Characterization and Efficacy of a Nanomedical Radiopharmaceutical for Cancer Treatment.

Although much progress has been made over the last decades, there is still a significant clinical need for novel therapies to manage cancer. Typical problems are that solid tumors are frequently inaccessible, aggressive, and metastatic. To contribute to solving some of these issues, we have developed a novel radioisotope-labeled 27 nm nanoparticle, 177Lu-SN201, to selectively target solid tumors via the enhanced permeability and retention effect, allowing irradiation intratumorally. We show that 177Lu-SN201 has robust stealth properties in vitro and anti-tumor efficacy in mouse mammary gland and colon carcinoma models. The possible clinical application is also addressed with single photon emission computed tomography imaging, which confirms uptake in the tumor, with an average activity of 19.4% injected dose per gram (ID/g). The properties of 177Lu-SN201 make it a promising new agent for radionuclide therapy with the potential to target several solid tumor types.

Dosimetric Comparison of Intensity-Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Hybrid Three-Dimensional Conformal Radiotherapy/Intensity-Modulated Radiotherapy Techniques for Right Breast Cancer.

This study aimed to compare different types of right breast cancer radiotherapy planning techniques and to estimate the whole-body effective doses and the critical organ absorbed doses. The three planning techniques are intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT; two methods) and hybrid 3D-CRT/IMRT (three-dimensional conformal radiotherapy/intensity-modulated radiotherapy). The VMAT technique includes two methods to deliver a dose: non-continuous partial arc and continuous partial arc. A thermoluminescent dosimeter (TLD) is placed in the RANDO phantom to estimate the organ absorbed dose. Each planning technique applies 50.4 Gy prescription dose and treats critical organs, including the lung and heart. Dose-volume histogram was used to show the planning target volume (V95%), homogeneity index (HI), conformity index (CI), and other optimized indices. The estimation of whole-body effective dose was based on the International Commission on Radiation Protection (ICRP) Publication 60 and 103. The results were as follows: Continuous partial arc and non-continuous partial arc showed the best CI and HI. The heart absorbed doses in the continuous partial arc and hybrid 3D-CRT/IMRT were 0.07 ± 0.01% and 0% (V5% and V10%, respectively). The mean dose of the heart was lowest in hybrid 3D-CRT/IMRT (1.47 Gy ± 0.02). The dose in the left contralateral lung (V5%) was lowest in continuous partial arc (0%). The right ipsilateral lung average dose and V20% are lowest in continuous partial arc. Hybrid 3D-CRT/IMRT has the lowest mean dose to contralateral breast (organs at risk). The whole-body effective doses for ICRP-60 and ICRP-103 were highest in continuous partial arc (2.01 Sv ± 0.23 and 2.89 Sv ± 0.15, respectively). In conclusion, the use of VMAT with continuous arc has a lower risk of radiation pneumonia, while hybrid 3D-CRT/IMRT attain lower secondary malignancy risk and cardiovascular complications.

Vertical nanowire arrays as a versatile platform for protein detection and analysis.

Protein microarrays are valuable tools for protein assays. Reducing spot sizes from micro- to nano-scale facilitates miniaturization of platforms and consequently decreased material consumption, but faces inherent challenges in the reduction of fluorescent signals and compatibility with complex solutions. Here we show that vertical arrays of nanowires (NWs) can overcome several bottlenecks of using nanoarrays for extraction and analysis of proteins. The high aspect ratio of the NWs results in a large surface area available for protein immobilization and renders passivation of the surface between the NWs unnecessary. Fluorescence detection of proteins allows quantitative measurements and spatial resolution, enabling us to track individual NWs through several analytical steps, thereby allowing multiplexed detection of different proteins immobilized on different regions of the NW array. We use NW arrays for on-chip extraction, detection and functional analysis of proteins on a nano-scale platform that holds great promise for performing protein analysis on minute amounts of material. The demonstration made here on highly ordered arrays of indium arsenide (InAs) NWs is generic and can be extended to many high aspect ratio nanostructures.

Specific and reversible immobilization of histidine-tagged proteins on functionalized silicon nanowires.

Silicon nanowire (Si NW)-based field effect transistors (FETs) have shown great potential as biosensors (bioFETs) for ultra-sensitive and label-free detection of biomolecular interactions. Their sensitivity depends not only on the device properties, but also on the function of the biological recognition motif attached to the Si NWs. In this study, we show that SiNWs can be chemically functionalized with Ni:NTA motifs, suitable for the specific immobilization of proteins via a short polyhistidine tag (His-tag) at close proximity to the SiNW surface. We demonstrate that the proteins preserve their function upon immobilization onto SiNWs. Importantly, the protein immobilization on the Si NWs is shown to be reversible after addition of EDTA or imidazole, thus allowing the regeneration of the bioFET when needed, such as in the case of proteins having a limited lifetime. We anticipate that our methodology may find a generic use for the development of bioFETs exploiting functional protein assays because of its high compatibility to various types of NWs and proteins.