Advanced Nanobiomed Research最新文献

Basophils are the rarest circulating white blood cells (WBCs), but they play important roles in allergic disorders and other diseases. To enhance diagnostic capabilities, it would be desirable to isolate and analyze basophils efficiently from small blood samples. In 100 μL of whole blood, there are typically ≈10³ basophils, outnumbered by ≈10⁵ WBCs and ≈10⁸ red blood cells (RBCs). Basophils’ low abundance has therefore presented a significant challenge in their isolation from whole blood. Conventional in-bulk basophil isolation methods require lengthy processing steps and cannot work with small volumes of blood. Herein, a parallelized integrated basophil isolation device (pi-BID) is reported for the negative immunomagnetic selection of basophils directly from four samples of 100 μL of whole blood, in parallel, within 14 min including sample preparation time. The pi-BID interfaces directly with standard sample tubes, and uses a single pressure source to drive the flow in parallel microfluidic channels. Compared with conventional in-bulk basophil isolation, the pi-BID is >3× faster, and has higher purity (≈93%) and similar recovery (≈67%). Compared with other microfluidic devices for the immunomagnetic isolation of WBC subtypes, the pi-BID achieves 10× higher enrichment of target cells from whole blood, with no prior removal of RBCs necessary.

Metal–organic frameworks (MOFs), such as the magnetic resonance imaging-fit MIL-100 based on Fe, are gaining significant attention as versatile theranostics with high-loading capability. Moreover, as MOFs can be engineered to target tumors, there is much interest in applying them for precise pin-point treatment of cancer. Herein, Pd nanoparticles within MIL-100(Fe) are generated to create MOFs with remarkable photothermal conversion properties for cancer therapy. The Pd-loaded MIL-100(Fe) (Pd@MIL-100(Fe)) are stabilized with biocompatible block copolymers to generate MOFs with PEGylated surfaces. This is achieved by directly mixing poly(ethylene glycol)-poly(L-aspartic acid) (PEG-p(Asp)) or dopamine-modified PEG-p(Asp) (PEG-p(Asp-Dopa)) block copolymers with the MOFs in aqueous conditions. The resulting block copolymer-stabilized MOF hybrids are stable in physiological conditions. Particularly, the Pd@MIL-100(Fe)/PEG-p(Asp-Dopa) hybrids show enhanced blood circulation and increased accumulation in B16F10 melanoma. Furthermore, when irradiated with 808 nm light, the Pd@MIL-100(Fe)/PEG-p(Asp-Dopa) hybrids rapidly increase the temperature to 50 °C, enabling tumor remission. The surface-stabilized Pd@MIL-100(Fe)/polymer hybrids open viable opportunities for innovating MOF/polymer hybrid-based approaches for drug delivery.

Cells sense extracellular matrix-induced biophysical signals, which are transduced into intracellular signaling cascades, and trigger a series of cell responses, including adhesion, migration, and lineage commitment. Traditionally, in in vitro context, monofactorial approaches are employed to control cell fate, despite the fact that in vivo cells are exposed simultaneously to a diverse range of signals. Herein, an overview of key mechanotransduction pathways is first provided. Conventional single-factor and contemporary multifactorial methodologies, based on substrate rigidity and surface topography, are then reviewed to recapitulate in vitro the in vivo niche, in an attempt to elucidate the underlying mechanisms involved in human mesenchymal stromal cell-material interactions.

Liquid biopsy has received increasing attention as a new disease detection modality because of its noninvasive, simple sampling, and reproducible assay advantages. Among the markers of liquid biopsy, extracellular vesicles (EVs) are considered as promising disease biomarkers because they contain a large amount of biological information and have a significant role in physiological activities. The emergence and progression of some of these diseases are associated with miRNAs carried by EVs (EV-miRNAs). Therefore, high-sensitive detection of EV-miRNAs is essential in clinical applications. A growing number of strategies, including biosensors, in situ detection methods, and microfluidics have been developed for the detection of EV-miRNA and have been applied in the diagnosis of diseases such as cancer. This review summarizes the probes, signal amplification, and detection methods for EV-miRNA detection, as well as the application of membrane fusion-based in situ detection and integrated microfluidic chips for EV-miRNA detection. The challenges of these materials and techniques in clinical diagnostic applications are also discussed.

Traumatic brain injury (TBI) is one of the most common causes of disability and mortality worldwide, creating a large socioeconomic burden annually. Secondary injury physiopathology is known to play a prominent role in exacerbating neurodegeneration post-TBI and is potentially preventable by therapies. However, due to the heterogeneity of TBI and the complexity of the pathological mechanisms that ensue, there are currently no effective disease-modifying treatments to prevent TBI-associated disability and mortality. Nanotechnology has emerged in recent decades as a promising platform for the development of multifunctional neuroprotective agents for TBI. Herein, current multifunctional innovations are explored in this review in nanotechnology, which target the secondary injury pathological mechanisms of TBI and show promise in improving future post-TBI management. Also, potential new directions for the future development of TBI treatment are discussed.

2D materials exhibit a variety of characteristics that make them appealing platforms for cancer treatment such as high drug loading capacity and photothermal and photodynamic properties. A key advantage of 2D material platforms for oncological applications is the ability to harness multiple modalities including drug delivery, photothermal therapy, photodynamic therapy, chemodynamic therapy, gene delivery, and immunotherapy approaches for improved efficacy. In this review, a comparison of the unique properties of different classes of 2D materials that enable their usage as platforms for multimodal therapy is provided. Further, the benefits and drawbacks of different platforms are also highlighted. Finally, current challenges and emerging opportunities for future development of 2D materials to further enable combination therapy and translation from the bench to clinical oncology applications are discussed.

The therapeutic modes of cancers have been profoundly renovated by immunotherapies, which have shown extraordinary treating efficacy in certain tumor entities. However, the majority of cancer patients have not profited from it because of the negative effects of tumor microenvironment (TME) on human innate and/or adaptive immunity, including hypoxia, acidification, irregular vasculature, and a plethora of immunosuppressive cells and small molecules, which contribute to tumor progression, migration, resistance to drug, and so forth. Accordingly, it is feasible to enhance the efficacy of immunotherapies and increase the patients’ survival through the restructure of TME. Herein, the mechanisms and reverberations of aforementioned immunosuppressive elements are concentrated on, and latest therapeutic achievements and combined technologies that have been demonstrated effective in boosting immunotherapies by TME modulation are enumerated.

Nonspecific immunotherapies often induce general immune activation or suppression. Conversely, antigen-specific immunotherapy, which refers to dampening or augmenting adaptive immunity against a disease-specific antigen, increases T-cell target specificity to pathological tissues, thereby reducing side effects on the rest of the immune system. Advances in engineering strategies for nanomaterials have enabled the feasible modulation of their physicochemical features to incorporate antigens and inherently interact with innate immune cells, which remarkably amplifies the orchestration of antigen-specific immune responses against cancer and autoimmune diseases. From this contemporary perspective, the basic principles of antigen-specific immunotherapy are briefly introduced and we elucidate how the latest nanoengineering paradigms regulate the functions of heterogeneous subsets of immune cells, such as antigen-presenting cells, B cells, and regulatory or cytotoxic T cells, promoting antigen-specific immunotherapy to treat autoimmune diseases and cancer. An outlook on prospects and remaining challenges have been discussed for, translating scientific discoveries of powerful nanomaterials into medical advances in antigen-specific immunotherapy, thus offering new treatment modalities for patients with unmet needs.

Complete resection without damaging the capsule is the gold-standard surgical approach for nonmetastatic gastrointestinal stromal tumors (GIST). However, accurately locating tumors during surgery is challenging because GIST is covered by normal mucosal tissue, leading to suboptimal surgeries and increased cancer recurrence rates. To enhance surgical care for GIST, a cutting-edge near-infrared (NIR) fluorescent nanoprobe is presented that enables real-time navigation of GIST by specifically targeting CD117, a protein frequently overexpressed in GIST. By attaching a zwitterionic NIR fluorophore called ZW800-1C to a CD117 ligand, stem cell factor (SCF), precise targeting is achieved while minimizing nonspecific tissue interactions. In in vitro studies, the high affinity of nanoprobe for CD117-positive GIST-T1 cell lines is demonstrated, while exhibiting no binding to CD117-negative cells or GIST-5 R cells. In a xenograft model of GIST-T1 in mice, the nanoprobe produces strong and persistent NIR signals that last over 72 h following a single intravenous injection. Moreover, the nanoprobe successfully detects spontaneous tumors in the cecum of heterozygous Kit K641E mice. In these findings, the promise of CD117-targeted molecular imaging is highlighted as an intraoperative strategy for GIST. Furthermore, this imaging approach holds potential for early diagnosis, as well as monitoring GIST prognosis before and after surgical resection.

ε-poly-l-lysine (ε-PLL) is a natural polypeptide/polycation originating from bacteria. Thanks to its antifungal and antibacterial properties, it is the subject of extensive research in the food and medical industries. ε-PLL is also used to develop biomaterials in a broad range of applications, such as drug delivery, wound healing, or antimicrobial coatings. Indeed, loading ε-PLL inside nanoparticles, functionalizing implant surfaces with ε-PLL, or developing hydrogels based on reactions between ε-PLL and other polymers can improve the materials properties, leading to biocompatible, antibacterial, and antifungal systems. These characteristics are necessary not only for the development of biomaterials, for their integrity in a biological environment, but also for improving the performances of medical devices. Moreover, ε-PLL can be used as an alternative to antibiotics as its mechanism of action reduces the bacterial resistance risk compared with antibiotics. Finally, “smart” systems using ε-PLL may be developed, with controllable material degradation or drug delivery via pH or temperature variations. This review sought to gather the latest research on the development of antimicrobial biomaterials based on the ε-PLL polypeptide.