tumor ablation was achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.8 W/cm(2) for 5 min. This study demonstrates that the coupling of inert Ru(II) polypyridyl complexes to gold nanospheres allows for the enhancement of two-photon luminescence and for efficient photothermal effect.

Topographical binding to mucosa-exposed cancer cells: pollen-mimetic porous microspheres with tunable pore sizes.

Mucoadhesives have been perceived as an effective approach for targeting the mucosa-associated diseases, which relied on the adhesive molecules to enhance the specificity. Here, topographical binding is proposed based on the fabrication of surface pore size tunable pollen-mimetic microspheres with phase separation and electrospray technology. We proved that microspheres with large-pores (pore size of 1005 ± 448 nm) were the excellent potential candidate for the mucoadhesives, as they not only possessed better adhesion ability, but also could topographically bind cervical cancer cells. Our methods of topographical binding offered a new way of designing the mucoadhesives for treating the mucosa-associated diseases.

Focused ultrasound facilitated thermo-chemotherapy for targeted retinoblastoma treatment: a modeling study.

Retinoblastoma is the most common type of intraocular tumors in children. Currently, with early detection and improved systemic chemo-adjuvant therapies, treatment paradigm has shifted from survival to globe salvation/vision preservation. The objective of our work has been to explore the possible application of focused ultrasound (FUS) for targeted drug delivery in the posterior pole retinoblastoma. Specifically, theoretical models were implemented to evaluate the feasibility of using FUS to generate localized hyperthermia in retinal tumor areas, for potential triggering the chemotherapeutic agent deployment from heat-sensitive drug carriers. In-vitro experiments were conducted in tissue-mimicking phantoms with embedded excised rabbit eyes to validate the reliability of the modeling results. After confirming the reliability of our model, various FUS transducer parameters were investigated to induce maximal hyperthermia coverage in the tumor, while sparing adjacent eye structures (e.g. the lens). The evaluated FUS parameters included operating frequency, total acoustic power, geometric dimensions, transducer f-number, standoff distance, as well as different pulsing scenarios. Our modeling results suggest that the most suitable ultrasound frequency for this type of treatments was in the range of 2-3.5 MHz depending on the size of retinoblastoma. Appropriate transducer f-number (close to 1) and standoff distance could be selected to minimize the risks of over-heating undesired regions. With the total acoustic power of 0.4 W, 56.3% of the tumor was heated to hyperthermic temperature range (39-44 °C) while the temperature in lens was maintained below 41 °C. In conclusion, FUS-induced hyperthermia for targeted drug delivery may be a viable option in treatments of juxta-foveal or posterior pole retinoblastomas. Future in-vivo studies will allow us to determine the effectiveness and safety of the proposed approach.

Extracorporeal, low-energy focused ultrasound for noninvasive and nondestructive targeted hyperthermia.

The benefits of hyperthermia are well known as both a primary treatment modality and adjuvant therapy for treating cancer. Among the different techniques available, high-intensity focused ultrasound is the only noninvasive modality that can provide local hyperthermia precisely at a targeted location at any depth inside the body using image guidance. Traditionally, focused ultrasound exposures have been provided at high rates of energy deposition for thermal ablation of benign and malignant tumors. At present, exposures are being evaluated in pulsed mode, which lower the rates of energy deposition and generate primarily mechanical effects for enhancing tissue permeability to improve local drug delivery. These pulsed exposures can be modified for low-level hyperthermia as an adjuvant therapy for drug and gene delivery applications, as well as for more traditional applications such as radiosensitization. In this review, we discuss the manner by which focused ultrasound exposures at low rates of energy deposition are being developed for a variety of clinically translatable applications for the treatment of cancer. Specific preclinical studies will be highlighted. Additional information will also be provided for optimizing these exposures, including computer modeling and simulations. Various techniques for monitoring temperature elevations generated by focused ultrasound will also be reviewed.

Preliminary optimization of non-destructive high intensity focused ultrasound exposures for hyperthermia applications.

Due to its high degree of accuracy and non-invasive implementation, pulsed-high intensity focused ultrasound (HIFU) is a promising modality for hyperthermia applications as adjuvant therapy for cancer treatment. However, the relatively small focal region of the HIFU beam could result in prohibitively long treatment times for large targets requiring multiple exposures. In this work, finite element analysis modeling was used to simulate focused ultrasound propagation and the consequent induction of hyperthermia. The accuracy of the simulations was first validated with thermocouple measurements in hydrogel phantoms. More advanced simulations of in vivo applications using single HIFU exposures were then done incorporating complex, multi-layered tissue composition and variable perfusion for an in vivo murine xenograft tumor model. The results of this study describe the development of a preliminary methodology for optimizing spatial application of hyperthermia, through the evaluation of different HIFU exposures. These types of simulations, and their validations in vivo, may help minimize treatment durations for pulsed-HIFU induced hyperthermia and facilitate the translation of these exposures into the clinic.