Are quantum dots ready for in vivo imaging in human subjects?

Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.     

Gold-Nanoparticle-Decorated Metal-Organic Frameworks for Anticancer Therapy

Confinement of Au nanoparticles (NPs) within the porous materials with few nanometers (2-3 nm) has been a well established research area in the past decades in heterogeneous catalysis mainly due to the unique behaviour of Au NPs than its bulk counterpart. In this aspect, Au NPs encapsulated within the pore volumes of metal−organic frameworks (MOFs) have been intensively explored as heterogeneous solid catalysts for wide range of reactions. In recent years, Au NPs confined within the porous MOFs along with the photosensitizer or drug have been effectively used for the treatment of tumor cells through the generation of reactive oxygen species via cascade reactions. This work highlights the benefits of MOFs pores in the preparation of nanomedicine with high efficiency by assembling Au NPs, photosensitizer/drug with the combination of laser either for imaging or treatment of tumor cells. Further, the existing literature is grouped based on the nature of porous materials employed in the preparation of nanomedicine. The final section comments on our view on future developments in the field.     

Quantifying spectral changes experienced by plasmonic nanoparticles in a cellular environment to inform biomedical nanoparticle design

Metal nanoparticles (NPs) scatter and absorb light in precise, designable ways, making them agile candidates for a variety of biomedical applications. When NPs are introduced to a physiological environment and interact with cells, their physicochemical properties can change as proteins adsorb on their surface and they agglomerate within intracellular endosomal vesicles. Since the plasmonic properties of metal NPs are dependent on their geometry and local environment, these physicochemical changes may alter the NPs'' plasmonic properties, on which applications such as plasmonic photothermal therapy and photonic gene circuits are based. Here we systematically study and quantify how metal NPs'' optical spectra change upon introduction to a cellular environment in which NPs agglomerate within endosomal vesicles. Using darkfield hyperspectral imaging, we measure changes in the peak wavelength, broadening, and distribution of 100-nm spherical gold NPs'' optical spectra following introduction to human breast adenocarcinoma Sk-Br-3 cells as a function of NP exposure dose and time. On a cellular level, spectra shift up to 78.6 ± 23.5 nm after 24 h of NP exposure. Importantly, spectra broaden with time, achieving a spectral width of 105.9 ± 11.7 nm at 95% of the spectrum''s maximum intensity after 24 h. On an individual intracellular NP cluster (NPC) level, spectra also show significant shifting, broadening, and heterogeneity after 24 h. Cellular transmission electron microscopy (TEM) and electromagnetic simulations of NPCs support the trends in spectral changes we measured. These quantitative data can help guide the design of metal NPs introduced to cellular environments in plasmonic NP-mediated biomedical technologies.     

Stigmergic cooperation of nanoparticles for swarm fuzzy control of low-density lipoprotein concentration in the arterial wall

This paper proposes the use of stigmergic cooperation between two swarms of Fuzzy Nanoparticles (FNPs) and Auxiliary Nanoparticles (ANPs) for intelligent control of Low-Density Lipoprotein (LDL) concentration in the arterial wall, as a novel non-invasive method for prevention of atherosclerosis. Given any desired fuzzy controller, a swarm of FNPs in the aqueous environment of a living tissue can collectively realize an accurate approximation of this controller, which is called swarm fuzzy controller. In this study, the task of the swarm fuzzy controller is to manipulate the pheromone level of the environment as output according to the sensed value of LDL concentration as input. Pheromone is a chemical substance that is used for stigmergic communication between two swarms of FNPs and ANPs. An ANP consists of a drug reservoir connected to a nanoscale valve which is controllable by pheromone concentration. The level of pheromone in the local environment of an ANP determines how much drug should be released by it. The hardware complexity of the proposed approach is lower than nanorobotics to facilitate its manufacturing. Simulation results on a well-known mathematical model demonstrate that this method can successfully reduce the LDL level to a desired value in the arterial wall of a patient with very high LDL level, while its performance is much better in contrast to the previous work of authors. Also, the mass of the released drug in a healthy wall is 16 times lesser than its corresponding value in an unhealthy wall.     

Nanoinformatics in Drug Delivery

The use of nanomedicine for targeted drug delivery, though well established, is still a growing and developing field of research with potential benefits to many biomedical problems. There is a plethora of nano-carriers with myriads of designs of shapes, sizes and composition that involves complex, trial and error based preparation protocols. The digital age brought an information revolution with automated data analysis, machine learning and data mining applied to almost every field of research including drug delivery. Indeed, nanomedicine has benefitted from the use of data science and information science to optimize, standardize, and understand the synthesis, characterization, and biological effects of nanomaterials. This short review will describe several concepts and a few examples of nanoinformatics, including Nano-Quantitative Structure-Activity Relationship (Nano-QSAR), the use of computational methods for predicting different properties of nanomedicine in drug delivery and propose an outlook for the future.     

Nanoparticles for improving cancer diagnosis

Despite the progress in developing new therapeutic modalities, cancer remains one of the leading diseases causing human mortality. This is mainly attributed to the inability to diagnose tumors in their early stage. By the time the tumor is confirmed, the cancer may have already metastasized, thereby making therapies challenging or even impossible. It is therefore crucial to develop new or to improve existing diagnostic tools to enable diagnosis of cancer in its early or even pre-syndrome stage. The emergence of nanotechnology has provided such a possibility. Unique physical and physiochemical properties allow nanoparticles to be utilized as tags with excellent sensitivity. When coupled with the appropriate targeting molecules, nanoparticle-based probes can interact with a biological system and sense biological changes on the molecular level with unprecedented accuracy. In the past several years, much progress has been made in applying nanotechnology to clinical imaging and diagnostics, and interdisciplinary efforts have made an impact on clinical cancer management. This article aims to review the progress in this exciting area with emphases on the preparation and engineering techniques that have been developed to assemble “smart” nanoprobes.     

Coordinating microscopic robots in viscous fluids

Multiagent control provides strategies for aggregating microscopic robots (“nanorobots”) in fluid environments relevant for medical applications. Unlike larger robots, viscous forces and Brownian motion dominate the behavior. Examples range from modified microorganisms (programmable bacteria) to future robots using ongoing developments in molecular computation, sensors and motors. We evaluate controls for locating a cell-sized area emitting a chemical into a moving fluid with parameters corresponding to chemicals released in response to injury or infection in small blood vessels. These control methods are passive Brownian motion, following the chemical concentration gradient, and cooperative behaviors in which some robots use acoustic signals to guide others to the chemical source. Control performance is evaluated using diffusion equations to describe the robot motions and control state transitions. The quantitative results show these control techniques are feasible approaches to the task with trade-offs among fabrication difficulty, response speed, false positive detection rate and energy use. Controlled aggregation at chemically distinctive locations could be useful for sensitive diagnosis, selective changes to biological tissues and forming structures using previous proposals for multiagent control of modular robots.     

Cs corrected STEM EELS: Analysing beam sensitive carbon nanomaterials in cellular structures

Identification of individual single wall nanotubes (SWNTs) within a cellular structure can provide vital information towards understanding the potential mechanisms of uptake, their localisation and whether their structure is transformed within a cell. To be able to image an individual SWNT in such an environment a resolution is required that is not usually appropriate for biological sections. Standard transmission electron microscopy (TEM) techniques such as bright field imaging of these cellular structures result in very weak contrast. Traditionally, researchers have stained the cells with heavy metal stains to enhance the cellular structure, however this can lead to confusion when analysing the samples at high resolution. Subsequently, alternative methods have been investigated to allow high resolution imaging and spectroscopy to identify SWNTs within the cell; here we will concentrate on the sample preparation and experimental methods used to achieve such resolution.     

Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy

Extracellular matrix (ECM) is not only a natural bulwark to shield solid tumor cells from therapeutic agents and cytotoxic T lymphocytes (CTLs), but also one of the key factors that cause tumor hypoxic environment, severely hindering photodynamic reactions and immune responses. In this work, multifunctional nanoscavengers (ECMT NS) consisting of digestive enzyme chymotrypsin, catalase, calcium peroxide nanoparticles, photosensitizer chlorin e6, and tumor ECM-targeting CLT1 peptide are rationally designed with several benefits for enhanced cocktail calcium ion/photodynamic/immune therapy. The scavengers can effectively “clear” tumor ECM via digestive proteolytic enzyme- and reactive oxygen species-mediated pathways, deepening tumor penetration of the scavengers and CTLs. Thanks to the ECM destruction and oxygen self-supply capability of ECMT NS, the hypoxia in tumors is attenuated, thus improving photodynamic therapeutic efficiency and downregulating immunosuppressive factors. Moreover, the combination of calcium ion overload and photodynamic therapy enriches damage-associated molecular patterns, which promotes CTL activation to inhibit abscopal tumor growth and lung metastasis. The presented ECM destruction strategy provides a solution to overcome the tumor suppressive microenvironment.