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Key Points Nanotechnology concerns the study of devices that are themselves or have essential components in the 1–1,000 nm dimensional range (that is, from a few atoms to subcellular size). Two main subfields of nanotechnology are nanovectors — for the administration of targeted therapeutic and imaging moieties — and the precise patterning of surfaces. Nanotechnology is no stranger to oncology: liposomes are early examples of cancer nanotherapeutics, and nanoscale-targeted magnetic resonance imaging contrast agents illustrate the application of nanotechnology to diagnostics. Photolithography is a light-directed surface-patterning method, which is the technological foundation of microarrays and the surface-enhanced laser desorption/ionization time-of-flight approach to proteomics. Nanoscale resolution is now possible with photolithography, and will give rise to instruments that can pack a much greater density of information than current biochips. The ability of nanotechnology to yield advances in early detection, diagnostics, prognostics and the selection of therapeutic strategies is predicated based on its ability to 'multiplex' — that is, to detect a broad multiplicity of molecular signals and biomarkers in real time. Prime examples of multiplexing detection nanotechnologies are arrays of nanocantilevers, nanowires and nanotubes. Multifunctionality is the fundamental advantage of nanovectors for the cancer-specific delivery of therapeutic and imaging agents. Primary functionalities include the avoidance of biobarriers and biomarker-based targeting, and the reporting of therapeutic efficacy. Thousands of nanovectors are currently under study. By systematically combining them with preferred therapeutic and biological targeting moieties it might be possible to obtain a very large number of novel, personalized therapeutic agents. Novel mathematical models are needed, in order to secure the full import of nanotechnology into oncology. Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

Cancer is a leading cause of morbidity and mortality worldwide, with recent advancements resulting in modest impacts on patient survival. Nanomedicine represents an innovative field with immense potential for improving cancer treatment, having ushered in several established drug delivery platforms. Nanoconstructs such as liposomes are widely used in clinics, while polymer micelles are in advanced phases of clinical trials in several countries. Currently, the field of nanomedicine is generating a new wave of nanoscale drug delivery strategies, embracing trends that involve the functionalization of these constructs with moieties that enhance site‐specific delivery and tailored release. Herein, we discuss several advancements in established nanoparticle technologies such as liposomes, polymer micelles, and dendrimers regarding tumor targeting and controlled release strategies, which are being incorporated into their design with the hope of generating a more robust and efficacious nanotherapeutic modality. We also highlight a novel strategy known as multistage drug delivery; a rationally designed nanocarrier aimed at overcoming numerous biological barriers involved in drug delivery through the decoupling of various tasks that comprise the journey from the moment of systemic administration to arrival at the tumor site. (Cancer Sci 2011; 102: 1247–1252)

Site-specific localization is critical for improving the therapeutic efficacy and safety of drugs. Nanoparticles have emerged as promising tools for localized drug delivery. However, over 90% of systemically injected nanocarriers typically accumulate in the liver and spleen due to resident macrophages that form the mononuclear phagocyte system. In this study, the clinically approved antimalarial agent chloroquine was shown to reduce nanoparticle uptake in macrophages by suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of chloroquine substantially decreased the accumulation of liposomes and silicon particles in the mononuclear phagocyte system and improved tumoritropic and organotropic delivery. The novel use of chloroquine as a macrophage-preconditioning agent presents a straightforward approach for addressing a major barrier in nanomedicine. Moreover, this priming strategy has broad applicability for improving the biodistribution and performance of particulate delivery systems. Ultimately, this study defines a paradigm for the combined use of macrophage-modulating agents with nanotherapeutics for improved site-specific delivery.

•We discuss the frontiers of POC diagnostic technologies using a drop of blood obtained from a finger prick.•A great challenge is still required to develop simple, inexpensive, rapid, and easy-to-use technologies for blood molecular diagnostics.•Proteins, nucleic acids, and other molecules, as well as downstream molecular analyses based on cancer cells isolated from the blood are surveyed for molecular diagnostics in a drop of blood.•Various technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and nonexpensive disease diagnostics. Molecular diagnostics is crucial for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor and time intensive, expensive, and require highly trained operators. This review discusses the frontiers of point-of-care (POC) diagnostic technologies using a drop of blood obtained from a finger prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics.

BackgroundArtificial intelligence (AI) has the potential to enhance patient safety in surgery, and all its aspects, including education and training, will derive considerable benefit from AI. In the present study, deep-learning models were used to predict the rates of proficiency acquisition in robot-assisted surgery (RAS), thereby providing surgical programs directors information on the levels of the innate ability of trainees to facilitate the implementation of flexible personalized training.Methods176 medical students, without prior experience with surgical simulators, were trained to reach proficiency in five tasks on a virtual simulator for RAS. Ensemble deep neural networks (DNN) models were developed and compared with other ensemble AI algorithms, i.e., random forests and gradient boosted regression trees (GBRT).ResultsDNN models achieved a higher accuracy than random forests and GBRT in predicting time to proficiency, 0.84 vs. 0.70 and 0.77, respectively (Peg board 2), 0.83 vs. 0.79 and 0.78 (Ring walk 2), 0.81 vs 0.81 and 0.80 (Match board 1), 0.79 vs. 0.75 and 0.71 (Ring and rail 2), and 0.87 vs. 0.86 and 0.84 (Thread the rings 2). Ensemble DNN models outperformed random forests and GBRT in predicting number of attempts to proficiency, with an accuracy of 0.87 vs. 0.86 and 0.83, respectively (Peg board 2), 0.89 vs. 0.88 and 0.89 (Ring walk 2), 0.91 vs. 0.89 and 0.89 (Match board 1), 0.89 vs. 0.87 and 0.83 (Ring and rail 2), and 0.96 vs. 0.94 and 0.94 (Thread the rings 2).ConclusionsEnsemble DNN models can identify at an early stage the acquisition rates of surgical technical proficiency of trainees and identify those struggling to reach the required expected proficiency level.

BackgroundThere is an increasing interest for a test assessing objectively the innate aptitude for surgery as a craft specialty to complement the current selection process of surgical residents. The aim of this study was to quantify the size of individuals with high, average, and low level of innate psychomotor skills among medical students.MethodsA volunteer sample of 155 medical students, without prior experience with surgical simulator, executed five tasks at a virtual simulator for robot-assisted surgery. They had to reach proficiency twice consecutively in each before moving to the next one. A weighting based on time and number of attempts needed to reach proficiency was assigned to each task.ResultsNine students (5.8%) out of 155 significantly outperformed all the others on median (i.q.r.) weighted time [44.7 (42.2–47.3) min vs. 98.5 (70.8–131.8) min, p < 0.001], and number of attempts to reach proficiency [14 (12–15) vs. 23 (19–32.75), p < 0.001). Seventeen students (11.0%) scored significantly much worse than the rest on median weighted time [202.2 (182.5–221.0) min vs. 84.3 (65.7–114.4) min, p < 0.001], and number of attempts [42 (40–48) vs. 22 (17.25–28), p < 0.001]. Low correlation between simulator scores and extracurricular activities, like videogames and musical instruments, was found.ConclusionsThe test successfully identified two groups straddling the large cohort with average innate aptitude for psychomotor skills: (i) innately gifted and (ii) with scarce level. Hence, exercises on a virtual simulator are a valid test of innate manual dexterity and can be considered to complement the selection process for a surgical training program, primarily to identify individuals with low innate aptitude for surgery and advise them to consider specialization in other (non-craft) medical specialties.

Ionic transport through nanofluidic systems is a problem of fundamental interest in transport physics and has broad relevance in desalination, fuel cells, batteries, filtration, and drug delivery. When the dimension of the fluidic system approaches the size of molecules in solution, fluid properties are not homogeneous and a departure in behavior is observed with respect to continuum-based theories. Here we present a systematic study of the transport of charged and neutral small molecules in an ideal nanofluidic platform with precise channels from the sub-microscale to the ultra-nanoscale (<5 nm). Surprisingly, we find that diffusive transport of nano-confined neutral molecules matches that of charged molecules, as though the former carry an effective charge. Further, approaching the ultra-nanoscale molecular diffusivities suddenly drop by up to an order of magnitude for all molecules, irrespective of their electric charge. New theoretical investigations will be required to shed light onto these intriguing results. Transport through nanochannels is usually dominated by electrostatic interactions and depends on the charge of diffusing molecules. Here the authors show that for channel heights between 2 and 4 nanometers, transport is insensitive to molecule charge.

The physics of mass transport within body compartments and across biological barriers differentiates cancers from healthy tissues. Variants of nanoparticles can be manufactured in combinatorially large sets, varying by only one transport-affecting design parameter at a time. Nanoparticles can also be used as building blocks for systems that perform sequences of coordinated actions, in accordance with a prescribed logic. We refer to these as Logic-Embedded Vectors (LEVs). Nanoparticles and LEVs are ideal probes for the determination of mass transport laws in tumors, acting as imaging contrast enhancers, and can be employed for lesion-selective delivery of therapy. Their size, shape, density and surface chemistry dominate convective transport in the bloodstream, margination, cell adhesion, selective cellular uptake, as well as sub-cellular trafficking and localization. As argued here, the understanding of transport differentials in cancer, termed ‘transport oncophysics’, reveals a promising new frontier in oncology: the development of lesion-specific delivery particulates that exploit mass transport differentials to deploy treatment of greater efficacy and reduced side effects.

Magnetic resonance imaging contrast agents are currently designed by modifying their structural and physiochemical properties to improve relaxivity and to enhance image contrast. Here, we show a general method for increasing relaxivity by confining contrast agents inside the nanoporous structure of silicon particles. Magnevist, gadofullerenes and gadonanotubes were loaded inside the pores of quasi-hemispherical and discoidal particles. For all combinations of nanoconstructs, a boost in longitudinal proton relaxivity r 1 was observed: Magnevist, r 1  ≈ 14 mM −1  s −1 /Gd 3+ ion (∼8.15 × 10 +7  mM −1  s −1 /construct); gadofullerenes, r 1  ≈ 200 mM −1  s −1 /Gd 3+ ion (∼7 × 10 +9  mM −1  s −1 /construct); gadonanotubes, r 1  ≈ 150 mM −1  s −1 /Gd 3+ ion (∼2 × 10 +9  mM −1  s −1 /construct). These relaxivity values are about 4 to 50 times larger than those of clinically available gadolinium-based agents (∼4 mM −1  s −1 /Gd 3+ ion). The enhancement in contrast is attributed to the geometrical confinement of the agents, which influences the paramagnetic behaviour of the Gd 3+ ions. Thus, nanoscale confinement offers a new and general strategy for enhancing the contrast of gadolinium-based contrast agents. Confining gadolinium-based contrast agents inside the porous structure of silicon microparticles can improve their T 1 contrast, offering a general approach for developing highly efficient MRI contrast agents.

Augmented Reality (AR) headsets have become the most ergonomic and efficient visualization devices to support complex manual tasks performed under direct vision. Their ability to provide hands-free interaction with the augmented scene makes them perfect for manual procedures such as surgery. This study demonstrates the reliability of an AR head-mounted display (HMD), conceived for surgical guidance, in navigating in-depth high-precision manual tasks guided by a 3D ultrasound imaging system. The integration between the AR visualization system and the ultrasound imaging system provides the surgeon with real-time intra-operative information on unexposed soft tissues that are spatially registered with the surrounding anatomic structures. The efficacy of the AR guiding system was quantitatively assessed with an in vitro study simulating a biopsy intervention aimed at determining the level of accuracy achievable. In the experiments, 10 subjects were asked to perform the biopsy on four spherical lesions of decreasing sizes (10, 7, 5, and 3 mm). The experimental results showed that 80% of the subjects were able to successfully perform the biopsy on the 5 mm lesion, with a 2.5 mm system accuracy. The results confirmed that the proposed integrated system can be used for navigation during in-depth high-precision manual tasks.