Preventing Metastasis Using Gold Nanorod-Assisted Plasmonic Photothermal Therapy in Xenograft Mice.

Despite significant research regarding metastasis, there has been limited success in preventing it. However, gold nanoparticle (AuNP) technology has shown the potential to inhibit metastasis. Our earlier studies of gold nanorod-assisted plasmonic photothermal therapy (AuNRs-PPTT), where gold nanorods (AuNRs) were irradiated with near-infrared (NIR) light to induce heat, were utilized in slowing cancer cell migration in vitro. Herein, we have expanded the in vitro studies of the AuNRs-PPTT to xenograft mice to inhibit metastasis of mammary gland tumors. The study duration was 32 days from 4T1 cancer cell injections in four treatment groups: control (PBS), NIR Only, AuNRs, and AuNRs + NIR. Multiple AuNRs-PPTT treatment sessions with intratumoral AuNRs injections were conducted every 7 days on average on the mice. Photoacoustic spectroscopy has been utilized to study the distribution and aggregation of AuNRs within the tumors and the drainage of particles to the sentinel right subiliac lymph node. The photoacoustic results revealed that the AuNRs' shapes are still stable regardless of their heterogeneous distributions inside the mammalian tumor and lymph nodes. Bioluminescence imaging was used to monitor metastasis using luciferin labeling techniques and has shown that AuNRs-PPTT inhibited metastasis completely within the first 21 days. Moreover, proteomics was run to determine the most pivotal inhibitory pathways: NETosis, cell growth, cell proliferation, inflammation, and extracellular matrix (ECM) degradation. These five mechanisms are interdependent within related networks, which synergistically explains the molecular mechanism of metastasis inhibition by AuNRs-PPTT. The current in vivo data ensures the viability of PPTT applications in inhibiting metastasis in humans.

Impact of Intermolecular Non-Covalent Interactions in a CuI 8 PdII 1 Discrete Assembly: Conformers' Geometries and Stimuli-Sensitive Luminescence Properties.

A new highly solid-state luminescent phase of a previously reported weakly luminescent CuI 8 PdII 1 dicationic assembly is reported revealing the high geometrical versatility of this moiety that importantly alters its luminescent properties. This very minor new species Bc is based on a different conformer scaffold than the one encountered in the previously reported Bo form and, essentially differs from Bo by displaying shorter CuI -CuI intermetallic distances. DFT calculations allow concluding that the predominance in the solid-state of the weakly luminescent and less stable Bo phase is due to the extra stability induced by a larger number of intermolecular non-covalent π-CH interactions in its crystalline packing and not by the intrinsic stability of the CuI 8 PdII 1 dicationic moiety. Calculations also revealed that a more stable conformation Bcalc is expected in vacuum, which bears a different distribution of CuI -CuI intermetallic distances than the dications in Bo and Bc phases. Taking into account that the geometrical alterations are associated to drastic changes of luminescence properties, this confer to the CuI 8 PdII 1 assembly high potentiality as stimuli-sensitive luminescent materials. Indeed, by applying mechanical or thermal stress to samples of Bo phase, new phases Bg and Bm , respectively, were obtained. Alterations of the solid-state photophysical properties of these new species compared to those recorded for Bo are reported together with a combined experimental and computed study of the structures/properties relationships observed in these phases.

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins.

Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.

Efficacy, long-term toxicity, and mechanistic studies of gold nanorods photothermal therapy of cancer in xenograft mice.

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm2) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome c and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.

Improving the Flow Cytometry-based Detection of the Cellular Uptake of Gold Nanoparticles.

Due to the considerable amount of applications of gold nanoparticles (AuNPs) in biological systems, there is a great need for an improved methodology to quantitatively measure the uptake of AuNPs in cells. Flow cytometry has the ability to measure intracellular AuNPs by collecting the light scattering from a large population of live cells through efficient single cell analysis. Traditionally, the side scattering setting of the flow cytometer, which is associated with a 488 nm excitation laser (SSC channel), is used to detect nanoparticle uptake. This method is limited as AuNPs do not have the optimized response when excited with this laser. Here, we reported that the use of more red-shifted excitation lasers will greatly enhance the optical signal needed for the flow cytometry-based detection of AuNSs (26 nm in diameter) and AuNRs (67 nm × 33 nm, length × width) uptake in triple negative breast cancer cells (MDA-MB-231).

Adaptive Coordination-Driven Supramolecular Syntheses toward New Polymetallic Cu(I) Luminescent Assemblies.

A thermally activated delayed fluorescence (TADF) tetrametallic Cu(I) metallacycle A behaves as a conformationally adaptive preorganized precursor to afford, through straightforward and rational coordination-driven supramolecular processes, a variety of room-temperature solid-state luminescent polymetallic assemblies. Reacting various cyano-based building blocks with A, a homometallic Cu(I) 1D-helical coordination polymer C and Cu8M discrete circular heterobimetallic assemblies DM (M = Ni, Pd, Pt) are obtained. Their luminescence behaviors are studied, revealing notably the crucial impact of the spin-orbit coupling offered by the central M metal center on the photophysical properties of the heterobimetallic DM derivatives.

Simultaneous Time-Dependent Surface-Enhanced Raman Spectroscopy, Metabolomics, and Proteomics Reveal Cancer Cell Death Mechanisms Associated with Gold Nanorod Photothermal Therapy.

In cancer plasmonic photothermal therapy (PPTT), plasmonic nanoparticles are used to convert light into localized heat, leading to cancer cell death. Among plasmonic nanoparticles, gold nanorods (AuNRs) with specific dimensions enabling them to absorb near-infrared laser light have been widely used. The detailed mechanism of PPTT therapy, however, still remains poorly understood. Typically, surface-enhanced Raman spectroscopy (SERS) has been used to detect time-dependent changes in the intensity of the vibration frequencies of molecules that appear or disappear during different cellular processes. A complete proven assignment of the molecular identity of these vibrations and their biological importance has not yet been accomplished. Mass spectrometry (MS) is a powerful technique that is able to accurately identify molecules in chemical mixtures by observing their m/z values and fragmentation patterns. Here, we complemented the study of changes in SERS spectra with MS-based metabolomics and proteomics to identify the chemical species responsible for the observed changes in SERS band intensities during PPTT. We observed an increase in intensity of the bands at around 1000, 1207, and 1580 cm-1, which were assigned in the literature to phenylalanine, albeit with dispute. Our metabolomics results showed increased levels of phenylalanine, its derivatives, and phenylalanine-containing peptides, providing evidence for more confidence in the SERS peak assignments. To better understand the mechanism of phenylalanine increase upon PPTT, we combined metabolomics and proteomics results through network analysis, which proved that phenylalanine metabolism was perturbed. Furthermore, several apoptosis pathways were activated via key proteins (e.g., HADHA and ACAT1), consistent with the proposed role of altered phenylalanine metabolism in inducing apoptosis. Our study shows that the integration of the SERS with MS-based metabolomics and proteomics can assist the assignment of signals in SERS spectra and further characterize the related molecular mechanisms of the cellular processes involved in PPTT.

Gold Nanorods as Drug Delivery Vehicles for Rifampicin Greatly Improve the Efficacy of Combating Mycobacterium tuberculosis with Good Biocompatibility with the Host Cells.

TB remains a challenging disease to control worldwide. Nanoparticles have been used as drug carriers to deliver high concentrations of antibiotics directly to the site of infection, reducing the duration of treatment along with any side effects of off-target toxicities after systemic exposure to the antibiotics. Herein we have developed a drug delivery platform where gold nanorods (AuNRs) are conjugated to rifampicin (RF), which is released after uptake into macrophage cells (RAW264.7). Due to the nature of the macrophage cells, the nanoparticles are actively internalized into macrophages and release RF after uptake, under the safety frame of the host cells (macrophage). AuNRs without RF conjugation exhibit obvious antimicrobial activity. Therefore, AuNRs could be a promising antimycobacterial agent and an effective delivery vehicle for the antituberculosis drug Rifampicin for use in tuberculosis therapy.

Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats.

Plasmonic photothermal therapy (PPTT) was introduced as a promising treatment of cancer. This work was conducted to evaluate the cytotoxic effect of intratumoral (IT) injection of 75µg gold nanorods (GNRs)/kg of body weight followed by direct exposure to 2 w/cm2 near infra-red laser light for 10min on ablation of mammary tumor in 10 dogs and 6 cats. Complete blood count (CBC), liver and kidney function were checked before the start of treatment and one month after injection of GNRs. Results showed that 62.5% (10/16), 25% (4/16) and 12.5% (2/16) of treated animals showed complete remission, partial remission and no response, respectively. Tumor was relapsed in 4 cases of initially responding animals (25%). Overall survival rate was extended to 315.5±20.5days. GNRs have no toxic effect on blood profile, liver or kidney functions. In conclusion, GNRs can be safely used for treatment of mammary tumors in dogs and cats.

Enhancing the efficiency of gold nanoparticles treatment of cancer by increasing their rate of endocytosis and cell accumulation using rifampicin.

To minimize the toxicity of gold nanoparticles (AuNPs) in cancer treatment, we have developed a technique, which utilizes lesser amount of AuNPs while exhibiting increased treatment efficiency. Rifampicin (RF) is known for its ability to enhance the accumulation of anticancer drugs in multidrug resistant (MDR) cancer cells. In this work we have shown that RF-conjugated AuNPs can greatly enhance the rate as well as efficiency of endocytosis of NPs and hence their concentration inside the cancer cell. Cell viability results showed a remarkable enhancement in the photothermal therapeutic effect of Au nanorods in presence of RF. This is expected to decrease the demand on the overall amount of AuNPs needed for treating cancer and thus decreasing its toxicity.

Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?

PURPOSE: The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response. PATIENTS AND METHODS: A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled. RESULTS: One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set. CONCLUSION: Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.

Diagnostic value of repeated comprehensive investigation with CT urography and cystoscopy for recurrent macroscopic haematuria.

Objectives: To perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria. Methods: All patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015-2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed. Results: A total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow-up of 6.2 (IQR 5.3-7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low-grade UBC (TaG1-2), one with T2G3 UBC and one with low-risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria. Conclusion: In the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.

Optimal Operation of an Industrial Dividing Wall Column through Multiparametric Programming.

In this contribution, we present a high-fidelity dynamic model of an industrial dividing wall column and the application of explicit model predictive control for its regulation. Our study involves the separation of methyl methacrylate from a quaternary mixture. The process includes a dividing wall column coupled with a decanter, which results in highly concentrated methyl methacrylate and water streams from the middle side draw of the column and the decanter, respectively. An equation-oriented mathematical model of the process is developed and presented in detail, where non-ideal thermodynamic calculations are adopted to describe the complex nature of the component interactions. The operability of the process is enhanced by the synthesis and application of an explicit model predictive controller, which is used to track the purity specifications of the product. Our results demonstrate that the proposed modeling and control approach can be utilized for the optimal online operation of the studied system.

Microfluidics for Development of Lipid Nanoparticles: Paving the Way for Nucleic Acids to the Clinic.

Nucleic acid therapeutics hold an unprecedented promise toward treating many challenging diseases; however, their use is hampered by delivery issues. Microfluidics, dealing with fluids in the microscale dimensions, have provided a robust means to screening raw materials for development of nano delivery vectors, in addition to controlling their size and minimizing their polydispersity. In this mini-review, we are briefly highlighting the different types of nucleic acid therapies with emphasis on the delivery requirement for each type. We provide a thorough review of available methods for the development of nanoparticles, especially lipid nanoparticles (LNPs) that resulted in FDA approval of the first ever nucleic acid nanomedicine. We then focus on recent research attempts for how microfluidic synthesis of lipid nanoparticles and discuss the various parameters required for successful formulation of LPNs including chip design, flow regimes, and lipid composition. We then identify key areas of research in microfluidics and related fields that require attention for future success in clinical translation of nucleic acid nanomedicines.

Binary Classification of the Endocrine Disrupting Chemicals by Artificial Neural Networks.

We develop a machine learning framework that integrates high content/high throughput image analysis and artificial neural networks (ANNs) to model the separation between chemical compounds based on their estrogenic receptor activity. Natural and man-made chemicals have the potential to disrupt the endocrine system by interfering with hormone actions in people and wildlife. Although numerous studies have revealed new knowledge on the mechanism through which these compounds interfere with various hormone receptors, it is still a very challenging task to comprehensively evaluate the endocrine disrupting potential of all existing chemicals and their mixtures by pure in vitro or in vivo approaches. Machine learning offers a unique advantage in the rapid evaluation of chemical toxicity through learning the underlying patterns in the experimental biological activity data. Motivated by this, we train and test ANN classifiers for modeling the activity of estrogen receptor-α agonists and antagonists at the single-cell level by using high throughput/high content microscopy descriptors. Our framework preprocesses the experimental data by cleaning, scaling, and feature engineering where only the middle 50% of the values from each sample with detectable receptor-DNA binding is considered in the dataset. Principal component analysis is also used to minimize the effects of experimental noise in modeling where these projected features are used in classification model building. The results show that our ANN-based nonlinear data-driven framework classifies the benchmark agonist and antagonist chemicals with 98.41% accuracy.

Synthesis and optical properties of small Au nanorods using a seedless growth technique.

Gold nanoparticles have shown potential in photothermal cancer therapy and optoelectronic technology. In both applications, a call for small size nanorods is warranted. In the present work, a one-pot seedless synthetic technique has been developed to prepare relatively small monodisperse gold nanorods with average dimensions (length × width) of 18 × 4.5 nm, 25 × 5 nm, 15 × 4.5 nm, and 10 × 2.5 nm. In this method, the pH was found to play a crucial role in the monodispersity of the nanorods when the NaBH(4) concentration of the growth solution was adjusted to control the reduction rate of the gold ions. At the optimized pH and NaBH(4) concentrations, smaller gold nanorods were produced by adjusting the CTAB concentration in the growth solution. In addition, the concentration of silver ions in the growth solution was found to be pivotal in controlling the aspect ratio of the nanorods. The extinction coefficient values for the small gold nanorods synthesized with three different aspect ratios were estimated using the absorption spectra, size distributions, and the atomic spectroscopic analysis data. The previously accepted relationships between the extinction coefficient or the longitudinal band wavelength values and the nanorods' aspect ratios found for the large nanorods do not extend to the small size domain reported in the present work. The failure of extending these relationships over larger sizes is a result of the interaction of light with the large rods giving an extinction band which results mostly from scattering processes while the extinction of the small nanorods results from absorption processes.

Towards more efficient inhalable chemotherapy: Fabrication of nanodiamonds-releasing microspheres.

Nanodiamonds (NDs) are among the most promising chemotherapy vectors, however, they tend to aggregate upon storage, or when exposed to mild changes in pH or ionic strength. Therefore, fabrication of dried NDs with minimal change in particle size is highly desirable. In this study, we have developed a dried powder form of NDs with controlled particle size to be eligible for pulmonary delivery, after screening different drying protectants for their effect on NDs particle size and surface charge. Results showed that the nanospray-drying process in the presence of mannitol prevented the aggregation of NDs. Nanospray-dried NDs microparticles exhibited an optimal aerodynamic size for pulmonary delivery, and the in vitro aerosol deposition testing showed that NDs-embedded mannitol microspheres could deliver more than half of the emitted fraction to the lower stage of the Twin impinger device; indicating high pulmonary delivery potential. Upon loading NDs with doxorubicin (NDX) prior to spray dryng, they were able to deliver 2.6 times more drug to A549 lung cancer cell line compared to the free drug. Pharmacokinetics study in rats showed that inhaled NDX microparticles could efficiently limit the biodistribution of the drug to the lungs, and minimize the drug fraction reaching the systemic circulation. To conclude, nanospray-dried NDs microparticles present a promising vehicle for the pulmonary delivery of chemotherapeutic agents for treatment of lung cancer.

Effect of titanium dioxide nanoparticles and ß-cyclodextrin polymer on physicochemical, antimicrobial, and antibiofilm properties of a novel chitosan-camphor polymer.

In this paper, chitosan (Chi) was successfully reacted with natural mono ketone namely, camphor (Cam), through a condensation reaction to obtain a novel Chi-Cam polymer. The encapsulation of Chi-Cam polymer into the cavity of ß-cyclodextrin biopolymer by inclusion complex method, and the immobilization of TiO2 NPs into Chi-Cam matrix by metal complex method were performed. A set of characterizations (XRD, FTIR, SEM, UV-Vis., optical band gap, Urbach energy, refractive index, and thermogravimetric analysis) were implemented to incorporate their properties with applications. It was not observed the existence of any strange peaks in diffractogram patterns of all prepared samples, confirming the proper preparation and high purity polymers. The crystalline index was found to be 69.41, 41.58, 58.25 and 44.2 % for Chi, Chi-Cam, polyrotaxane, and nanocomposite, respectively. High surface area, lowest pores size, and lowest pores volume were confirmed the micropores of composite, which also could provide more reactive sites, and enhancing the bioactivity. The tested Chi-Cam/TiO2 NPs possessed the highest antimicrobial impact, followed by the Chi-Cam/ß-CD towards pathogenic microbes. The highest % inhibition of biofilm formation by Chi-Cam, Chi-Cam/ß-CD, and Chi-Cam/TiO2 NPs was noted for S. aureus (40.05 %, 80.21 %, and 87.49 %), E. coli (38.56 %, 74.32 % and 83.32 %), P. aureginosa (32.12 %, 58.80 %, and 74.53 %), and C. albicans (13.69 %, 27.89 % and 70.89 %), respectively. The obtaining findings pave the route towards useful utilization of potential materials for biomedical applications.

Dynamic placenta-on-a-chip model for fetal risk assessment of nanoparticles intended to treat pregnancy-associated diseases.

Pregnant women often have to take medication either for pregnancy-related diseases or for previously existing medical conditions. Current maternal medications pose fetal risks due to off target accumulation in the fetus. Nanoparticles, engineered particles in the nanometer scale, have been used for targeted drug delivery to the site of action without off-target effects. This has opened new avenues for treatment of pregnancy-associated diseases while minimizing risks on the fetus. It is therefore instrumental to study the potential transfer of nanoparticles from the mother to the fetus. Due to limitations of in vivo and ex vivo models, an in vitro model mimicking the in vivo situation is essential. Placenta-on-a-chip provides a microphysiological recapitulation of the human placenta. Here, we reviewed the fetal risks associated with current therapeutic approaches during pregnancy, analyzed the advantages and limitations of current models used for nanoparticle assessment, and highlighted the current need for using dynamic placenta-on-a-chip models for assessing the safety of novel nanoparticle-based therapies during pregnancy.