Phage Display Technology in Biomarker Identification with Emphasis on Non-Cancerous Diseases.

In recent years, phage display technology has become vital in clinical research. It helps create antibodies that can specifically bind to complex antigens, which is crucial for identifying biomarkers and improving diagnostics and treatments. However, existing reviews often overlook its importance in areas outside cancer research. This review aims to fill that gap by explaining the basics of phage display and its applications in detecting and treating various non-cancerous diseases. We focus especially on its role in degenerative diseases, inflammatory and autoimmune diseases, and chronic non-communicable diseases, showing how it is changing the way we diagnose and treat illnesses. By highlighting important discoveries and future possibilities, we hope to emphasize the significance of phage display in modern healthcare.

Construction and evaluation of wild and mutant ofatumumab scFvs against the human CD20 antigen.

Several monoclonal antibodies targeting the CD20 have been produced and Ofatumumab is a case in point. Although whole antibodies target cancer cells effectively, their applications are restricted in some ways. Single-chain fragment variable antibodies, rather than employing the entire structure of antibodies, have proven a practical approach for creating completely functional antigen-binding fragments. In current research, the DNA coding sequence of VL and VH of the wild and mutant forms of ofatumumab were joined with a flexible linker (GGGGS)3 separately. Using the E. coli BL21 (DE3) expression system, the VL-linker-VH genes were cloned into the pET-28 a (+), and the associated recombinant proteins were produced. Purified and refolded scFvs (scFv-C and scFv-V3) represented a concentration of around 0.7 mg/ml from 1 L of initial E. coli culture with a molecular weight of about 27 kDa. Affinity measurement disclosed anti-CD20 scFv-V3 possesses a higher affinity constant compared to anti-CD20 scFv-C. The recombinant scFvs exclusively attach to Raji cells but not to Jurkat cells, according to a cell-ELISA analysis. The MTT test signified anti-CD20 scFvs could affect cell viability in Raji cells but had no impact on Jurkat cells and also, Raji cells viability was affected more significantly by anti-CD20 scFv-V3.

Long non-coding RNA MIR4435-2HG: a key molecule in progression of cancer and non-cancerous disorders.

MIR4435-2HG (LINC00978) is a long non-coding RNA (lncRNA) that acts as an oncogene in almost all cancers. This lncRNA participates in the molecular cascades involved in other disorders such as coronary artery diseases, osteonecrosis, osteoarthritis, osteoporosis, and periodontitis. MIR4435-2HG exerts its functions via the spectrum of different mechanisms, including inhibition of apoptosis, sponging microRNAs (miRNAs), promoting cell proliferation, increasing cell invasion and migration, and enhancing epithelial to mesenchymal transition (EMT). MIR4435-2HG can regulate several signaling pathways, including Wnt, TGF-ß/SMAD, Nrf2/HO-1, PI3K/AKT, MAPK/ERK, and FAK/AKT/ß­catenin signaling pathways; therefore, it can lead to tumor progression. In the present review, we aimed to discuss the potential roles of lncRNA MIR4435-2HG in developing cancerous and non-cancerous conditions. Due to its pivotal role in different disorders, this lncRNA can serve as a potential biomarker in future investigations. Moreover, it may serve as a potential therapeutic target for the treatment of various diseases.

Atomistic insight into 2D COFs as antiviral agents against SARS-CoV-2.

The recent pandemic of COVID-19 has raised global health concerns. Preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) activity in the body is a very promising method to overcome the COVID-19 pandemic. One of the prevention methods is constraining the binding process among the human cell receptor-ACE2 and coronavirus spike protein. In the research done, the effect of deformation of the spike protein structure, due to the covalent organic frameworks (COFs), in reducing the interactions of ACE2 and the spike protein by the computational method was investigated. In this regard, atomic analysis of the interactions of ACE2 and the spike protein is provided using a molecular dynamics simulation. First, we investigated the interactions of the three different COFs, including COF-78, DAAQ-TFP, and COF-OEt, with the spike protein by analyzing the bond energies, as well as structural changes of the spike protein. Then, intermolecular interactions of the deformed spike protein along with ACE2 were assessed to clarify the protein's fusion after the deformation. As indicated by the results, although all introduced COFs deformed the spike protein in an effective way, COF-78 showed the best performance in the prevention of spike protein-ACE2 interactions by changing the molecular structure of the protein. Indeed, the interaction analysis of the deformed spike protein by COF-78 with the ACE2 showed that their interactions had the lowest absolute value of energy, along with the least amount of hydrogen bonds, in which the compaction of the protein was lower compared to the other deformed proteins. Moreover, having a high contact area with an aqueous media as well as severe fluctuations during the simulation time confirmed the positive performance of COF-78. In the current study, we aimed to introduce novel materials and COVID-19 prevention methodology that can be used in face masks and for surface disinfection.

ß-Amyloid Targeting with Two-Dimensional Covalent Organic Frameworks: Multi-Scale In-Silico Dissection of Nano-Biointerface.

Cytotoxic aggregation of misfolded ß-amyloid (Aß) proteins is the main culprit suspected to be behind the development of Alzheimer's disease (AD). In this study, Aß interactions with the novel two-dimensional (2D) covalent organic frameworks (COFs) as therapeutic options for avoiding ß-amyloid aggregation have been investigated. The results from multi-scale atomistic simulations suggest that amine-functionalized COFs with a large surface area (more than 1000 m2 /gr) have the potential to prevent Aß aggregation. Gibb's free energy analysis confirmed that COFs could prevent protofibril self-assembly in addition to inhibiting ß-amyloid aggregation. Additionally, it was observed that the amine functional group and high contact area could improve the inhibitory effect of COFs on Aß aggregation and enhance the diffusivity of COFs through the blood-brain barrier (BBB). In addition, microsecond coarse-grained (CG) simulations with three hundred amyloids reveal that the presence of COFs creates instability in the structure of amyloids and consequently prevents the fibrillation. These results suggest promising applications of engineered COFs in the treatment of AD and provide a new perspective on future experimental research.

Molecular insight into optimizing the N- and P-doped fullerenes for urea removal in wearable artificial kidneys.

Urea is the result of the breakdown of proteins in the liver, the excess of which circulates in the blood and is adsorbed by the kidneys. However, in the case of kidney diseases, some products, specifically urea, cannot be removed from the blood by the kidneys and causes serious health problems. The end-stage renal disease (ESRD) patients are not able to purify their blood, which endangers their life. ESRD patients require dialysis, a costly and difficult method of urea removal from the blood. Wearable artificial kidneys (WAKs) are consequently designed to remove the waste from blood. Regarding the great amount of daily urea production in the body, WAKs should contain strong and selective urea adsorbents. Fullerenes-which possess fascinating chemical properties-have been considered herein to develop novel urea removal adsorbents. Molecular dynamics (MD) has enabled researchers to study the interaction of different materials and can pave the way toward facilitating the development of wearable devices. In this study, urea adsorption by N-doped fullerenes and P-doped fullerenes were assessed through MD simulations. The urea adsorption was simulated by five samples of fullerenes, with phosphorous and different nitrogen dopant contents. For comparing the urea adsorption capacity in the performed simulations, detailed characteristics-including the energy analysis, radius of gyration, radial distribution function (RDF), root-mean-square fluctuation (RMSD), and H-bond analyses were investigated. It had been determined that the fullerene containing 8% nitrogen-with the highest reduction in the radius of gyration, the maximum RDF, a high adsorption energy, and a high number of hydrogen bonds-adsorbs urea more efficiently.

An insight into the role of riboflavin ligand in the self-assembly of poly(lactic-co-glycolic acid)-based nanoparticles - a molecular simulation and experimental approach.

Nanoparticles (NPs) used for targeted delivery purposes are rapidly gaining importance in diagnostic and therapeutic fields. These agents have been studied extensively so far to reveal their optimal physicochemical properties including the effects of ligands and their density on the surface of NPs. This article was conducted through a computational approach (all-atom molecular dynamics simulations) to predict the stability of NPs based on a poly-lactic-co-glycolic acid (PLGA) hydrophobic core with a poly-ethylene glycol (PEG) hydrophilic shell and varying numbers of riboflavin (RF) molecules as ligands. Depending on the molecular weight of the polymers, the most stable composition of NPs was achieved at 20 wt% and 10 wt% PLGA-PEG-RF for PLGA3kDa-PEG2kDa and PLGA4.5kDa-PEG2kDa polymers, respectively. According to the simulations, riboflavin molecules were located on the surface of the NPs, which would indicate that riboflavin-bound PLGA-PEG NPs could be efficiently utilized for active targeting purposes. To scrutinize the simulation results, NPs with riboflavin ligands were synthesized and put into in vitro experiments. Outstandingly, the empirical outcomes revealed that the hydrodynamic sizes of NPs also met minimum points at 20 and 10 wt% for PLGA3kDa-PEG2kDa and PLGA4.5kDa-PEG2kDa, respectively. Moreover, similar trends in the gyration radius as a function of riboflavin content were observed in the simulation analysis and the experimental results, which would indicate that the method of molecular dynamics (MD) simulation is a reliable mathematical technique and could be applied for predicting the physicochemical properties of NPs.

Engineering the pH-Sensitivity of the Graphene and Carbon Nanotube Based Nanomedicines in Smart Cancer Therapy by Grafting Trimetyl Chitosan.

PURPOSE: The aim of this study was to introduce a smart and responsive drug carrier for Doxorubicin (DOX) and Paclitaxel (PAX) for desirable therapeutic application. METHOD: Loading and releasing of DOX and PAX from smart and pH-sensitive functionalized single-walled carbon nanotube (SWCNTs) and graphene carriers have been simulated by molecular dynamics. The influences of chitosan polymer on proposed carriers have been studied, and both carriers were functionalized with carboxyl groups to improve the loading and releasing properties of the drugs. RESULTS: The results showed that DOX could be well adsorbed on both functionalized SWCNTs and graphene. In contrast, there was a weak electrostatic and Van der Waals interaction between both these drugs and carriers at cancerous tissues, which is highly favorable for cancer therapy. Adding trimethyl chitosan (TMC) polymer to carriers facilitated DOX release at acidic tissues. Furthermore, at blood pH, the PAX loaded on the functionalized SWCNTs carrier represented the highest dispersion of the drug while the DOX-graphene showed the highest concentration of the drug at a point. In addition, the mean-square displacement (MSD) results of PAX-graphene indicated that the PAX could be adsorbed quickly and be released slowly. Finally, functionalized graphene-TMC-PAX is a smart drug system with responsive behavior and controllable drug release, which are essential in cancer therapy. CONCLUSION: Simultaneous application of the carboxyl group and TMC can optimize the pH sensitivity of the SWCNTs and graphene to prepare a novel and smart drug carrier for cancer therapy.

Potential therapeutic options for celiac Disease: An update on Current evidence from Gluten-Free diet to cell therapy.

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment.

Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine.

The utilization of growth factors in the process of tissue regeneration has garnered significant interest and has been the subject of extensive research. However, despite the fervent efforts invested in recent clinical trials, a considerable number of these studies have produced outcomes that are deemed unsatisfactory. It is noteworthy that the trials that have yielded the most satisfactory outcomes have exhibited a shared characteristic, namely, the existence of a mechanism for the regulated administration of growth factors. Despite the extensive exploration of drug delivery vehicles and their efficacy in delivering certain growth factors, the development of a reliable predictive approach for the delivery of delicate growth factors like Vascular Endothelial Growth Factor (VEGF) remains elusive. VEGF plays a crucial role in promoting angiogenesis; however, the administration of VEGF demands a meticulous approach as it necessitates precise localization and transportation to a specific target tissue. This process requires prolonged and sustained exposure to a low concentration of VEGF. Inaccurate administration of drugs, either through off-target effects or inadequate delivery, may heighten the risk of adverse reactions and potentially result in tumorigenesis. At present, there is a scarcity of technologies available for the accurate encapsulation of VEGF and its subsequent sustained and controlled release. The objective of this review is to present and assess diverse categories of VEGF administration mechanisms. This paper examines various systems, including polymeric, liposomal, hydrogel, inorganic, polyplexes, and microfluidic, and evaluates the appropriate dosage of VEGF for multiple applications.

Biomaterial-based delivery platforms for transdermal immunotherapy.

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

Recent Advances In the development of enzymatic paper-based microfluidic biosensors.

Using microfluidic paper-based analytical devices has attracted considerable attention in recent years. This is mainly due to their low cost, availability, portability, simple design, high selectivity, and sensitivity. Owing to their specific substrates and catalytic functions, enzymes are the most commonly used bioactive agents in µPADs. Enzymatic µPADs are various in design, fabrication, and detection methods. This paper provides a comprehensive review of the development of enzymatic µPADs by considering the methods of detection and fabrication. Particularly, techniques for mass production of these enzymatic µPADs for use in different fields such as medicine, environment, agriculture, and food industries are critically discussed. This paper aims to provide a critical review of µPADs and discuss different fabrication methods as the central parts of the µPADs production categorized into printable and non-printable methods. In addition, state-of-the-art technologies such as fully printed enzymatic µPADs for rapid, low-cost, and mass production and improvement have been considered.

3D Printing of Dental Prostheses: Current and Emerging Applications.

Revolutionary fabrication technologies such as three-dimensional (3D) printing to develop dental structures are expected to replace traditional methods due to their ability to establish constructs with the required mechanical properties and detailed structures. Three-dimensional printing, as an additive manufacturing approach, has the potential to rapidly fabricate complex dental prostheses by employing a bottom-up strategy in a layer-by-layer fashion. This new technology allows dentists to extend their degree of freedom in selecting, creating, and performing the required treatments. Three-dimensional printing has been narrowly employed in the fabrication of various kinds of prostheses and implants. There is still an on-demand production procedure that offers a reasonable method with superior efficiency to engineer multifaceted dental constructs. This review article aims to cover the most recent applications of 3D printing techniques in the manufacturing of dental prosthetics. More specifically, after describing various 3D printing techniques and their advantages/disadvantages, the applications of 3D printing in dental prostheses are elaborated in various examples in the literature. Different 3D printing techniques have the capability to use different materials, including thermoplastic polymers, ceramics, and metals with distinctive suitability for dental applications, which are discussed in this article. The relevant limitations and challenges that currently limit the efficacy of 3D printing in this field are also reviewed. This review article has employed five major scientific databases, including Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus, with appropriate keywords to find the most relevant literature in the subject of dental prostheses 3D printing.

Effect of ligand conjugation site on the micellization of Bio-Targeted PLGA-Based nanohybrids: A computational biology approach.

In this study, the effect of ligand binding position on the polymeric nanoparticles (NPs) is based on poly(lactic-co-glycolic acid) (PLGA) with two different polymer chain length at the atomistic level was presented. We explored the conjugation of riboflavin (RF) ligand from the end of the ribityl chain (N-10) to the polymer strands as well as from the amine group on the isoalloxazine head (N-3). The energy interactions for all samples revealed that the NPs containing ligands from N-10 positions have higher total attraction energies and lower stability in comparison with their peers conjugated from N-3. As NPs containing RF conjugated from N-3 exhibit the lower energy level with 20% and 10% of RF-containing composition for lower and higher. The introduction of RF from the N-10 position in any composition has increased the energy level of nanocarriers. The results of Gibb's free energy confirm the interatomic interaction energies trend where the lowest Gibbs free energy level for N-3 NPs occurs at 20 and 10% of RF-containing polymer content for PLGA10- and PLGA11- based NPs. Furthermore, with N-10 samples based on both polymers, non-targeted models form the stablest particles in each category. These findings are further confirmed with molecular docking analysis which revealed affinity energy of RF toward polymer chain from N-3 and N-10 are -981.57 kJ/mole and -298.23 kJ/mole, respectively. This in-silico study paves the new way for molecular engineering of the bio-responsive PLGA-PEG-RF micelles and can be used to nanoscale tunning of smart carriers used in cancer treatment.Communicated by Ramaswamy H. Sarma.

Rare Earth Elements Recovery Using Selective Membranes via Extraction and Rejection.

Recently, demands for raw materials like rare earth elements (REEs) have increased considerably due to their high potential applications in modern industry. Additionally, REEs' similar chemical and physical properties caused their separation to be difficult. Numerous strategies for REEs separation such as precipitation, adsorption and solvent extraction have been applied. However, these strategies have various disadvantages such as low selectivity and purity of desired elements, high cost, vast consumption of chemicals and creation of many pollutions due to remaining large amounts of acidic and alkaline wastes. Membrane separation technology (MST), as an environmentally friendly approach, has recently attracted much attention for the extraction of REEs. The separation of REEs by membranes usually occurs through three mechanisms: (1) complexation of REE ions with extractant that is embedded in the membrane matrix, (2) adsorption of REE ions on the surface created-active sites on the membrane and (3) the rejection of REE ions or REEs complex with organic materials from the membrane. In this review, we investigated the effect of these mechanisms on the selectivity and efficiency of the membrane separation process. Finally, potential directions for future studies were recommended at the end of the review.

Mechanism Understanding of Li-ion Separation Using A Perovskite-Based Membrane.

Lithium ions play a crucial role in the energy storage industry. Finding suitable lithium-ion-conductive membranes is one of the important issues of energy storage studies. Hence, a perovskite-based membrane, Lithium Lanthanum Titanate (LLTO), was innovatively implemented in the presence and absence of solvents to precisely understand the mechanism of lithium ion separation. The ion-selective membrane's mechanism and the perovskite-based membrane's efficiency were investigated using Molecular Dynamic (MD) simulation. The results specified that the change in the ambient condition, pH, and temperature led to a shift in LLTO pore sizes. Based on the results, pH plays an undeniable role in facilitating lithium ion transmission through the membrane. It is noticeable that the hydrogen bond interaction between the ions and membrane led to an expanding pore size, from (1.07 Å) to (1.18-1.20 Å), successfully enriching lithium from seawater. However, this value in the absence of the solvent would have been 1.1 Å at 50 °C. It was found that increasing the temperature slightly impacted lithium extraction. The charge analysis exhibited that the trapping energies applied by the membrane to the first three ions (Li+, K+, and Na+) were more than the ions' hydration energies. Therefore, Li+, K+, and Na+ were fully dehydrated, whereas Mg2+ was partially dehydrated and could not pass through the membrane. Evaluating the membrane window diameter, and the combined effect of the three key parameters (barrier energy, hydration energy, and binding energy) illustrates that the required energy to transport Li ions through the membrane is higher than that for other monovalent cations.

In vitro scolicidal effect of Calendula officinalis, Artemisia dracunculus, Artemisia absinthium, and Ferula assafoetida extracts against hydatid cyst protoscolices.

Echinococcus granulosus is the etiologic agent of cystic echinococcosis. Numerous research studies have been conducted on natural scolicidal agents to inactivate protoscolices during surgery. This study was undertaken to compare the in vitro scolicidal effects of hydroalcoholic extracts of Calendula officinalis, Artemisia dracunculus, Artemisia absinthium and Ferula assafoetida. The scolicidal activities of the extracts were tested at different concentrations following incubation periods of 10, 30 and 60 min. The chemical composition of the hydroalcoholic extracts were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The major chemical components of C. officinalis, A. dracunculus, A. absinthium and F. assafoetida were identified as n-Docosane (14.17%), 2H-1-benzopyran-2-one, 7-methoxy (54.96%), n-Docosane (9.72%) and 2-methoxy-3-methyl-butyric acid, methyl ester (13.9%), respectively. The results showed that the hydroalcoholic extracts of A. absinthium and F. assafoetida at a concentration of 250 mg/ml resulted in killing 100% of the protoscolices at 60 minutes, while the concentration of 250 mg/ml of hydroalcoholic extract of C. officinalis and A. dracunculus resulted in killing 42.33% and 65.67%, respectively. The findings of the present study showed that A. absinthium and F. assafoetida have potent scolicidal effects. However, additional in vivo studies are required to confirm the efficacy of these plant-derived extracts against hydatid cyst for their clinical use.

Novel bioengineered MBenes for the treatment of Alzheimer's disease: An in-Sillico study.

Alzheimer's disease is a neurodegenerative disease caused by the deposition and accumulation of amyloid-ß (Aß) peptides in the brain neurons. Current medications are not a definitive cure for this disease, but they can hamper the signs and symptoms of Alzheimer's disease. Therefore, prevention is the best way to deal with this disease. In this study, the novel structures based on MBenes (such as Cd2B, Mo2B, Cu2B, and Ta2B) are proposed to prevent amyloid-ß accumulation in Alzheimer's disease. Regarding the remarkable MBene properties such as tunability, biocompatibility, and low manufacturing cost, the effect of these structures on amyloid-ß deformation was explored using molecular dynamics simulation. To provide an atomic analysis of Beta-amyloid behavior in the presence of these structures, the compaction, contact area, and stability of Beta-amyloid were investigated. The results indicated the satisfactory performance of MBenes on the destabilization of amyloid-ß structures. Moreover, given the higher interactions between Cd2B and amyloid-ß, the instability, compaction, and the contact area of amyloid-ß particles were investigated in this complex. The findings confirmed Cd2B as the best structure to prevent amyloid-ß accumulation. The results of this investigation paved the way for the development of these structures as a medicinal agent to prevent Alzheimer's disease.

In-silico study on viability of MXenes in suppressing the coronavirus infection and distribution.

Herein, based on the paramount importance of combating emerging diseases, through employing a detailed in-silico study, the possibility of using MXenes in suppressing the coronavirus infection was elucidated. To this end, first, interactions of MXene nanosheets (Mn2C, Ti2C, and Mo2C) and spike protein (SP), the main infecting portion of the COVID-19, were investigated. It was found that the modeled MXenes were effective in attracting the SP, so that they can be exploited in filtering the coronavirus. In addition, the effect of the MXenes on the SP structure was assessed which demonstrated that the secondary structure of the SP could be changed. Therefore, the post-interactions of the SP/ACE2 (receptor of coronavirus in the body) could be interrupted, declaring the lower chance of coronavirus infecting. The in-silico studies revealed that the MXenes not only can be used to adsorb and hinder the distribution of the coronavirus but also affect the SP structure and the SP/ACE2 interactions to interrupt the COVID-19 threat. Therefore, MXenes can be exploited with simultaneous roles in physical inhibition and reactive weakening of the COVID-19. In this regard, the Mn2C nanosheet was well suited, which is suggested as a promising candidate to combat the coronavirus.

Nanoscale aggregation of doxorubicin-short peptide conjugates for enzyme-responsive delivery with various MOF carriers: In-silico steps towards smart cancer chemotherapy.

Drug conjugation with enzyme-sensitive peptides is one of the innovative smart delivery systems for cancer therapy. This delivery method has some advantages, such as lowering side effects and increasing treatment selectivity. Herein, two conjugates of doxorubicin and small peptide are designed that are sensitive to Cathepsin B, a tumor homing enzyme. The formation of nanoparticles at three different numbers of drug peptide prodrugs (including 30, 50, and 70 prodrugs) was studied. In addition, three metal-organic frameworks (MOF) nanocarriers, including Zeolitic Imidazolate Frameworks (ZIF), Universitetet I Oslo MOF (UIO-66), and MOF of Hong Kong University of Science and Technology (HKUST-1), were used to increase the resistance of the prodrugs to decomposition during blood flow circulation. Then, the interactions between doxorubicin's prodrug and different MOFs were investigated. Furthermore, the impact of microfluidics on nanoparticle interactions was studied. Molecular dynamic simulation was used to investigate thermodynamic and conformational parameters. The results showed that the concentration of doxorubicin prodrugs affected cluster formation. Moreover, based on Gibb's free energy analysis, the interaction of these prodrugs with various types of MOFs revealed more spontaneous interactions in microfluidic modeling conditions. ZIF had the best and most stable interactions with the prodrugs in bulk and microfluidic modeling. As a result, the best and most stable state was associated with a lower concentration of these prodrugs with ZIF in the microfluidic condition.