Artificial intelligence (AI) and nanotechnology are two fields that are instrumental in realizing the goal of precision medicine—tailoring the best treatment for each cancer patient. Recent ...conversion between these two fields is enabling better patient data acquisition and improved design of nanomaterials for precision cancer medicine. Diagnostic nanomaterials are used to assemble a patient‐specific disease profile, which is then leveraged, through a set of therapeutic nanotechnologies, to improve the treatment outcome. However, high intratumor and interpatient heterogeneities make the rational design of diagnostic and therapeutic platforms, and analysis of their output, extremely difficult. Integration of AI approaches can bridge this gap, using pattern analysis and classification algorithms for improved diagnostic and therapeutic accuracy. Nanomedicine design also benefits from the application of AI, by optimizing material properties according to predicted interactions with the target drug, biological fluids, immune system, vasculature, and cell membranes, all affecting therapeutic efficacy. Here, fundamental concepts in AI are described and the contributions and promise of nanotechnology coupled with AI to the future of precision cancer medicine are reviewed.
Artificial intelligence (AI) and nanotechnology are instrumental in realizing the goal of precision medicine—tailoring the best treatment for each cancer patient. Recent conversion between these fields is enabling better patient data acquisition and improved design of nanomaterials. Fundamental concepts in AI and the contributions of nanotechnology and AI to the future of precision cancer medicine are reviewed.
Development of regulated cellular processes and signaling methods in synthetic cells is essential for their integration with living materials. Light is an attractive tool to achieve this, but the ...limited penetration depth into tissue of visible light restricts its usability for in-vivo applications. Here, we describe the design and implementation of bioluminescent intercellular and intracellular signaling mechanisms in synthetic cells, dismissing the need for an external light source. First, we engineer light generating SCs with an optimized lipid membrane and internal composition, to maximize luciferase expression levels and enable high-intensity emission. Next, we show these cells' capacity to trigger bioprocesses in natural cells by initiating asexual sporulation of dark-grown mycelial cells of the fungus Trichoderma atroviride. Finally, we demonstrate regulated transcription and membrane recruitment in synthetic cells using bioluminescent intracellular signaling with self-activating fusion proteins. These functionalities pave the way for deploying synthetic cells as embeddable microscale light sources that are capable of controlling engineered processes inside tissues.
Capturing the dynamics of live cell populations with nanoscale resolution poses a significant challenge, primarily owing to the speed-resolution trade-off of existing microscopy techniques. Flow ...cytometry would offer sufficient throughput, but lacks subsample detail. Here we show that imaging flow cytometry, in which the point detectors of flow cytometry are replaced with a camera to record 2D images, is compatible with 3D localization microscopy through point-spread-function engineering, which encodes the depth of the emitter into the emission pattern captured by the camera. The extraction of 3D positions from sub-cellular objects of interest is achieved by calibrating the depth-dependent response of the imaging system using fluorescent beads mixed with the sample buffer. This approach enables 4D imaging of up to tens of thousands of objects per minute and can be applied to characterize chromatin dynamics and the uptake and spatial distribution of nanoparticles in live cancer cells.
Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated ...that brain‐targeted liposomes (BTL) enhance the delivery of mAbs across the blood‐brain‐barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin‐receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha‐synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100‐nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.
The authors highlight a targeted drug delivery system for treating Parkinson's disease. By engineering brain‐targeted liposomes with transferrin on the outer surface of the nanoparticles, and containing therapeutic antibodies, they achieve successful crossing of the blood‐brain‐barrier and effective treatment of brain neurons. This approach reduces alpha‐synuclein aggregation and neuroinflammation, showcasing its potential for delivering biologics in the treatment of neurodegenerative diseases.
Artificial intelligence (AI) and nanotechnology are instrumental in realizing the goal of precision medicine—tailoring the best treatment for each cancer patient. Recent conversion between these ...fields is enabling better patient data acquisition and improved design of nanomaterials. Fundamental concepts in AI and the contributions of nanotechnology and AI to the future of precision cancer medicine are reviewed by Avi Schroeder and co‐workers in article number 1901989. Cover art ‐ Maayan Harel.
Brain‐Targeted Liposomes
In article number 2304654, Avi Schroeder and co‐workers describe a targeted nanotechnology drug delivery system for treating Parkinson's disease. Brain‐targeted ...liposomes—nanoparticles engineered with transferrin on their surface and carry therapeutic antibodies, cross the blood–brain barrier and effectively treat brain neurodegeneration. This approach reduces pathological alpha‐synuclein aggregation and improves motor skills, demonstrating its potential for treating neurodegenerative diseases.
•Polylactic acid (PLA) is a biocompatible polymer that is used widely for biomedical applications.•PLA biodegrades into lactic acid (LA) or to carbon dioxide and water.•PLA degradation products are ...metabolized intracellularly or excreted in the urine and breath.•Adverse reactions or foreign body response to PLA are extremely rare.
Polylactic acid (PLA) is the most commonly used biodegradable polymer in clinical applications today. Examples range from drug delivery systems, tissue engineering, temporary and long-term implantable devices; constantly expanding to new fields. This is owed greatly to the polymer’s favorable biocompatibility and to its safe degradation products. Once coming in contact with biological media, the polymer begins breaking down, usually by hydrolysis, into lactic acid (LA) or to carbon dioxide and water. These products are metabolized intracellularly or excreted in the urine and breath. Bacterial infection and foreign-body inflammation enhance the breakdown of PLA, through the secretion of enzymes that degrade the polymeric matrix.
The biodegradation occurs both on the surface of the polymeric device and inside the polymer body, by diffusion of water between the polymer chains.
The median half-life of the polymer is 30 weeks; however, this can be lengthened or shortened to address the clinical needs. Degradation kinetics can be tuned by determining the molecular composition and the physical architecture of the device. For example, using L- or D-chirality of the LA will greatly lengthen or shorten the degradation rates, respectively.
Despite the fact that this polymer is more than 150 years old, PLA remains a fertile platform for biomedical innovation and fundamental understanding of how artificial polymers can safely coexist with biological systems.
Overexpressed extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) limits drug penetration into the tumor and is associated with poor prognosis. Here, we demonstrate that a ...pretreatment based on a proteolytic-enzyme nanoparticle system disassembles the dense PDAC collagen stroma and increases drug penetration into the pancreatic tumor. More specifically, the collagozome, a 100 nm liposome encapsulating collagenase, was rationally designed to protect the collagenase from premature deactivation and prolonged its release rate at the target site. Collagen is the main component of the PDAC stroma, reaching 12.8 ± 2.3% vol in diseased mice pancreases, compared to 1.4 ± 0.4% in healthy mice. Upon intravenous injection of the collagozome, ∼1% of the injected dose reached the pancreas over 8 h, reducing the level of fibrotic tissue to 5.6 ± 0.8%. The collagozome pretreatment allowed increased drug penetration into the pancreas and improved PDAC treatment. PDAC tumors, pretreated with the collagozome followed by paclitaxel micelles, were 87% smaller than tumors pretreated with empty liposomes followed by paclitaxel micelles. Interestingly, degrading the ECM did not increase the number of circulating tumor cells or metastasis. This strategy holds promise for degrading the extracellular stroma in other diseases as well, such as liver fibrosis, enhancing tissue permeability before drug administration.
Progress in bottom-up synthetic biology has stimulated the development of synthetic cells (SCs), autonomous protein-manufacturing particles, as dynamic biomimetics for replacing diseased natural ...cells and addressing medical needs. Here, we report that SCs genetically encoded to produce proangiogenic factors triggered the physiological process of neovascularization in mice. The SCs were constructed of giant lipid vesicles and were optimized to facilitate enhanced protein production. When introduced with the appropriate genetic code, the SCs synthesized a recombinant human basic fibroblast growth factor (bFGF), reaching expression levels of up to 9⋅10
protein copies per SC. In culture, the SCs induced endothelial cell proliferation, migration, tube formation, and angiogenesis-related intracellular signaling, confirming their proangiogenic activity. Integrating the SCs with bioengineered constructs bearing endothelial cells promoted the remodeling of mature vascular networks, supported by a collagen-IV basement membrane-like matrix. In vivo, prolonged local administration of the SCs in mice triggered the infiltration of blood vessels into implanted Matrigel plugs without recorded systemic immunogenicity. These findings emphasize the potential of SCs as therapeutic platforms for activating physiological processes by autonomously producing biological drugs inside the body.
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