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Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to pose a significant threat to global health. The resilience of TB is amplified by a myriad of physical, biological, and biopharmaceutical barriers that challenge conventional therapeutic approaches. This review navigates the intricate landscape of TB treatment, from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression. Amidst these challenges, traditional therapies often fail, contending with inconsistent bioavailability, prolonged treatment regimens, and socioeconomic burdens. Nanoscale Drug Delivery Systems (NDDSs) emerge as a promising beacon, ready to overcome these barriers, offering better drug targeting and improved patient adherence. Through a critical approach, we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo. This review advocates for the intensification of research in NDDSs, heralding their potential to reshape the contours of global TB treatment strategies.

Abstract Efficient intracellular delivery is crucial for biotherapeutics, such as proteins, oligonucleotides, and CRISPR/Cas9 gene-editing systems, to achieve their efficacy. Despite the great efforts of developing new intracellular delivery carriers, the lack of straightforward methods for intracellular delivery quantification limits further development in this area. Herein, we designed a simple and versatile bioorthogonal luminescent reaction (BioLure assay) to analyze intracellular delivery. Our results suggest that BioLure can be used to estimate the amount of intracellularly delivered molecules after electroporation, and the estimation by BioLure is in good correlation with the results from complementary methods. Furthermore, we used BioLure assay to correlate the intracellularly-delivered RNase A amount with its tumoricidal activity. Overall, BioLure is a versatile tool for understanding the intracellular delivery process on live cells, and establishing the link between the cytosolic concentration of intracellularly-delivered biotherapeutics and their therapeutic efficacy.

Abstract Ionotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.

Abstract Lycopene (LYC), a carotenoid extracted mainly from tomatoes, has several biological properties, making its use desirable as a nutraceutical and pharmaceutical active ingredient. Among its various applications vulvovaginal candidiasis stands out. However, the use of LYC in therapy has limitations related to its solubility and stability. In this study, mesoporous silica nanoparticles (MSNs) are used to load and protect LYC from degradation. The exact amount of drug incorporated was determined by analytical techniques, such as high‐performance liquid chromatography (HPLC) and thermal analysis. For this, we developed and validated an HPLC method for LYC quantification and evaluated LYC impregnation in MSNs, followed by thermogravimetry analysis (TGA). Differential scanning calorimetry (DSC) was also used in order to confirm drug incorporation. Additionally, an in vitro release study in simulated vaginal fluid was also carried out. The HPLC method was duly validated for the range of 26–125 µg mL−1 and proved to be suitable for LYC quantification. DSC measurements suggest an improvement in the stability of the impregnated drug, which was reinforced by the release assay. Overall, the developed method is suitable to quantify LYC‐loaded porous materials enabling its use in vaginal applications.

ABSTRACT This Special Issue is dedicated to current research activities on Advanced Porous Materials within the framework of “The NETPORE COST Action,” providing a collection of 12 outstanding contributions (four review papers and eight original research papers) from diverse research groups on the latest progresses regarding porous nano‐ and micro‐materials for diverse applications. The contributions herein address the impact of porous materials in basic science, batteries, biosensing, and translational and personalized medicine for the treatment of various diseases. Overall, this Special Issue is expected to provide important background and new knowledge on the latest advances in porous materials and their broad applications.

Abstract Infectious diseases are a global public health concern generated by uncontrolled uses of antimicrobials resulting in multidrug‐resistant (MDR) pathogens. The antimicrobial resistance (AMR) has made explicit the ineffective action of the current medicines and vaccines. Rapid diagnosis and effective treatment are the keys to reduce the capacity of MDR pathogens spreading very fast, avoiding high socioeconomic impact, severe and prolonged illness and death. Advanced porous materials have emerged as promising alternatives to the conventional diagnoses and therapy due to their low‐cost production, high biocompatibility, adjustable porous structure, large surface area, easy surface functionalization and capacity of loading high drugs amount. In this review, we first highlighted the current strategies to fight against infectious diseases. Then, we introduce the main advanced porous materials used in infectious diseases, including mesoporous silica nanoparticles (MSNs), porous silicon nanoparticles (PSiNPs), metal–organic frameworks (MOFs), covalent–organic frameworks (COFs), hydrogen‐bonded organic frameworks (HOFs) and porous carbon materials. The strategies to fabricate these materials and their characterization for the application in the recent years for antimicrobial treatment is also discussed. Finally, we present an overview outlook and challenges on the future application of such materials for infectious diseases.

Bone tissue engineering (BTE) involves the design of three-dimensional (3D) scaffolds that aim to address current challenges of bone defect healing, such as limited donor availability, disease transmission risks, and the necessity for multiple invasive surgeries. Scaffolds can mimic natural bone structure to accelerate the mechanisms involved in the healing process. Herein, a crosslinked combination of biopolymers, including gelatin (GEL), chitosan (CS), and hyaluronic acid (HA), loaded with diatom (Di) and β-sitosterol (BS), is used to produce GCH-Di-S scaffold by freeze-drying method. The GCH scaffold possesses a uniform structure, is biodegradable and biocompatible, and exhibits high porosity and interconnected pores, all required for effective bone repair. The incorporation of Di within the scaffold contributes to the adjustment of porosity and degradation, as well as effectively enhancing the mechanical property and biomineralization. In vivo studies have confirmed the safety of the scaffold and its potential to stimulate the creation of new bone tissue. This is achieved by providing an osteoconductive platform for cell attachment, prompting calcification, and augmenting the proliferation of osteoblasts, which further contributes to angiogenesis and anti-inflammatory effects of BS.

In the last years there has been a booming in the development of biological pharmaceuticals, and various nanoparticle delivery systems have been developed to overcome biological barriers to maximize the therapeutic potentials. Especially, when these drug-loaded nanoparticle systems arrive at the target cells, they must be successfully internalized into the cells, followed by the endosome escape, to release the payload in the cytoplasm. This is crucial so that the payloads are not degraded in the endosome (around pH 6.8–6.0) or lysosome (around pH 4.5). Considering the acid environment of the endosome, several studies have shown the design of different acid-labile nanoparticle delivery systems attempting to achieve endosome escape by, for example, endosomal rupture, membrane destabilization, and membrane fusion. In this mini-review, we summarize current designs in acid-labile chemical bonds for endosome escape of nanosystems. First, we briefly introduce the structural design of acid-labile nanoparticles and their endosomal escape mechanisms. Then, we review recent research work on the topic, highlighting how the nanoparticle designs can be used in endosome escape for different biomedical applications. Finally, we discuss the challenges and future perspectives in this field.

Fenton and Fenton like reaction have been well clarified as efficient reactive oxygen species (ROS) sources in tumor, and have been widely developed into a cancer treatment method. Meanwhile, transition metal-based nanomaterials with Fenton or Fenton like reaction characteristics also have been well explored as therapeutic agents for the cancer therapy, mainly in chemo-dynamic and ferroptosis induced cancer therapy. Herein,to summarize recent advances in Fenton and Fenton like reaction mediated nanoparticles for cancer therapy, in this minireview, we first introduced the mechanisms of Fenton and Fenton like reaction and two therapeutic methods based on Fenton and Fenton like reaction, and then we introduced the well-designed nanoparticles with Fenton reaction or Fenton-like reaction characteristics for the cancer therapies. Finally its challenges and perspectives are discussed.

Micro-nano hydrogel is a novel functional material that has attracted extensive attention in various fields. Due to the size of micron and nano level, high water content and high specific surface area, the micro-nano hydrogels can achieve minimally invasive repair and are considered as promising agents in tissue repair engineering. In this review, we summarize the design and development of micro-nano hydrogels for biomedical applications, first introduce biopolymers for the synthesis of hydrogels, then introduce the preparation technologies of microgels and nanogels respectively, and systematically summarize the application characteristics and forms of different preparation technologies. Finally, the latest application progresses of microgels in local drug delivery, bone tissue repair, soft tissue repair and immunomodulation are introduced in detail, as well as the latest application progress of nanohydrogels in cartilage repair, antibacterial, antitumor/cancer nerve repair and prevention and diagnosis of diseases, and the key research directions of micro-nano hydrogel preparation technologies in the future are clarified.

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.

Abstract Macrophage targeting and researches centered on immunological responses have received interest thanks to studies unveiling the significant role of macrophages in inflammatory diseases and cancer. In this regard, we have selected four types of nanoparticles (NPs), including acetalated dextran‐based nano‐carrier functionalized with atrial natriuretic peptide and linTT1(AcDEX‐PEG‐TT1‐ANP), PEGylated acetalated dextran (AcDEX‐PEG), acetalated dextran (AcDEX), and hyaluronic acid (HA) to investigate their interactions with macrophage membrane. Using microsecond coarse‐grained molecular dynamics (MD) simulations, we studied the interactions between the NPs and the macrophage membrane and subsequent immunological reactions that occur after the penetration of the NPs within the macrophage cell. Different parameters that determine the strength and amount of macrophage membrane interaction were measured and compared for all four types of NPs. The results showed that AcDEX‐PEG‐TT1‐ANP has the most favorable interaction with the macrophage membrane while HA has the least favorable results by comparison. Moreover, drug encapsulation and release in different pH conditions showed the pH‐responsivity of the considered NPs for drug delivery in acidic environments. On the other hand, evaluations with human serum albumin (HSA), fibrinogen (Fib), and transferrin (Tf) declared that peptide modified AcDEX polymers are the most probable NPs to absorb a layer of the protein corona.

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.

Intravenously administered nanocarriers suffer from off-target distribution, pre-targeting drug leakage, and rapid clearance, limiting their efficiency in tumor eradication. To bypass these challenges, an injectable hydrogel with time- and temperature-dependent viscosity enhancement behavior and self-healing property are reported to assist in the retention of the hydrogel in the tumor site after injection. The cancer cell membrane (CCM) and sorafenib are embedded into the hydrogel to elicit local tumor-specific immune responses and induce cancer cell apoptosis, respectively. In addition, hyaluronic acid (HA) coated Bi2S3 nanorods (BiH) are incorporated within the hydrogel to afford prolonged multi-cycle local photothermal therapy (PTT) due to the reduced diffusion of the nanorods to the surrounding tissues as a result of HA affinity toward cancer cells. The results show the promotion of immunostimulatory responses by both CCM and PTT through the release of inflammatory cytokines from immune cells, which allows localized and complete ablation of the breast tumor in an animal model by a single injection of the hydrogel. Moreover, the BiH renders strong antibacterial activity to the hydrogel, which is crucial for the clinical translation of injectable hydrogels as it minimizes the risk of infection in the post-cancer lesion formed by PTT-mediated cancer therapy.

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (Papp) of 2.37 × 10−6 cm/s, over the 1.66 × 10−6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model.

Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing. How to programmatically activate sequential immune responses is the key for scarless skin regeneration. In this study, an “Inner-Outer” IL-10-loaded electrospun fiber with cascade release behavior was constructed. During the inflammatory phase, the electrospun fiber released a lower concentration of IL-10 within the wound, inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype “M2c” to suppress excessive inflammation response. During the proliferative phase, a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized “M2c” directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration. The “Inner-Outer” IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration, which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.

Abstract Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast‐targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic‐co‐glycolic) acid cores, these nanoparticles, termed fibroblast membrane‐camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor‐β, interleukin (IL)‐11, IL‐13, and IL‐17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof‐of‐concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad‐spectrum therapy for fibrosis management.

Artificial intelligence (AI) methods are explosively considered in the design and optimization of drug discovery and delivery systems. Herein, machine learning methods are used for optimizing the production of curcumin (CUR)‐loaded nanofibers. The required data are mined through the literature survey and two categories, including material‐ and machine‐based parameters, are detected and studied as effective parameters on the final outcomes. AI results show that high‐density polymers have a lower CUR release rate; however, with the increase in polymer density, CUR encapsulation efficiency (EE) increases in many types of polymers. The smallest diameter, highest EE, and highest drug release percentage are obtained at a molecular weight between 100 and 150 kDa and a CUR concentration of 10–15 wt%, with the polymer density in the range of 1.2–1.5 g mL−1. Also, the optimal distance of ≈23 cm, the flow rate of 3.5–4.5 mL h−1, and the voltage at the range of 12.5–15 kV result in the highest release rate, highest EE, and the lowest average diameter for fibers. These findings open up new roads for future design and production of drug‐loaded polymeric nanofibers with desirable properties and performances by AI methods.

Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices, leading to significant mortality in clinic. To address this issue, here, we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide, with bio-orthogonal click chemistry, to tailor the surface functionalities of tubing and catheters. Inspired by mussel adhesive foot protein, a bioclickable peptide mimic (DOPA)4-azide-based structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry. Then, the dibenzylcyclooctyne (DBCO) modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions and the DBCO-modified antimicrobial peptide (DBCO-AMP) are clicked onto the grafted surfaces via bio-orthogonal reaction. The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous s-nitrosothiols to resist adhesion/activation of platelets, thus preventing the formation of thrombosis. Overall, this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.

Abstract Diabetes mellitus (DM) refers to a group of metabolic disorders that are characterized by hyperglycemia. Oral subcutaneously administered antidiabetic drugs such as insulin, glipalamide, and metformin can temporarily balance blood sugar levels, however, long‐term administration of these therapies is associated with undesirable side effects on the kidney and liver. In addition, due to overproduction of reactive oxygen species and hyperglycemia‐induced macrovascular system damage, diabetics have an increased risk of complications. Fortunately, recent advances in nanomaterials have provided new opportunities for diabetes therapy and diagnosis. This review provides a panoramic overview of the current nanomaterials for the detection of diabetic biomarkers and diabetes treatment. Apart from diabetic sensing mechanisms and antidiabetic activities, the applications of these bioengineered nanoparticles for preventing several diabetic complications are elucidated. This review provides an overall perspective in this field, including current challenges and future trends, which may be helpful in informing the development of novel nanomaterials with new functions and properties for diabetes diagnosis and therapy.

Cancer therapy using oncolytic virus has shown pre-clinical and clinical efficacy. Here, the authors report ExtraCRAd, an oncolytic virus cloaked with tumour cell membrane and report its therapeutic effects in vitro and in vivo in multiple mouse tumour models.

Abstract The small interfering RNA (siRNA)‐based therapeutics have raised great attention since the first RNA interference (RNAi)‐derived drug, patisiran, was approved by the US Food and Drug Administration, which represented a landmark in the field of gene therapy. Given the properties of interfering disease‐associated gene expression, RNAi machinery is regarded as an essential factor for preparing precise medicine. However, over the past few years, siRNA drugs are undergoing a period of clinical translation, in which the major hurdle is the limited efficient delivery strategies. Therefore, this mini‐review mainly focuses on describing the state‐of‐the‐art of the nanoscale platforms for delivering siRNA payloads, also addressing their applications in cancer therapy. Finally, the status of siRNA drugs under clinical trials is discussed, providing a comprehensive understanding on the field of oligonucleotide‐mediated therapeutics.

Abstract Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL‐1β mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA‐grafted HA (DNAHA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio‐stability of the system. After loading SNAs, the constructed DNAHA‐SNAs system (HA‐SNAs) performs a reversible NIR‐triggered on‐demand release of SNAs by photo‐thermal induced DNA dehybridization and followed by post‐NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down‐regulated catabolic proteases and up‐regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.

Abstract Over the past decades, considerable attention has been dedicated to the exploitation of diverse immune cells as therapeutic and/or diagnostic cell‐based microrobots for hard‐to‐treat disorders. To date, a plethora of therapeutics based on alive immune cells, surface‐engineered immune cells, immunocytes’ cell membranes, leukocyte‐derived extracellular vesicles or exosomes, and artificial immune cells have been investigated and a few have been introduced into the market. These systems take advantage of the unique characteristics and functions of immune cells, including their presence in circulating blood and various tissues, complex crosstalk properties, high affinity to different self and foreign markers, unique potential of their on‐demand navigation and activity, production of a variety of chemokines/cytokines, as well as being cytotoxic in particular conditions. Here, the latest progress in the development of engineered therapeutics and diagnostics inspired by immune cells to ameliorate cancer, inflammatory conditions, autoimmune diseases, neurodegenerative disorders, cardiovascular complications, and infectious diseases is reviewed, and finally, the perspective for their clinical application is delineated.

The generation of biomimetic nanoparticles that retain the integrity of proteins has been a challenge. Here, the authors generate biomimetic nanoparticles that are exocytosed from tumour cells and show their therapeutic potential in targeting tumours and cancer stem cells in multiple mouse models.

Abstract Surgical resection is commonly used for therapeutic management of different solid tumors and is regarded as a primary standard of care procedure, but precise localization of tumor margins is a major intraoperative challenge. Herein, a generalized method by optimizing gold nanoparticles for intraoperative detection and photothermal ablation of tumor margins is introduced. These nanoparticles are detectable by highly sensitive surface‐enhanced Raman scattering imaging. This non‐invasive technique assists in delineating the two surgically challenged tumors in live mice with orthotopic colon or ovarian tumors. Any remaining residual tumors are also ablated by using post‐surgical adjuvant photothermaltherapy (aPTT), which results in microscale heat generation due to interaction of these nanoparticles with near‐infrared laser. Ablation of these post‐operative residual micro‐tumors prolongs the survival of mice significantly and delays tumor recurrence by 15 days. To validate clinical translatability of this method, the pharmacokinetics, biodistribution, Raman contrast, aPTT efficiency, and toxicity of these nanoparticles are also investigated. The nanoparticles have long blood circulation time (≈24 h), high tumor accumulation (4.87 ± 1.73%ID g−1) and no toxicity. This high‐resolution and sensitive intraoperative approach is versatile and can be potentially used for targeted ablation of residual tumor after resection within different organs.

The natural healing capacity of the tendon tissue is limited due to the hypovascular and cellular nature of this tissue. So far, several conventional approaches have been tested for tendon repair to accelerate the healing process, but all these approaches have their own advantages and limitations. Regenerative medicine and tissue engineering are interdisciplinary fields that aspire to develop novel medical devices, innovative bioscaffold, and nanomedicine, by combining different cell sources, biodegradable materials, immune modulators, and nanoparticles for tendon tissue repair. Different studies supported the idea that bioscaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potentiality. However, available data are lacking to allow definitive conclusion on the use of bioscaffolds for tendon regeneration and repairing. In this review, we provide an overview of the current basic understanding and material science in the field of bioscaffolds, nanomedicine, and tissue engineering for tendon repair.

Abstract The analysis of nanoparticles’ biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio–nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro‐inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor κB pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease‐specific or personalized manner.

Abstract The development of science and technology often drew lessons from natural phenomena. Herein, inspired by drying‐driven curling of apple peels, hydrogel‐based micro‐scaled hollow tubules (MHTs) are proposed for biomimicking microvessels, which promote microcirculation and improve the survival of random skin flaps. MHTs with various pipeline structures are fabricated using hydrogel in corresponding shapes, such as Y‐branches, anastomosis rings, and triangle loops. Adjustable diameters can be achieved by altering the concentration and cross‐linking time of the hydrogel. Based on this rationale, biomimetic microvessels with diameters of 50–500 µm are cultivated in vitro by coculture of MHTs and human umbilical vein endothelial cells. In vivo studies show their excellent performance to promote microcirculation and improve the survival of random skin flaps. In conclusion, the present work proposes and validifies a biomimetic 3D self‐forming method for the fabrication of biomimetic vessels and microvascular scaffolds with high biocompatibility and stability based on hydrogel materials, such as gelatin and hyaluronic acid.

Abstract Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration.

Electrospinning was used as a novel technique for fabricating polymeric nanofibers of a serum cholesterol lowering and poorly water-soluble plant sterol, β-sitosterol. Chitosan was used as a stabilizer/carrier polymer. The mean diameters of nanofibers ranged from 150 nm to 218 nm. β-sitosterol was in an amorphous form and homogeneously dispersed in the nanofibers. The β-sitosterol-loaded nanofibers were freely water-soluble and exhibited very short lag-time in releasing the plant sterol. The dissolution was associated with an immediate recrystallization of β-sitosterol in submicron level. In conclusion, electrospinning is a promising future technology for the formulation of poorly water-soluble plant sterols.

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.