Advancements in Aptamer-Driven DNA Nanostructures for Precision Drug Delivery.

DNA nanostructures exhibit versatile geometries and possess sophisticated capabilities not found in other nanomaterials. They serve as customizable nanoplatforms for orchestrating the spatial arrangement of molecular components, such as biomolecules, antibodies, or synthetic nanomaterials. This is achieved by incorporating oligonucleotides into the design of the nanostructure. In the realm of drug delivery to cancer cells, there is a growing interest in active targeting assays to enhance efficacy and selectivity. The active targeting approach involves a "key-lock" mechanism where the carrier, through its ligand, recognizes specific receptors on tumor cells, facilitating the release of drugs. Various DNA nanostructures, including DNA origami, Tetrahedral, nanoflower, cruciform, nanostar, nanocentipede, and nanococklebur, can traverse the lipid layer of the cell membrane, allowing cargo delivery to the nucleus. Aptamers, easily formed in vitro, are recognized for their targeted delivery capabilities due to their high selectivity for specific targets and low immunogenicity. This review provides a comprehensive overview of recent advancements in the formation and modification of aptamer-modified DNA nanostructures within drug delivery systems.

Metallic nanostructure-based aptasensors for robust detection of proteins.

There is a significant need for fast, cost-effective, and highly sensitive protein target detection, particularly in the fields of food, environmental monitoring, and healthcare. The integration of high-affinity aptamers with metal-based nanomaterials has played a crucial role in advancing the development of innovative aptasensors tailored for the precise detection of specific proteins. Aptamers offer several advantages over commonly used molecular recognition methods, such as antibodies. Recently, a variety of metal-based aptasensors have been established. These metallic nanomaterials encompass noble metal nanoparticles, metal oxides, metal-carbon nanotubes, carbon quantum dots, graphene-conjugated metallic nanostructures, as well as their nanocomposites, metal-organic frameworks (MOFs), and MXenes. In general, these materials provide enhanced sensitivity through signal amplification and transduction mechanisms. This review primarily focuses on the advancement of aptasensors based on metallic materials for the highly sensitive detection of protein targets, including enzymes and growth factors. Additionally, it sheds light on the challenges encountered in this field and outlines future prospects. We firmly believe that this review will offer a comprehensive overview and fresh insights into metallic nanomaterials-based aptasensors and their capabilities, paving the way for the development of innovative point-of-care (POC) diagnostic devices.

Aptamer-engineered (nano)materials for theranostic applications.

A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences. Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant literature references. This critical evaluation aims to enhance the scientific community's understanding of this field and inspire new ideas for future research endeavors.

Facilitators and barriers in the donor family interview process from the perspective of hospital staff: a cross-sectional study.

Background: Obtaining consent from potential donor families is a challenging step in the donation process and is influenced by various factors. Methods: In this cross-sectional study, we utilized a questionnaire containing 14 questions about facilitators and barriers in the family interview process. The questionnaire was distributed in March 2023 to intensive care unit (ICU) nurses who had experience with donor family interviews. We collected the opinions of these respondents on hospital performance and drew comparisons between the studied hospitals. Results: A total of 60 participating ICU nurses provided mean scores for hospital performance in family interviews of 2.60±0.84 for type I hospitals (those providing neurosurgery and trauma care) and 2.035±0.890 for type II hospitals (those without neurosurgery and trauma services; P=0.04). The mean scores for public and private hospitals were 1.86±0.86 and 2.59±0.85, respectively (P=0.008). Based on the findings, the most important facilitators were the availability of organ donation staff and access to a professional team for family discussions. Conversely, poor physician communication skills and limited communication capabilities among medical staff were identified as significant barriers. Implementation of a professional team for family interviews was found to be more critical for type II hospitals. Poor physician communication skills were a significant concern in public hospitals, while families' lack of awareness of patient prognosis emerged as a key barrier in private hospitals. Conclusions: This study highlights numerous facilitators and barriers that vary across hospitals. Addressing these issues individually and developing tailored plans to enhance hospital performance in interviewing donor families is essential.

Stimuli-responsive biomaterials: smart avenue toward 4D bioprinting.

3D bioprinting is an advanced technology combining cells and bioactive molecules within a single bioscaffold; however, this scaffold cannot change, modify or grow in response to a dynamic implemented environment. Lately, a new era of smart polymers and hydrogels has emerged, which can add another dimension, e.g., time to 3D bioprinting, to address some of the current approaches' limitations. This concept is indicated as 4D bioprinting. This approach may assist in fabricating tissue-like structures with a configuration and function that mimic the natural tissue. These scaffolds can change and reform as the tissue are transformed with the potential of specific drug or biomolecules released for various biomedical applications, such as biosensing, wound healing, soft robotics, drug delivery, and tissue engineering, though 4D bioprinting is still in its early stages and more works are required to advance it. In this review article, the critical challenge in the field of 4D bioprinting and transformations from 3D bioprinting to 4D phases is reviewed. Also, the mechanistic aspects from the chemistry and material science point of view are discussed too.

A green-based approach for noninvasive skin rejuvenation: Potential application of hyaluronic acid.

Gradually, loss of skin elasticity and elastic properties occurs after 30 years of age and will be associated with several changes, including creating wrinkles, skin laxity (sagging skin), and skin blemishes. In general, people all over the world are looking for ways to keep their facial skin young over time. There are several strategies to skin rejuvenate, including invasive and non-invasive methods. However, invasive methods have less popularity than non-invasive methods due to their need for specialist physicians (medical expertise), localized neuropathic pains for patients, the prevalence and incidence of skin infections, and high-cost clinical services. In the meantime, skin hydration is one of the simplest non-invasive methods for skin rejuvenation, and HA, with anti-aging and skin collagen-stimulating properties, has been introduced as a natural skin moisturizing agent. Therefore, since this composition maintains facial skin moisture and radiance, and improves its elasticity, it has always been considered by experts and specialist physicians. On the other hand, due to its lipophilic properties, hydrophilic macromolecules containing HA cannot pass through the stratum corneum. However, they have temporary and superficial softening effects on the skin. Hence, some nanocarriers have been suggested to overcome this problem and develop the properties and positive influences of HA on skin rejuvenation. Therefore, the present study aimed to introduce some new non-invasive approaches in facial skin rejuvenation, including applying liposomes, niosomes, ethosomes, and ionic liquids, to transport HA into the inner and deeper layers of the skin, including Dermis. In this review article, we examine non-invasive methods using nanoparticles to deliver HA to the epidermis and dermis of the skin for skin rejuvenation.

Self-Healing MXene- and Graphene-Based Composites: Properties and Applications.

Today, self-healing graphene- and MXene-based composites have attracted researchers due to the increase in durability as well as the cost reduction in long-time applications. Different studies have focused on designing novel self-healing graphene- and MXene-based composites with enhanced sensitivity, stretchability, and flexibility as well as improved electrical conductivity, healing efficacy, mechanical properties, and energy conversion efficacy. These composites with self-healing properties can be employed in the field of wearable sensors, supercapacitors, anticorrosive coatings, electromagnetic interference shielding, electronic-skin, soft robotics, etc. However, it appears that more explorations are still needed to achieve composites with excellent arbitrary shape adaptability, suitable adhesiveness, ideal durability, high stretchability, immediate self-healing responsibility, and outstanding electromagnetic features. Besides, optimizing reaction/synthesis conditions and finding suitable strategies for functionalization/modification are crucial aspects that should be comprehensively investigated. MXenes and graphene exhibited superior electrochemical properties with abundant surface terminations and great surface area, which are important to evolve biomedical and sensing applications. However, flexibility and stretchability are important criteria that need to be improved for their future applications. Herein, the most recent advancements pertaining to the applications and properties of self-healing graphene- and MXene-based composites are deliberated, focusing on crucial challenges and future perspectives.

Natural resources for sustainable synthesis of nanomaterials with anticancer applications: A move toward green nanomedicine.

Today, researchers have focused on the application of environmentally-benign and sustainable micro- and nanosystems for drug delivery and cancer therapy. Compared to conventional chemotherapeutics, advanced micro- and nanosystems designed by applying abundant, natural, and renewable feedstocks have shown biodegradability, biocompatibility, and low toxicity advantages. However, important aspects of toxicological assessments, clinical translational studies, and suitable functionalization/modification still need to be addressed. Herein, the benefits and challenges of green nanomedicine in cancer nanotherapy and targeted drug delivery are cogitated using nanomaterials designed by exploiting natural and renewable resources. The application of nanomaterials accessed from renewable natural resources, comprising metallic nanomaterials, carbon-based nanomaterials, metal-organic frameworks, natural-derived nanomaterials, etc. for targeted anticancer drug delivery and cancer nanotherapy are deliberated, with emphasis on important limitations/challenges and future perspectives.

Engineered Biomimetic Membranes for Organ-on-a-Chip.

Organ-on-a-chip (OOC) systems are engineered nanobiosystems to mimic the physiochemical environment of a specific organ in the body. Among various components of OOC systems, biomimetic membranes have been regarded as one of the most important key components to develop controllable biomimetic bioanalysis systems. Here, we review the preparation and characterization of biomimetic membranes in comparison with the features of the extracellular matrix. After that, we review and discuss the latest applications of engineered biomimetic membranes to fabricate various organs on a chip, such as liver, kidney, intestine, lung, skin, heart, vasculature and blood vessels, brain, and multiorgans with perspectives for further biomedical applications.

Functionalized Silver and Gold Nanomaterials with Diagnostic and Therapeutic Applications.

The functionalization of nanomaterials with suitable capping ligands or bioactive agents is an interesting strategy in designing nanosystems with suitable applicability and biocompatibility; the physicochemical and biological properties of these nanomaterials can be highly improved for biomedical applications. In this context, numerous explorations have been conducted in the functionalization of silver (Ag) and gold (Au) nanomaterials using suitable functional groups or agents to design nanosystems with unique physicochemical properties such as excellent biosensing capabilities, biocompatibility, targeting features, and multifunctionality for biomedical purposes. Future studies should be undertaken for designing novel functionalization tactics to improve the properties of Au- and Ag-based nanosystems and reduce their toxicity. The possible release of cytotoxic radicals or ions, the internalization of nanomaterials, the alteration of cellular signaling pathways, the translocation of these nanomaterials across the cell membranes into mitochondria, DNA damages, and the damage of cell membranes are the main causes of their toxicity, which ought to be comprehensively explored. In this study, recent advancements in diagnostic and therapeutic applications of functionalized Au and Ag nanomaterials are deliberated, focusing on important challenges and future directions.

Viral and non-viral gene therapy using 3D (bio)printing.

The overall success in launching discovered drugs is tightly restricted to the high rate of late-stage failures, which ultimately inhibits the distribution of medicines in markets. As a result, it is imperative that methods reliably predict the effectiveness and, more critically, the toxicity of medicine early in the drug development process before clinical trials be continuously innovated. We must stay up to date with the fast appearance of new infections and diseases by rapidly developing the requisite vaccinations and medicines. Modern in vitro models of disease may be used as an alternative to traditional disease models, and advanced technology can be used for the creation of pharmaceuticals as well as cells, drugs, and gene delivery systems to expedite the drug discovery procedure. Furthermore, in vitro models that mimic the spatial and chemical characteristics of native tissues, such as a 3D bioprinting system or other technologies, have proven to be more effective for drug screening than traditional 2D models. Viral and non-viral gene delivery vectors are a hopeful tool for combinatorial gene therapy, suggesting a quick way of simultaneously deliver multiple genes. A 3D bioprinting system embraces an excellent potential for gene delivery into the different cells or tissues for different diseases, in tissue engineering and regeneration medicine, in which the precise nucleic acid is located in the 3D printed tissues and scaffolds. Non-viral nanocarriers, in combination with 3D printed scaffolds, are applied to their delivery of genes and controlled release properties. There remains, however, a big obstacle in reaching the full potential of 3D models because of a lack of in vitro manufacturing of live tissues. Bioprinting advancements have made it possible to create biomimetic constructions that may be used in various drug discovery research applications. 3D bioprinting also benefits vaccinations, medicines, and relevant delivery methods because of its flexibility and adaptability. This review discusses the potential of 3D bioprinting technologies for pharmaceutical studies.

Magnetic nanocomposites for biomedical applications.

Tissue engineering and regenerative medicine have solved numerous problems related to the repair and regeneration of damaged organs and tissues arising from aging, illnesses, and injuries. Nanotechnology has further aided tissue regeneration science and has provided outstanding opportunities to help disease diagnosis as well as treat damaged tissues. Based on the most recent findings, magnetic nanostructures (MNSs), in particular, have emerged as promising materials for detecting, directing, and supporting tissue regeneration. There have been many reports concerning the role of these nano-building blocks in the regeneration of both soft and hard tissues, but the subject has not been extensively reviewed. Here, we review, classify, and discuss various synthesis strategies for novel MNSs used in medicine. Advanced applications of magnetic nanocomposites (MG-NCs), specifically magnetic nanostructures, are further systematically reviewed. In addition, the scientific and technical aspects of MG-NC used in medicine are discussed considering the requirements for the field. In summary, this review highlights the numerous opportunities and challenges associated with the use of MG-NCs as smart nanocomposites (NCs) in tissue engineering and regenerative medicine.

Advances in aptamer-based drug delivery vehicles for cancer therapy.

Overall, aptamers are special classes of nucleic acid-based macromolecules that are beginning to investigate because of their capability of avidity binding to a specific target for clinical use. Taking advantage of target-specific medicine led to more effective therapeutic and limitation of side effects of drugs. Herein, we discuss several aptamers and their binding capability and capacity for selecting tumor biomarkers and usage of them as targeting ligands for the functionalization of nanomaterials. We review recent applications based on aptamers and several nanoparticles to rise efficacy and develop carrier systems such as graphene oxide, folic acid, gold, mesopores silica, and various polymers and copolymer, polyethylene glycol, cyclodextrin, chitosan. The nanocarriers have been characterized by particle size, zeta potential, aptamer conjugation, and drug encapsulation efficiency. Hydrodynamic diameter and Zeta potential can used in order to monitor aptamers' crosslinking, in-vitro drug release, intracellular delivery of nanocarriers, and cellular cytotoxicity assay. Also, they are studied for cellular uptake and internalization to types of cancer cell lines such as colorectal, breast, prostate, leukemia and etc. The results are investigated in in-vivo cytotoxicity assay and cell viability assay. Targeted cancer therapy seems a good and promising strategy to overcome the systemic toxicity of chemotherapy.

3D printing of bioactive materials for drug delivery applications.

INTRODUCTION: Three-dimensional (3D) printing, also known as additive manufacturing (AM), is a modern technique/technology, which makes it possible to construct 3D objects from computer-aided design (CAD) digital models. This technology can be used in the progress of drug delivery systems, where porosity has played important role in attaining an acceptable level of biocompatibility and biodegradability with improved therapeutic effects. 3D printing may also provide the user possibility to control the dosage of each ingredient in order to a specific purpose, and makes it probable to improve the formulation of drug delivery systems. AREAS COVERED: This article covers the 3D printing technologies, bioactive materials including natural and synthetic polymers as well as some ceramics and minerals and their roles in drug delivery systems. EXPERT OPINION: This technology is feasible to fabricate drug products by incorporating multiple drugs in different parts in such a mode that these drugs can release from the section at a predetermined rate. Furthermore, this 3D printing technology has the potential to transform personalized therapy to various age-groups by design flexibility and precise dosing. In recent years, the potential use of this technology can be realized in a clinical situation where patients will acquire individualized medicine as per their requirement.

Genetically Engineered Viral Vectors and Organic-Based Non-Viral Nanocarriers for Drug Delivery Applications.

Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems are developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli-responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic-based nanoparticles including cellulose, collagen, silk-like polymers, elastin-like protein, silk-elastin-like protein, and inorganic-based nanoparticles are discussed in detail. Afterward, viral-based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded.

Customizing nano-chitosan for sustainable drug delivery.

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article.

MIL-125-based nanocarrier decorated with Palladium complex for targeted drug delivery.

The aim of this work was to provide a novel approach to designing and synthesizing a nanocomposite with significant biocompatibility, biodegradability, and stability in biological microenvironments. Hence, the porous ultra-low-density materials, metal-organic frameworks (MOFs), have been considered and the MIL-125(Ti) has been chosen due to its distinctive characteristics such as great biocompatibility and good biodegradability immobilized on the surface of the reduced graphene oxide (rGO). Based on the results, the presence of transition metal complexes next to the drug not only can reinforce the stability of the drug on the structure by preparing π-π interaction between ligands and the drug but also can enhance the efficiency of the drug by preventing the spontaneous release. The effect of utilizing transition metal complex beside drug (Doxorubicin (DOX)) on the drug loading, drug release, and antibacterial activity of prepared nanocomposites on the P. aeruginosa and S. aureus as a model bacterium has been investigated and the results revealed that this theory leads to increasing about 200% in antibacterial activity. In addition, uptake, the release of the drug, and relative cell viabilities (in vitro and in vivo) of prepared nanomaterials and biomaterials have been discussed. Based on collected data, the median size of prepared nanocomposites was 156.2 nm, and their biological stability in PBS and DMEM + 10% FBS was screened and revealed that after 2.880 min, the nanocomposite's size reached 242.3 and 516 nm respectively. The MTT results demonstrated that immobilizing PdL beside DOX leads to an increase of more than 15% in the cell viability. It is noticeable that the AST:ALT result of prepared nanocomposite was under 1.5.

Mission impossible for cellular internalization: When porphyrin alliance with UiO-66-NH2 MOF gives the cell lines a ride.

Is it possible to accelerate cell internalization by hybridization of nanomaterials? Herein we support the realization of using metal-organic frameworks (MOFs) with the assistance of rigid porphyrin structure (H2TMP) aimed at drug loading, drug release, relative cell viability, and targeted in vitro drug delivery. There are several MOFs, i.e., UiO-66-NH2 (125 ± 12.5 nm), UiO-66-NH2 @H2TMP (160 ± 14 nm), UiO-66-NH2 @H2TMP@DOX, and UiO-66-NH2 @H2TMP@DOX@RO were synthesized and characterized applying HEK-293, HT-29, MCF-7, and MCF-10A cell lines. MTT investigations proved a significantly higher relative cell viability for H2TMP-aided leaf-extract-coated nanocarriers (above 62 % relative cell viability). Furthermore, the rigid H2TMP structure improved drug loading capacity by 24 % through an enhanced hydrogen bond, van der Waals, and π-π interactions. The in vitro targeted drug delivery experiments were conducted on HT-29 and MCF-7 cell lines. First, nanocarriers were treated with HT-29 cells, where UiO-66-NH2 @H2TMP@DOX@RO appeared as the best nanocarrier. Then, the selected nanocarrier was extracted from the HT-29 cell line and treated with the MCF-7 cell line. For the first time, the DOX remained inside the UiO-66-NH2 @H2TMP@DOX@RO after successful delivery to the HT-29 cell lines was observed on the MCF-7 cell line, and the second targeted drug delivery was performed. The results of this survey can enlighten the future ahead of cell internalization in MOF-based hybrid nanostructures.

Chemotherapeutic effects of Apigenin in breast cancer: Preclinical evidence and molecular mechanisms; enhanced bioavailability by nanoparticles.

This review highlights using nanotechnology in increasing the bioavailability of AP (Apigenin) to enhance its therapeutic efficacy in breast cancer treatment. Breast cancer is one of the most leading causes of cancer death in women both in developed and developing countries. According to several epidemiological and clinical trial studies that indicate progestin-stimulated breast cancer in post-menopausal women; it is necessary to determine compounds to suppress or attenuate the tumor-promoting effects of progestins in breast cells. For this purpose, using the natural anti-progestins, including AP compared with the chemical ones could be significantly effective due to the lack of toxicities and contradiction effects. However, AP is categorized as a Class II drug of Biopharmaceutical Classification System with low solubility in water which limited its therapeutic effects. Therefore, nanotechnology due to the presentation of remarkable properties has overcome this limitation through enhanced the solubility and bioavailability of AP. In this regard, various nanocarriers such as nanocrystals, micelles, liposomes, PLGA, etc., have highlighted the significantly increased bioavailability and therapeutic efficacy of AP. Therefore, we will focus on the anticancer effects of AP in breast cancers, including involved mechanisms, the chemistry of AP and its bioavailability, finally different nanostructure systems to enhance the bioavailability of AP.

Detection of Dopamine Receptors Using Nanoscale Dendrimer for Potential Application in Targeted Delivery and Whole-Body Imaging: Synthesis and In Vivo Organ Distribution.

Dopamine is one of the most important neurotransmitters released by neurons in the central nervous system, and a variety of neurological illnesses and mental disorders are associated with impairments in the secretion and functionality of dopamine. Dopamine, depending on the type of receptors, can act as a stimulant or an inhibitor. In this study, dendrimer-conjugated dopamine was utilized as a chelating agent for Technetium-99m to investigate the organ distribution of this compound in vivo using the single-photon emission computed tomography (SPECT) technique. For this purpose, dendrimers were synthesized using polyethylene glycol diacid and citric acid precursors, and dopamine was conjugated to the dendrimer using EDC/NHS cross-linker. The results showed no sign of toxicity of the dopamine-functionalized dendrimers on HEK-293 cell lines. The optimization of labeling conditions was conducted using the experimental design method (i.e., conjugate value, pH, and the amount of reducing agent), and then labeling efficiency was evaluated by thin-layer chromatography (TLC). Finally, the study of organ distribution in normal mice using SPECT imaging and comparing it with gene expression in different organs revealed that dopamine D1 receptors exhibited the highest accumulation in the liver and that the drug retained its specificity.