Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine

Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to their translation. Successful clinical translation of these nanoparticles is heavily dependent on their stability, circulation time, access and bioavailability to disease sites, and their safety profile. This review covers preclinical and clinical inorganic-nanoparticle based nanomaterial utilized for cancer imaging and therapeutics. A special emphasis is put on the rational design to develop non-toxic/safe inorganic nanoparticle constructs to increase their viability as translatable nanomedicine for cancer therapies

Light-Driven Polymeric Bilayer Actuators Fabricated by 3-D Printing

4D printing is an emerging additive manufacturing technology that combines the precision of 3D printing with the versatility of smart materials. 4D printed objects can change their shape over time with the application of a stimulus (i.e., heat, light, moisture). Light driven smart materials are attractive because light is wireless, remote, and can induce a rapid shape change. Herein, we present a method for fabricating polymeric bilayer actuators via 3D printing which reversibly change their shape upon exposure to light. The photoactive layer consists of a poly(siloxane) containing pendant azobenzene groups. Several different photoactive polymers were synthesized, to study how substitution of the benzene rings affected the properties of the active layer polymers and the bilayer actuators. The photomechanical effect displayed by the bilayers was evaluated quantitatively. These bilayers exhibit rapid actuation with full cycles completed within seconds, and photo-generated stresses ranging from 1.03 - 1.70 MPa.Ph.D., Chemistry -- Drexel University, 201

Photoactivated Polymeric Bilayer Actuators Fabricated via 3D Printing

4D printing is an emerging additive manufacturing technology that combines the precision of 3D printing with the versatility of smart materials. 4D printed objects can change their shape over time with the application of a stimulus (i.e., heat, light, moisture). Light driven smart materials are attractive because light is wireless, remote, and can induce a rapid shape change. Herein, we present a method for fabricating polymeric bilayer actuators via 3D printing which reversibly change their shape upon exposure to light. The photoactive layer consists of a poly­(siloxane) containing pendant azobenzene groups. Two different photoactive polymers were synthesized, and the photomechanical effect displayed by the bilayers was evaluated. These bilayers exhibit rapid actuation with full cycles completed within seconds, and photo generated stresses ranging from 1.03 to 1.70 MPa

Photoactivated Polymeric Bilayer Actuators Fabricated via 3D Printing

4D printing is an emerging additive manufacturing technology that combines the precision of 3D printing with the versatility of smart materials. 4D printed objects can change their shape over time with the application of a stimulus (i.e., heat, light, moisture). Light driven smart materials are attractive because light is wireless, remote, and can induce a rapid shape change. Herein, we present a method for fabricating polymeric bilayer actuators via 3D printing which reversibly change their shape upon exposure to light. The photoactive layer consists of a poly­(siloxane) containing pendant azobenzene groups. Two different photoactive polymers were synthesized, and the photomechanical effect displayed by the bilayers was evaluated. These bilayers exhibit rapid actuation with full cycles completed within seconds, and photo generated stresses ranging from 1.03 to 1.70 MPa

Photoactivated Polymeric Bilayer Actuators Fabricated via 3D Printing

4D printing is an emerging additive manufacturing technology that combines the precision of 3D printing with the versatility of smart materials. 4D printed objects can change their shape over time with the application of a stimulus (i.e., heat, light, moisture). Light driven smart materials are attractive because light is wireless, remote, and can induce a rapid shape change. Herein, we present a method for fabricating polymeric bilayer actuators via 3D printing which reversibly change their shape upon exposure to light. The photoactive layer consists of a poly­(siloxane) containing pendant azobenzene groups. Two different photoactive polymers were synthesized, and the photomechanical effect displayed by the bilayers was evaluated. These bilayers exhibit rapid actuation with full cycles completed within seconds, and photo generated stresses ranging from 1.03 to 1.70 MPa

Recent Advances in Nanomedicine for the Diagnosis and Treatment of Prostate Cancer Bone Metastasis

Patients with advanced prostate cancer can develop painful and debilitating bone metastases. Currently available interventions for prostate cancer bone metastases, including chemotherapy, bisphosphonates, and radiopharmaceuticals, are only palliative. They can relieve pain, reduce complications (e.g., bone fractures), and improve quality of life, but they do not significantly improve survival times. Therefore, additional strategies to enhance the diagnosis and treatment of prostate cancer bone metastases are needed. Nanotechnology is a versatile platform that has been used to increase the specificity and therapeutic efficacy of various treatments for prostate cancer bone metastases. In this review, we summarize preclinical research that utilizes nanotechnology to develop novel diagnostic imaging tools, translational models, and therapies to combat prostate cancer bone metastases

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on $10^3$ pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype