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.
Synthetic cells, artificial cell‐like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for ...revealing the origins‐of‐life. Here, it is shown for the first time that artificial lipid‐based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand‐alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre‐loaded with template DNA, amino acids and energy‐supplying molecules, up to 2 × 107 copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE‐producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on‐demand in diseased tissues.
Synthetic cells contain all the nanoscale molecular machines and building blocks necessary for carrying out transcription and translation, including ribosomes, RNA polymerase, amino acids, and energy. Based on synthetically‐encoded DNA, the particles synthesize diagnostic and therapeutic proteins in tumors.
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.
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.
Personalized medicine promises to revolutionize cancer therapy by matching the most effective treatment to the individual patient. Using a nanoparticle-based system, we predict the therapeutic ...potency of anticancer medicines in a personalized manner. We carry out the diagnostic stage through a multidrug screen performed inside the tumour, extracting drug activity information with single cell sensitivity. By using 100 nm liposomes, loaded with various cancer drugs and corresponding synthetic DNA barcodes, we find a correlation between the cell viability and the drug it was exposed to, according to the matching barcodes. Based on this screen, we devise a treatment protocol for mice bearing triple-negative breast-cancer tumours, and its results confirm the diagnostic prediction. We show that the use of nanotechnology in cancer care is effective for generating personalized treatment protocols.
•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.
Cell-free protein synthesis (CFPS) systems are important laboratory tools that are used for various synthetic biology applications. Here, we present a simple and inexpensive laboratory-scale method ...for preparing a CFPS system from E. coli. The procedure uses basic lab equipment, a minimal set of reagents, and requires less than one hour to process the bacterial cell mass into a functional S30-T7 extract. BL21(DE3) and MRE600 E. coli strains were used to prepare the S30-T7 extract. The CFPS system was used to produce a set of fluorescent and therapeutic proteins of different molecular weights (up to 66 kDa). This system was able to produce 40-150 μg-protein/ml, with variations depending on the plasmid type, expressed protein and E. coli strain. Interestingly, the BL21-based CFPS exhibited stability and increased activity at 40 and 45°C. To the best of our knowledge, this is the most rapid and affordable lab-scale protocol for preparing a cell-free protein synthesis system, with high thermal stability and efficacy in producing therapeutic proteins.
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.
As the world population grows, there is a need for efficient agricultural technologies to provide global food requirements and reduce environmental toll. In medicine, nanoscale drug delivery systems ...grant improved therapeutic precision by overcoming biological barriers and enhancing drug targeting to diseased tissues. Here, we loaded nanoscale drug-delivery systems with agricultural nutrients, and applied them to the leaves of tomato plants. We show that the nanoparticles - liposomes composed of plant-derived lipids, penetrate the leaf and translocate in a bidirectional manner, distributing to other leaves and to the roots. The liposomes were then internalized by the plant cells, where they released their active ingredient. Up to 33% of the applied nanoparticles penetrated the leaf, compared to less than one percent of free-molecules applied in a similar manner. In our study, tomato plants treated with liposomes loaded with Fe and Mg overcame acute nutrient deficiency which was not treatable using ordinary agricultural nutrients. Furthermore, to address regulatory concerns regarding airborne nanoparticles, we rationally designed liposomes that were stable only over short spraying distances (less than 2 meters), while the liposomes disintegrated into safe molecular building blocks (phospholipids) over longer airborne distances. These findings support expanding the implementation of nanotechnology for delivering micronutrients to agricultural crops for increasing yield.
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