SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

22

Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria-enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor-targeting S. Typhimurium VNP20009 are interfaced with poly(lactic-co-glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self-replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria’s intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100-fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.

20

Multiphoton microscopy of cellular autofluorescence and second harmonic generation from collagen facilitates imaging of living cells and tissues without the need for additional fluorescent labels. Here, a compact multiphoton endomicroscope for label-free in vivo imaging in small animals via side-viewing needle objectives is presented. Minimal invasive imaging at cellular resolution is performed in colonoscopy of mice without surgical measures and without fluorescent dyes as a contrast agent. The colon mucosa is imaged repeatedly in the same animal in a mouse model of acute intestinal inflammation to study the process of inflammation at the tissue level within a time period of ten days, demonstrating the capabilities of label-free endomicroscopy for longitudinal studies for the first time.

19

Utilizing the intrinsic mobility-strain relationship in semiconductors is critical for enabling strain engineering applications in high-performance flexible electronics. Here, measurements of Hall effect and Raman spectra of an organic semiconductor as a function of uniaxial mechanical strain are reported. This study reveals a very strong, anisotropic, and reversible modulation of the intrinsic (trap-free) charge carrier mobility of single-crystal rubrene transistors with strain, showing that the effective mobility of organic circuits can be enhanced by up to 100% with only 1% of compressive strain. Consistently, Raman spectroscopy reveals a systematic shift of the low-frequency Raman modes of rubrene to higher (lower) frequencies with compressive (tensile) strain, which is indicative of a reduction (enhancement) of thermal molecular disorder in the crystal with strain. This study lays the foundation of the strain engineering in organic electronics and advances the knowledge of the relationship between the carrier mobility, low-frequency vibrational modes, strain, and molecular disorder in organic semiconductors.

19

Submucosal elevation, the process of instilling material in the submucosal space for separation of the surface mucosa and deeper muscularis layer, is a significant aspect of the endoscopic mucosal resection of large lesions performed to facilitate lesion removal and maximize safety. Submucosal injection, when applied, has historically been performed with normal saline, though this is limited by its rapid dissipation; solutions ideally need to be easily injectable, biocompatible, and provide a long-lasting submucosal cushion with a desirable height. Here, reported is a new set of materials, endoscopically injectable shear-thinning hydrogels, meeting these requirements because of their biocompatible components and ability to form a solid hydrogel upon injection. These findings are supported by evaluation in a large animal model and ultimately demonstrate the potential of these shear-thinning hydrogels to serve as efficient submucosal injection fluids for cushion development. Given these unique characteristics, their broad application in mucosal resection techniques is anticipated.

18

Ultrasound-based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer’s disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham-controlled clinical studies.

18

Pressure (P), temperature (T), and humidity (H) are physical key parameters of great relevance for various applications such as in distributed diagnostics, robotics, electronic skins, functional clothing, and many other Internet-of-Things (IoT) solutions. Previous studies on monitoring and recording these three parameters have focused on the integration of three individual single-parameter sensors into an electronic circuit, also comprising dedicated sense amplifiers, signal processing, and communication interfaces. To limit complexity in, e.g., multifunctional IoT systems, and thus reducing the manufacturing costs of such sensing/communication outposts, it is desirable to achieve one single-sensor device that simultaneously or consecutively measures P-T-H without cross-talks in the sensing functionality. Herein, a novel organic mixed ion-electron conducting aerogel is reported, which can sense P-T-H with minimal cross-talk between the measured parameters. The exclusive read-out of the three individual parameters is performed electronically in one single device configuration and is enabled by the use of a novel strategy that combines electronic and ionic Seebeck effect along with mixed ion-electron conduction in an elastic aerogel. The findings promise for multipurpose IoT technology with reduced complexity and production costs, features that are highly anticipated in distributed diagnostics, monitoring, safety, and security applications.

16

Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44-targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.

15

Bacterial inclusion bodies (IBs) are mechanically stable protein particles in the microscale, which behave as robust, slow-protein-releasing amyloids. Upon exposure to cultured cells or upon subcutaneous or intratumor injection, these protein materials secrete functional IB polypeptides, functionally mimicking the endocrine release of peptide hormones from secretory amyloid granules. Being appealing as delivery systems for prolonged protein drug release, the development of IBs toward clinical applications is, however, severely constrained by their bacterial origin and by the undefined and protein-to-protein, batch-to-batch variable composition. In this context, the de novo fabrication of artificial IBs (ArtIBs) by simple, cell-free physicochemical methods, using pure components at defined amounts is proposed here. By this, the resulting functional protein microparticles are intriguing, chemically defined biomimetic materials that replicate relevant functionalities of natural IBs, including mammalian cell penetration and local or remote release of functional ArtIB-forming protein. In default of severe regulatory issues, the concept of ArtIBs is proposed as a novel exploitable category of biomaterials for biotechnological and biomedical applications, resulting from simple fabrication and envisaging soft developmental routes to clinics.

15

Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their ability to accumulate at high densities into many cancer types, including, breast, prostate, brain, and colon cancer. Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture. The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered. Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells. Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor. Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a. As macrophages are heavily involved in tumor progression, understanding how to use macrophages for drug delivery can substantially benefit the treatment of tumors.

15

Clean operating margins in breast cancer surgery are important for preventing recurrence. However, the current methods for determining margins such as intraoperative frozen section analysis or imprint cytology are not satisfactory since they are time-consuming and cause a burden on the patient and on hospitals with a limited accuracy. A “click-to-sense” probe is developed based on the detection of acrolein, which is a substance released by oxidatively stressed cancer cells and can be visualized under fluorescence microscopy. Using live breast tissues resected from breast cancer patients, it is demonstrated that this method can quickly, selectively, and sensitively differentiate cancer lesion from normal breast gland or benign proliferative lesions. Since acrolein is accumulated in all types of cancers, this method could be used to quickly assess the surgical margins in other types of cancer.