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Abstract Breast cancer, a widespread malignancy affecting women globally, often arises from mutations in estrogen/progesterone receptors. Conventional treatments like surgery, radiotherapy, and chemotherapy face limitations such as low efficacy and adverse effects. However, nanotechnology offers promise with its unique attributes like targeted delivery and controlled drug release. Yet, challenges like poor size distribution and environmental concerns exist. Biogenic nanotechnology, using natural materials or living cells, is gaining traction for its safety and efficacy in cancer treatment. Biogenic nanoparticles synthesized from plant extracts offer a sustainable and eco-friendly approach, demonstrating significant toxicity against breast cancer cells while sparing healthy ones. They surpass traditional drugs, providing benefits like biocompatibility and targeted delivery. Thus, this current review summarizes the available knowledge on breast cancer (its types, stages, histopathology, symptoms, etiology and epidemiology) with the importance of using biogenic nanomaterials as a new and improved therapy. The novelty of this work lies in its comprehensive examination of the challenges and strategies for advancing the industrial utilization of biogenic metal and metal oxide NPs. Additionally; it underscores the potential of plant-mediated synthesis of biogenic NPs as effective therapies for breast cancer, detailing their mechanisms of action, advantages, and areas for further research.

Abstract The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood–brain–barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood–brain–barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Quantum dots (QDs), also known as nanoparticle-based fluorescent probes, are luminescent semiconductor particles with a size range of 2–20 nm. The unique optical and electronic capabilities of QDs have led to expanded applications in several fields such as optoelectronics, transistors, sensors, photodetection, catalysis, and medicine. The distinct quantum effects of nanocrystals can be controlled by changing their sizes and shapes using a variety of top-down and bottom-up tactics. QDs were traditionally fabricated using complex, expensive, toxic, and aggressive chemical techniques, which limited their application in a variety of disciplines. A unique approach for the biosynthesis of nanomaterials has been devised, which employs living organisms in the synthesis process and adheres to green chemistry principles. Biogenic QDs have favorable physicochemical features, biocompatibility, and fewer cytotoxic effects as a result of using natural biomolecules and enzymatic processes for mineralization, detoxification, and nucleation of metals and nonmetals to synthesize QDs. This is the first comprehensive review of its kind that highlights the synthesis of several doped and undoped QDs, including graphene QDs, carbon dots, silicon QDs, N/S-CDs, silver-CDs, cadmium-selenium QDs, and zinc oxide QDs, exclusively using photoautotrophic algae and plants. The different plausible mechanisms behind phyco- and phyto-fabrication of QDs are also discussed in detail along with their applications that include detection of organic and inorganic compounds, degradation of hazardous dyes, free radical scavenging, antimicrobial activity, cytotoxicity and bioimaging. Thus, this review aims to give valuable insights for the rational fabrication of photoluminescent nanomaterials with tunable structural and functional properties.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Abstract There is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of bone regeneration involves the transformation of mesenchymal stromal cells into osteoblasts and the subsequent mineralization of the extracellular matrix, making up the complex mechanism of osteogenesis. Icariin’s diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, and osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known for its ability to stimulate bone formation, has been found to encourage the transformation of mesenchymal stromal cells into osteoblasts and improve the subsequent process of mineralization. Several studies have demonstrated the osteogenic effects of icariin, which can be attributed to its hormone-like function. It has been found to induce the expression of BMP-2 and BMP-4 mRNAs in osteoblasts and significantly upregulate Osx at low doses. Additionally, icariin promotes bone formation by stimulating the expression of pre-osteoblastic genes like Osx, RUNX2, and collagen type I. However, icariin needs to be effectively delivered to bone to perform such promising functions. Encapsulating icariin within nanoplatforms holds significant promise for promoting osteogenesis and bone regeneration through a range of intricate biological effects. When encapsulated in nanofibers or nanoparticles, icariin exerts its effects directly at the cellular level. Recalling that inflammation is a critical factor influencing bone regeneration, icariin's anti-inflammatory effects can be harnessed and amplified when encapsulated in nanoplatforms. Also, while cell adhesion and cell migration are pivotal stages of tissue regeneration, icariin-loaded nanoplatforms contribute to these processes by providing a supportive matrix for cellular attachment and movement. This review comprehensively discusses icariin-loaded nanoplatforms used for bone regeneration and osteogenesis, further presenting where the field needs to go before icariin can be used clinically.

Abstract Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC–MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Magnetic Resonance Imaging (MRI) is a widely established method for monitoring and diagnosing neurological diseases, including multiple sclerosis (MS). MS is a disease that continuously progresses and in due course involves the progressive atrophy of neural structures (such as brain gray and white matter) leading to debilitation. Clearly, the earlier that MS can be detected, the better the chances of eventual treatment to slow down disease progression. While conventional MRI volumetry, as a non-invasive imaging technique that measures the exact volume of different brain structures, has improved the diagnosis of brain atrophy, problems still exist. This review introduces and summarizes the seminal role that nanotechnology (in terms of novel materials for improved MS diagnosis and treatment) and artificial intelligence (in terms of enhancing images via computer algorithms and novel contrast agents) are playing in improving volumetric MRI. In doing so, this one-of-a-kind review manuscript establishes how nanotechnology and artificial intelligence is improving, and will continue to improve, volumetric MRI diagnosis and treatment of MS.

The rapid growth of various industries has led to a significant, alarming increase in recalcitrant pollutants in the environment. Hazardous dyes, heavy metals, pesticides, pharmaceutical products, and other associated polycyclic aromatic hydrocarbons (such as acenaphthene, fluorene, fluoranthene, phenanthrene, and pyrene) have posed a significant threat to the surroundings due to their refractory nature. Although activated carbon has been reported to be an adsorbent for removing contaminants from wastewater, it has its limitations. Hence, this review provides an elaborate account of converting agricultural waste into biochar with nanotextured surfaces that can serve as low-cost adsorbents with promising pollutant-removing properties. A detailed mechanism rationalized that this strategy involves the conversion of agrowaste to promising adsorbents that can be reduced, reused, and recycled. The potential of biowaste-derived biochar can be exploited for developing biofuel for renewable energy and also for improving soil fertility. This strategy can provide a solution to control greenhouse gas emissions by preventing the open burning of agricultural residues in fields. Furthermore, this serves a dual purpose for environmental remediation as well as effective management of agricultural waste rich in both organic and inorganic components that are generated during various agricultural operations. In this manner, this review provides recent advances in the use of agrowaste-generated biochar for cleaning the environment.

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5–8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow’s butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

Cardiovascular diseases bear strong socioeconomic and ecological impact on the worldwide healthcare system. A large consumption of goods, use of polymer-based cardiovascular biomaterials, and long hospitalization times add up to an extensive carbon footprint on the environment often turning out to be ineffective at healing such cardiovascular diseases. On the other hand, cardiac cell toxicity is among the most severe but common side effect of drugs used to treat numerous diseases from COVID-19 to diabetes, often resulting in the withdrawal of such pharmaceuticals from the market. Currently, most patients that have suffered from cardiovascular disease will never fully recover. All of these factors further contribute to the extensive negative toll pharmaceutical, biotechnological, and biomedical companies have on the environment. Hence, there is a dire need to develop new environmentally-friendly strategies that on the one hand would promise cardiac tissue regeneration after damage and on the other hand would offer solutions for the fast screening of drugs to ensure that they do not cause cardiovascular toxicity. Importantly, both require one thing–a mature, functioning cardiac tissue that can be fabricated in a fast, reliable, and repeatable manner from environmentally friendly biomaterials in the lab. This is not an easy task to complete as numerous approaches have been undertaken, separately and combined, to achieve it. This review gathers such strategies and provides insights into which succeed or fail and what is needed for the field of environmentally-friendly cardiac tissue engineering to prosper.

Abstract Designing and synthesizing biodegradable drug delivery systems are key research areas in biomedical nanotechnology. Here, we report the development of biodegradable magnesium-layered hydroxide (MgLH) based nanodelivery systems using magnesium oxide (MgO) as the precursor by a precipitation method. The designed nanocarrier does not contain any trivalent metal ions, which are most commonly used for the synthesis of layered double hydroxides (LDHs). The designed delivery system was characterized in detail using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and inductively coupled plasma (ICP) analyses. The anti-tuberculosis (anti-TB) drug pyrazinamide (PZA) was successfully intercalated into interlayer galleries of MgLH, resulting in the formation of the nanocomposite, PZA-MgLH, having an average size of about 107 ± 24 nm with a uniform circular shape. The in vitro release of PZA in a human body simulated phosphate buffer saline (PBS) solution was sustained (i.e., almost 66 h) and followed a pseudo-secondorder kinetic model. Moreover, the designed nanodelivery system was found to be highly biocompatible with human normal lung cells (MRC-5) and with 3T3 fibroblast cells as controls for 24 and 48 h. Lastly, the PZA-MgLH nanocomposite showed good anti-tuberculosis activity against Mycobacterium tuberculosis and both the PZA-MgLH nanocomposite and its released free drug PZA showed antibacterial activity against tested Gram-positive and Gram-negative bacteria with percentage inhibition ranging from 5.6% to 68% against S. aureus, E. coli, and P. aeruginosa for the PZA free drug, and 32% to 32.5% against E. coli for the PZA-MgLH nanocomposite. In summary, the present results provide significant evidence that the designed nanodelivery system can be used for the delivery of PZA and, thus, should be investigated further for a wide range of anti-TB applications.

Abstract The safe and targeted delivery of pharmaceutical formulations has relied extensively on synthetic chemistry and other physicochemical approaches. The research paradigm is now especially changing towards green (or environmentally friendly) approaches, and several biopolymer‐based nanocarriers are marked as emerging nanomedicine tools. These have been developed to overcome problems with conventional drug carriers, which induce severe side effects, especially due to non‐specificity with detrimental effects on non‐targeted normal healthy cells. In addition, the phagocytosis of classic nanoparticles (NPs) and their degradation associated with the formation of oxygen radicals by the immune system are significant barriers for drug delivery. In this regard, protein nanocarriers appear as a promising approach to escape unwanted immune reactions. Moreover, these protein‐based NPs are generally non‐toxic, biodegradable, and even cost‐effective. As a less appreciated advantage, the surface properties of proteins are easily modified. There are, however, several challenges and limiting choices to make when choosing the type of modification to enable effective drug delivery. Here, we shed light on the role of protein nanocarriers for enhancing the bioavailability of different anti‐inflammatory drugs, including better macrophage targeting and overcoming biological barriers. This insight helps one to understand their broad utility in the treatment of inflammatory diseases and bridges the gap between naturaltherapeutic products and nanotechnology‐based delivery approaches, creating perhaps an optimal blend to meet some of our most persistent healthcare problems.

Introduction: The non-specific delivery of drugs to tissues is one of the major problems in traditional chemotherapy that creates problems, importantly cytotoxicity to healthy cells. A drug carrier can be designed and synthesized using a variety of techniques that allow the drug to be delivered to a specific target site with sustained release. Here, we designed novel polymer-encapsulated magnetic microspheres as drug carriers that enable site-specific and controlled drug delivery to improve therapeutic outcomes. In our study, we developed a novel emulsion-based technique to produce curcumin-loaded polymer-encapsulated magnetic microspheres. Methods: The method involves the preparation of a binary emulsion system (water-in-oil-in-water (W1-O-W2) followed by evaporation of the continuous aqueous phase to produce magnetic polylactic acid (PLA) microspheres containing curcumin (CUR) and ferrite magnetic nanoparticles (FA-MMS). The construction of the prepared Ferrite@FA-CUR-PLA-MMS drug carrier was characterized using various spectroscopic and microscopic techniques. Results: The prepared Ferrite@FA-CUR-PLA-MMS drug displayed a unique and constant pH-dependent curcumin release from the drug carriers. The cytotoxicity determination of the Ferrite@FA-CUR-PLA-MMS drug by MTT assays confirmed a low cytotoxic effect on A549 and Hela cancer cells with a minimum inhibitory concentration (IC50) for A549 cells at 15 µg/ml for 24 h and for Hela cells, the IC50 value was 12 µg/ml. After 24 h, the IC50 values for A549 and Hela cancer cells were found to be 10.2 µg/ml and 8.8 µg/ml, respectively. After 10 days of incubation, the drug exhibited total destruction of the A549 and Hela cancer cells. Discussion: Our findings have greater implications for the potential use of magnetic nanoparticles in cancer chemotherapy. Further investigations on the application of this drug delivery system could be extended to the site-specific and controlled delivery of other cancer chemotherapeutic agents.

Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3–Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3–Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

Abstract Here, molecular dynamics (MD) simulations were employed to explore the self-assembly of polymers and docetaxel (DTX) as an anticancer drug in the presence of nitrogen, phosphorous, and boron-nitrogen incorporated graphene and fullerene. The electrostatic potential and the Gibbs free energy of the self-assembled materials were used to optimize the atomic doping percentage of the N- and P-doped formulations at 10% and 50%, respectively. Poly lactic-glycolic acid (PLGA)- polyethylene glycol (PEG)-based polymeric nanoparticles were assembled in the presence of nanocarbons in the common (corresponding to the bulk environment) and interface of organic/aqueous solutions (corresponding to the microfluidic environment). Assessment of the modeling results (e.g., size, hydrophobicity, and energy) indicated that among the nanocarbons, the N-doped graphene nanosheet in the interface method created more stable polymeric nanoparticles (PNPs). Energy analysis demonstrated that doping with nanocarbons increased the electrostatic interaction energy in the self-assembly process. On the other hand, the fullerene-based nanocarbons promoted van der Waals intramolecular interactions in the PNPs. Next, the selected N-doped graphene nanosheet was utilized to prepare nanoparticles and explore the physicochemical properties of the nanosheets in the permeation of the resultant nanoparticles through cell-based lipid bilayer membranes. In agreement with the previous results, the N-graphene assisted PNP in the interface method and was translocated into and through the cell membrane with more stable interactions. In summary, the present MD simulation results demonstrated the success of 2D graphene dopants in the nucleation and growth of PLGA-based nanoparticles for improving anticancer drug delivery to cells, establishing new promising materials and a way to assess their performance that should be further studied.

Abstract Molecular imprinting (MI) is a technique that creates a template of a molecule for improving complementary binding sites in terms of size and shape to a peptide, protein, bacteria, mammalian cell, or virus on soft materials (such as polymers, hydrogels, or self-assembled materials). MI has been widely investigated for over 90 years in various industries but is now focused on improved tissue engineering, regenerative medicine, drug delivery, sensors, diagnostics, therapeutics and other medical applications. Molecular targets that have been studied so far in MI include those for the major antigenic determinants of microorganisms (like bacteria or viruses) leading to innovations in disease diagnosis via solid-phase extraction separation and biomimetic sensors. As such, although not widely investigated yet, MI demonstrates much promise for improving the detection of and treatment for the current Coronavirus Disease of 2019 (COVID-2019) pandemic as well as future pandemics. In this manner, this review will introduce the numerous applications of MI polymers, particularly using proteins and peptides, and how these MI polymers can be used as improved diagnostic and therapeutic tools for COVID-19. Graphic Abstract

Cases of the Marburg virus have started to rise and there is an urgent need to find a cure or therapy before another world-wide quarantine is introduced. There are no treatments for this virus other than giving infected people plenty of water due to excessive bleeding. Here, we report a growing strategy to use self-assembled nano peptides to attach to and inhibit viruses from replicating. Specifically, we summarize the research of others who have used this approach for Ebola, SARS-CoV-2, and other viruses and even provide our own eight octapeptides that show interference with the Marburg virus and viral RNA. These peptides self-assemble in a similar matter as the virus itself self-assembling along the viral RNA. These eight octapeptides (KLVVGDRAS, GDRASIEK, EILLAREL, ARELTLRK, FLSFCSLF, CSLFLPKL, WITWMTIW, and MTIWIPEI) were selected based on a conserved nanoparticle core sequence containing both N- and C- terminal lobes. The total atomic contact energy of these peptides as determined through computational modeling are: -110.97501, -118.57263, -99.82477, -120.60967, -17.14494, -52.11275, -14.02828, and -45.64357 kcal/mol, respectively. Collectively with results from other researchers who have designed self-assembled nano peptides to passivate other viruses, this report summarizes the strong attraction that can occur between candidate peptides and the Marburg virus. Further in vitro and in vivo studies of these peptides are needed to fully evaluate their efficacy to treat the Marburg virus, but clearly this review article demonstrates that there is a strong future for using self-assembled nano peptides to prevent and treat viral outbreaks.

New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer (NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor (CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities, starting with the U.S. Food and Drug Administration (FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.

The SARS-CoV-2 Omicron variant is called a “variant of concern” (VOC) which has spread all over the world at a faster rate than even the first SARS-CoV-2 outbreak despite travel restrictions. In order to combat the health consequences from a SARS-CoV-2 Omicron variant infection, the objective of the present in vitro study was to develop self-assembled nano peptides to attach to the virus and inhibit its attachment and entry into mammalian cells for replication. For this purpose, two amphipathic peptides containing hydrophobic and hydrophilic peptides and an unnatural amino acid (such as 2-aminoisobutyric acid (U)) were designed to attach to the less mutated virus envelope rather than more frequently mutated S-protein region: NapFFTLUFLTUTEKKKK and NapFFMLUFLMUMEKKKK. These peptides were synthesized using the solid phase peptide synthesis method and were characterized for mammalian cell infection using well-established pseudo virus assays. In vitro results showed that the two self-assembled nano peptides significantly inhibited the ability of the SARS-CoV-2 Omicron variant virus to infect mammalian cells and replicate with IC50 values of 0.5 and 360 mg/ml for NapFFTLUFLTUTEKKKK and NapFFMLUFLMUMEKKKK, respectively. Most impressively, 1 mg/ml of NapFFTLUFLTUTEKKKK resulted in a 2 log reduction in pseudovirus replication after just 15 min at a viral load of 106 copies/ml. Results further confirmed that the peptides continued to passivate the SARS-CoV-2 Omicron variant for up to one week and were stable in cell culture media before being added to the virus. Mechanistically, in vitro results showed selective binding of the peptides to the SARS-CoV-2 Omicron variant envelop protein over the more frequently mutated spike protein up to one week demonstrating the stability of the peptides. Cytotoxicity studies with fibroblasts also showed no toxicity when exposed to the peptides for 72 h. In summary, the present results strongly suggest that the two peptides developed in this study should be further researched for a wide range of anti-SARS-CoV-2 virus applications, including the present Omicron and future mutations.

Afewerki et al. employ integrated electrospinning, plasma treatment and direct surface modification strategy to engineer multifunctional bactericidal nanofibers for use in hernia repair. In a mouse model, they demonstrate that these nanofibers display good biological performance with low inflammatory response, good biodegradation and optimal collagen and blood vessel formation and tissue growth.

The production of scaffolds using a combination of synthetic and natural polymers has been widely studied for numerous tissue engineering applications, as it results in a material with superior properties, combining availability, processability, and the strength and resilience of synthetic polymers with the high biocompatibility of natural polymers. In the present study, fibrous membranes composed of polyurethane and gelatin were fabricated by rotary jet spinning and were posteriorly characterized for their morphological, chemical composition, thermal stability, hydrophilic properties as well as cell viability. Viscosity measurements were taken to achieve the critical concentration of the polymeric solution (9% wt/v), and the production of fibers at different rotational speeds (3000, 6000, 9000 and 12,000 rpm) was performed to evaluate the effect of rotational speed on fiber diameter and morphology, as observed in scanning electron microscopy analyses. Continuous and bead-free fibers were achieved at 6000 rpm with average diameter of 12.5 μm. Chemical composition characterization showed the characteristic peaks of both polymers and the absence of the organic solvent, while the addition of gelatin did not affect the thermal stability of the membrane (up to 314 °C). Additionally, the water contact angle proved the membrane hydrophilic nature (81.3°). Cell viability assays exhibited cytocompatibility with endothelial cells for 24, 48 and 72 h. The results demonstrate that the PU–Gel combination with the rotary jet spinning process is promising to obtain low-cost scaffolds with interesting properties for numerous tissue engineering applications, and, thus, should be further studied.

Radiotherapy as an anti-tumor treatment can stimulate the immune system. However, irradiated tumor cells express CD47 to escape the anti-tumor immune response. Anti- CD47 Immunotherapy is a possible way to tackle this problem. This study evaluated the effect of single high dose radiotherapy combined with an anti-CD47 monoclonal antibody (αCD47 mAb) in CT26 tumor-bearing BALB/c mice. We assessed the tumors volume and survival in mice 60 days after tumor implantation. Also, immune cell changes were analyzed by flow cytometry in tumors, lymph nodes, and spleen. Combination therapy enhanced the anti-tumor response in treated mice by increasing CD8+ T cells and M1 macrophages and decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME). Also, our results showed that combination therapy increased survival time in mice compared to other groups. Furthermore, tumor volumes remarkably decreased in mice that received a single high dose RT plus αCD47 mAb. In conclusion, we showed that combining RT and αCD47 mAb improved the immune cell population in TME, regressed tumor growth, and increased survival in tumor-bearing mice.

Strategies for the production of new nanocomposites that promote bone tissue regeneration are important, particularly those that enhance the osteoinduction of hydroxyapatite in situ. Here, we studied and report the synthesis of nanohydroxyapatite and titanate nanotube (nHAp/TiNT) composites formulated at different concentrations (1, 2, 3, and 10 wt % TiNT) by means of a wet aqueous chemical reaction. The addition of TiNT affects the morphology of the nanocomposites, decreasing the average crystallite size from 54 nm (nHAp) to 34 nm (nHAp/TiNT10%), while confirming its interaction with the nanocomposite. The crystallinity index (CI) calculated by Raman spectroscopy and XRD showed that the values decreased according to the increase in TiNT concentration, which confirmed their addition to the structure of the nanocomposite. SEM images showed the presence of TiNTs in the nanocomposite. We further verified the potential cytotoxicity of murine fibroblast cell line L929, revealing that there was no remarkable cell death at any of the concentrations tested. In vivo regenerative activity was performed using oophorectomized animal (rat) models organized into seven groups containing five animals each over two experimental periods (15 and 30 days), with bone regeneration occurring in all groups tested within 30 days; however, the nHAp/TiNT10% group showed statistically greater tissue repair, compared to the untreated control group. Thus, the results of this study demonstrate that the presently formulated nHAp/TiNT nanocomposites are promising for numerous improved bone tissue regeneration applications.

The production of nanoparticles for biomedical applications (namely with antimicrobial and anticancer properties) has been significantly hampered using traditional physicochemical approaches, which often produce nanostructures with poor biocompatibility properties requiring post-synthesis functionalization to implement features that such biomedical applications require. As an alternative, green nanotechnology and the synthesis of environmentally friendly nanomaterials have been gaining attention over the last few decades, using living organisms or biomolecules derived from them, as the main raw materials to produce cost-effective, environmentally friendly, and ready-to-be-used nanomaterials. In this article and building upon previous knowledge, we have designed and implemented the synthesis of selenium and tellurium nanoparticles using extracts from fresh jalapeño and habanero peppers. After characterization, in this study, the nanoparticles were tested for both their antimicrobial and anticancer features against isolates of antibiotic-resistant bacterial strains and skin cancer cell lines, respectively. The nanosystems produced nanoparticles via a fast, eco-friendly, and cost-effective method showing different antimicrobial profiles between elements. While selenium nanoparticles lacked an antimicrobial effect at the concentrations tested, those made of tellurium produced a significant antibacterial effect even at the lowest concentration tested. These effects were correlated when the nanoparticles were tested for their cytocompatibility and anticancer properties. While selenium nanoparticles were biocompatible and had a dose-dependent anticancer effect, tellurium-based nanoparticles lacked such biocompatibility while exerting a powerful anti-cancer effect. Further, this study demonstrated a suitable mechanism of action for killing bacteria and cancer cells involving reactive oxygen species (ROS) generation. In summary, this study introduces a new green nanomedicine synthesis approach to create novel selenium and tellurium nanoparticles with attractive properties for numerous biomedical applications.

The goal of this study is to synthesize, characterize and investigate some physicochemical properties of conductive polyaniline-g-polystyrene/Fe3O4 (Fe3O4/PSt-g-PANi) nanocomposites. For this purpose, initially, Fe3O4 nanoparticles were synthesized by a co-precipitation method. Then, the desired nanocomposite was synthesized in two steps. First, the atom transfer radical polymerization (ATRP) of styrene was performed using an ATRP initiator attached to the surface of Fe3O4 nanoparticles, followed by functionalization of the Fe3O4-PSt with amine groups (–NH2). Second, surface oxidative graft copolymerization of aniline was accomplished using the –NH2 moieties on the Fe3O4/PSt-NH2 as the anchoring sites. The prepared materials were characterized by various instruments, including TEM, SEM, TGA, EDX, FT-IR, XRD and conductivity measurements. The results indicated that the synthesized conductive polymer/Fe3O4 nanocomposites had higher electrical conductivity and thermal resistance than those of the corresponding homopolymers.

Aim The aim of the present study was to produce chrysin–curcumin-loaded PCL-PEG nanofibres by an electrospinning technique and to evaluate the biological activity of the chrysin–curcumin-loaded PCL-PEG fibres for wound healing and its related genes using in vivo methods.Materials and methods The electrospinning method was carried out for the preparation of the chrysin, curcumin and chrysin–curcumin-loaded PCL-PEG nanofibres with different concentrations. FTIR and SEM were performed to characterize the chemical structures and morphology of the nanofibres. In vitro drug release, as well as in vivo wound-healing studies were investigated in male rats. The expressions of genes related to the wound-healing process were also evaluated by real-time PCR.Results Our study showed that the chrysin–curcumin-loaded nanofibres have anti-inflammatory properties in several stages of the wound-healing process by affecting the IL-6, MMP-2, TIMP-1, TIMP-2 and iNOS gene expression. Our results demonstrated that the effect of the chrysin-loaded nanofibre, the curcumin-loaded nanofibre and the chrysin–curcumin-loaded nanofibre in the wound-healing process is dose dependent and in accordance with the obtained results in that it might affect the inflammation phase more than the other stages of the wound-healing process.Conclusion We have introduced chrysin–curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.

Three-dimensional bioprinting is a powerful technique for manufacturing improved engineered tissues. Three-dimensional bioprinted hydrogels have significantly advanced the medical field to repair cartilage tissue, allowing for such constructs to be loaded with different components, such as cells, nanoparticles, and/or drugs. Cartilage, as an avascular tissue, presents extreme difficulty in self-repair when it has been damaged. In this way, hydrogels with optimal chemical and physical properties have been researched to respond to external stimuli and release various bioactive agents to further promote a desired tissue response. For instance, methacryloyl gelatin (GelMA) is a type of modified hydrogel that allows for the encapsulation of cells, as well as oxygen-releasing nanoparticles that, in the presence of an aqueous medium and through controlled porosity and swelling, allow for internal and external environmental exchanges. This review explores the 3D bioprinting of hydrogels, with a particular focus on GelMA hydrogels, to repair cartilage tissue. Recent advances and future perspectives are described.

Porous nano-scaffolds provide for better opportunities to restore, maintain, and improve functions of damaged tissues and organs by facilitating tissue regeneration. Various nanohybrids composed of mesoporous silica nanoparticles (MSNs) are being widely explored for tissue engineering. Since biological activity is enhanced by several orders of magnitude in multicomponent scaffolds, remarkable progress has been observed in this field, which has aimed to develop the controlled synthesis of multifunctional MSNs with tuneable pore size, efficient delivering capacity of bioactive factors, as well as enhanced biocompatibility and biodegradability. In this review, we aim to provide a broad survey of the synthesis of multifunctional MSN based nanostructures with exotic shapes and sizes. Further, their promise as a novel nanomedicine is also elaborated with respect to their role in bone tissue engineering. Also, recent progress in surface modification and functionalization with various polymers like poly (l-lactic acid)/poly (ε-caprolactone), polylysine-modified polyethylenimine, poly (lactic-co-glycolic acid), and poly (citrate-siloxane) and biological polymers like alginate, chitosan, and gelatine are also covered. Several attempts for conjugating drugs like dexamethasone and β–estradiol, antibiotics like vancomycin and levofloxaci, and imaging agents like fluorescein isothiocyanate and gadolinium, on the surface modified MSNs are also covered. Finally, the scope of developing orthopaedic implants and potential trends in 3D bioprinting applications of MSNs are also discussed. Hence, MSNs based nanomaterials may serve as improved candidate biotemplates or scaffolds for numerous bone tissue engineering, drug delivery and imaging applications deserving our full attention now.

Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin–proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

Nanostructured silver (Ag) and gold (Au) are widely known to be potent biocidal and cytotoxic agents as well as biocompatible nanomaterials. It has been recently reported that combining both metals in a specific chemical composition causes a significant enhancement in their antibacterial activity against antibiotic-resistant bacterial strains, as well as in their anticancer effects, while preserving cytocompatibility properties. In this work, Ag/Au bimetallic nanoparticles over a complete atomic chemical composition range were prepared at 10 at% through a green, highly reproducible, and simple approach using starch as a unique reducing and capping agent. The noble metal nanosystems were thoroughly characterized by different analytical techniques, including UV-visible and FT-IR spectroscopies, XRD, TEM/EDS, XPS and ICP-MS. Moreover, absorption spectra simulations for representative colloidal Ag/Au-NP samples were conducted using FDTD modelling. The antibacterial properties of the bimetallic nanoparticles were determined against multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, showing a clear dose-dependent inhibition even at the lowest concentration tested (5 µg/mL). Cytocompatibility assays showed a medium range of toxicity at low and intermediate concentrations (5 and 10 µg/mL), while triggering an anticancer behavior, even at the lowest concentration tested, in a process involving reactive oxygen species production per the nanoparticle Au:Ag ratio. In this manner, this study provides promising evidence that the presently fabricated Ag/Au-NPs should be further studied for a wide range of antibacterial and anticancer applications.

Metallic nanoparticles, such as gold nanoparticles (AuNPs), have been extensively studied as drug delivery systems for various therapeutic applications. However, drug-loaded-AuNPs have been rarely explored in vivo for their effect on bacteria residing inside tissues. Ciprofloxacin (CIP) is a second-generation fluoroquinolone with a broad-spectrum of antibiotic properties devoid of developing bacteria resistance. This research is focused on the synthesis and physical characterization of Ciprofloxacin-loaded gold nanoparticles (CIP-AuNPs) and their effect on the colonization of Enterococcus faecalis in the liver and kidneys of mice. The successfully prepared CIP-AuNPs were stable and exerted enhanced in vitro antibacterial activity against E. faecalis compared with free CIP. The optimized CIP-AuNPs were administered (500 µg/Kg) once a day via tail vein to infected mice for eight days and were found to be effective in eradicating E. faecalis from the host tissues. Moreover, unlike CIP, CIP-AuNPs were non-hemolytic. In summary, this study demonstrated that CIP-AuNPs are promising and biocompatible alternative therapeutics for E.-faecalis-induced infections resistant to conventional drugs (e.g., beta-lactams and vancomycin) and should be further investigated.

Poly (lactic acid) (PLA) has been increasingly used in cutaneous tissue engineering due to its low cost, ease of handling, biodegradability, and biocompatibility, as well as its ability to form composites. However, these polymers possess a structure with nanoporous that mimic the cellular environment. In this study, nanocomposites are prepared using PLA and titanium dioxide (TiO2) (10 and 35%—w/w) nanoparticles that also function as an active anti-scarring agent. The nanocomposites were prepared using an electrospinning technique. Three different solutions were prepared as follows: PLA, 10% PLA/TiO2, and 35% PLA/TiO2 (w/w%). Electrospun PLA and PLA/TiO2 nanocomposites were characterized morphologically, structurally, and chemically using electron scanning microscopy, transmission electron microscopy, goniometry, and X-ray diffraction. L929 fibroblast cells were used for in vitro tests. The cytotoxic effect was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Versicam (VCAN), biglicam (BIG), interleukin-6 (IL6), interleukin-10 (IL-10), and type-1 collagen (COL1A1) genes were evaluated by RT-qPCR. In vivo tests using Wistar rats were conducted for up to 15 days. Nanofibrous fibers were obtained for all groups that did not contain residual solvents. No cytotoxic effects were observed for up to 168 h. The genes expressed showed the highest values of versican and collagen-1 (p < 0.05) for PLA/TiO2 nanocomposite scaffolds when compared to the control group (cells). Histological images showed that PLA at 10 and 35% w/w led to a discrete inflammatory infiltration and expression of many newly formed vessels, indicating increased metabolic activity of this tissue. To summarize, this study supported the potential of PLA/TiO2 nanocomposites ability to reduce cutaneous scarring in scaffolds.

Metallic materials are widely used for fabricating medical implants due to their high specific strength, biocompatibility, good corrosion properties, and fatigue resistance. Recently, titanium (Ti) and its alloys, as well as stainless steel (SS), have attracted attention from researchers because of their biocompatibility properties within the human body; however, improvements in mechanical properties while keeping other beneficial properties unchanged are still required. Severe plastic deformation (SPD) is a unique process for fabricating an ultra-fine-grained (UFG) metal with micrometer- to nanometer-level grain structures. SPD methods can substantially refine grain size and represent a promising strategy for improving biological functionality and mechanical properties. This present review paper provides an overview of different SPD techniques developed to create nano-/ultra-fine-grain-structured Ti and stainless steel for improved biomedical implant applications. Furthermore, studies will be covered that have used SPD techniques to improve bone cell proliferation and function while decreasing bacterial colonization when cultured on such nano-grained metals (without resorting to antibiotic use).