While most nanomedicines primarily aim to stimulate the immune system against infections or tumors, there is a growing demand for inducing immune tolerance under certain conditions, such as allergic and autoimmune diseases. Researchers have explored nanotechnology-based strategies to induce immune tolerance in a targeted and specific manner. One approach involves the use of nanoparticles (NPs) to encapsulate immunosuppressive drugs and/or antigens to educate naïve T cells and promote the generation of antigen-specific regulatory T cells that inhibit immune responses. However, this approach has certain limitations. The hydrophobicity of proteins or peptides restricts the degree to which they can be encapsulated in NPs, which in turn, affects their loading efficiency and treatment efficacy. With the emergence of mRNA lipid nanoparticle (LNP) platforms, there is the possibility of overcoming the limitations of protein and peptide encapsulation. To date, mRNA LNP systems have been shown to provide organ, cellular, and subcellular targeting for the induction of immune tolerance. This method of drug delivery is flexible and scalable that can be customized for a specific patient, resulting in an effective means of administering relevant proteins or epitopes to induce antigen-specific immune tolerance. With continued research and development, this technology could offer a safer and more effective alternative to current therapies, ultimately improving the quality of life of patients worldwide.
Two-dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly in the realms of immunotherapy for tissue engineering and tumor therapy. These applications necessitate a thorough assessment of the potential influence of 2D nanomaterials on immune cells. Notably, the mononuclear phagocyte system (MPS) cells, which play pivotal roles in both innate and adaptive immunity, are essential for maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to the prevention of foreign body invasion and the elimination of dead or senescent cells. Furthermore, MPS cells, including macrophages and dendritic cells, serve as vital bridges between innate and adaptive immune responses. Therefore, understanding the nano-bio interactions between 2D nanomaterials and MPS cells is imperative. These nano-bio interactions including cellular uptake, cytocompatibility, and immunological impact are invaluable for the purposeful design of 2D nanomaterials. Herein, we provide an overview of the latest advancements in understanding the nano-bio interactions between 2D nanomaterials and MPS cells, and discuss the current challenges and future prospects of employing 2D nanomaterials in the field of nanomedicine.
Although immunotherapy has revolutionized cancer therapy by providing efficient tumor growth suppression, long-term protection from recurrence as well as minimized side effects, the low response rate significantly limits the clinical application of immunotherapy in board types of solid tumors. In order to improve the therapeutic efficacy, conventional therapies including radiotherapy, chemotherapy, phototherapy and chemodynamic therapy are employed to combine with immunotherapy to elicit stronger antitumor immune responses. Polymer nanomedicines are frequently utilized in synergistic immunotherapy and other therapies owing to their tunable physiochemical properties, high drug loading capacity, ease of modification and low toxicity. With elaborate design and tailored properties, polymer nanomedicines can significantly enhance antitumor efficacy by enhancing tumor specificity, priming immune cells and amplifying immune responses in tumors. However, until now, there is no review solely dedicated to the comprehensive development of polymer-based platforms for combinational immunotherapy of cancers. Herein, this paper summarizes latest advances in the design, fabrication and application of polymer nanomedicines in combinational immunotherapy and traditional antitumor strategies including radiotherapy, chemotherapy, photothermal therapy, photodynamic therapy and other therapies. An outlook on the trajectory and potential challenges of polymer nanomedicines in bridging the gap between immunotherapy and conventional therapies is also discussed.
Hexagonal boron nitride (h-BN) nanomaterials are a rising star in the field of biomedicine. This review presents an overview of the progress in h-BN nanomaterials for biological applications. It begins with a general introduction of the structural characteristics of h-BN, followed by the brief introduction of its physical and chemical properties, including thermal, band and mechanical properties, chemical reactivity, biodegradability and biocompatibility, then emphasizes on the recent progress in the biomedical applications including drug delivery, boron neutron capture therapy (BNCT), bioimaging and nanozyme, and ends with the challenges and perspectives related to the biomedical applications. The advantages of BN nanomaterials used for biomedical applications were analyzed, and their problems were also discussed, inspiring the future rational designs of the BN nanomedicines.
Colorectal cancer is one of the most common cancers, and current treatment options include surgery, chemotherapy, and radiation therapy. Most patients undergo surgery, which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells, leading to postoperative pain and discomfort in daily routines. Although versatile therapeutic patches have been developed to induce tumor apoptosis, achieving both great adhesiveness on the mucus layers of the colon tissue and anti-cell/tissue adhesion to other surrounding organs remains a challenge. Herein, we report a Janus polysaccharide film comprising two polymers: mussel-inspired catechol-conjugated chitosan (Chi-C) with muco-adhesiveness, and alginate (Alg) with anti-adhesion property. The Chi-C and Alg polymers form a stably entangled bilayer film via electrostatic interactions. The Janus film shows a strong tissue adhesive strength of ˜10 kPa for the Chi-C layer and weak strength of ˜1 kPa for the Alg layer. Particularly, the Janus film encapsulating an anti-cancer drug exhibits a directional release profile to the tumor site, which is effective for triggering tumor death in in vivo colorectal tumor resection model. Ultimately, such anti-cancer material strategies using bilayered structures are promising for advanced tumor therapy.
Activating the stimulator of interferon genes (STING) signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment (TME). Herein, we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist (i.e., SR717) and a chemotherapeutic drug (i.e., curcumin). After intravenous administration, the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses. Meanwhile, the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1, leading to the reversal of the immunosuppressive TME. The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary, recurrent, and metastatic tumors. The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.
Osteoarthritis (OA) is a chronic and degenerative disease with limited clinical options for effective suppression. Recently, significant endeavors have been explored to reveal its pathogenesis and develop treatments against OA. Hydrogels, designed with a striking resemblance to the extracellular matrix, offer a biomimetic interaction with biological tissues, presenting a promising avenue for OA amelioration. As a result, biocompatible hydrogels have been erected incorporating on-demand bioactivities to optimize the intra-articular microenvironment, thereby alleviating OA symptoms and fostering the eventual regeneration of articular joints. This review highlights the collaborative objectives underlying the establishment of this tissue microenvironment, encompassing mechanical modulation, anti-inflammation, and tissue regeneration. Specifically, we consolidate recent advances in hydrogel-based biomaterials, serving as the tissue engineering scaffolds to replicate the lubrication properties of natural joints or the bioactive agent-loaded vehicles to combat localized inflammation. Additionally, hydrogels function as cell scaffolds to facilitate the maintenance of cellular homeostasis and contribute to the advancement of cartilage regeneration. Finally, this review outlines the prospective directions for hydrogel-mediated OA therapies.
In the quest for optimizing biodegradable implants, the exploration of piezoelectric materials stands at the forefront of biomedical engineering research. Traditional piezoelectric materials often suffer from limitations in biocompatibility and biodegradability, significantly impeding their in vivo study and further biomedical application. By leveraging molecular engineering and structural design, a recent innovative approach transcends the conventional piezoelectric limits of the molecules designed for biodegradable implants. The biodegradable molecular piezoelectric implants may open new avenues for their applications in bioenergy harvesting/sensing, implanted electronics, transient medical devices and tissue regeneration.