Advanced Nanobiomed Research最新文献

Nanomedicine-induced cancer cell death has become a prominent area of research in the life sciences field in recent years. The concept of cuproptosis was first proposed in 2022. Copper homeostasis in organisms is tightly regulated by protein transporters and molecular chaperones. Disruptions in copper homeostasis can adversely affect mitochondrial respiration and disrupt other physiological processes, leading to cytotoxicity. Therefore, researchers have designed and refined copper-based nanomaterials to induce cuproptosis and assess their effects on cancer treatment. While several reviews on cuproptosis exist, they primarily delve into its molecular mechanisms. This review begins with elucidating the metabolism and homeostasis of copper in the body. Subsequently, the latest advancements in copper nanomaterial-induced cuproptosis for cancer treatment and antimicrobial purposes is summarized. Finally, a comprehensive summary and outlook on the subject is provided. The goal with this review is to assist researchers in gaining a deeper understanding of the interaction between nanomaterials and cuproptosis, thereby offering new perspectives for designing novel nanomaterials to induce cuproptosis.

In recent years, highly specialized nanoscopic drug carriers have been developed, which can, e.g., traverse biological barriers, protect drugs against harsh physiological conditions, and release such drugs in a controlled manner. However, for the delivery of particles via the respiratory pathway, aerodynamic diameters in the range of several micrometers are required to achieve good lung deposition and biodistribution. To combine the favorable properties of inhalable, micron-sized particles with the advantages of nanosized drug carriers, herein, dry-powder, hybrid microparticles (h-μPs), which disintegrate upon contact with moist surfaces (as present in the lung) to release the embedded nanoparticles into the mucosa, are introduced. Furthermore, a microfluidic setup, which mimics the air–gel interface of the mucosal airway epithelium, is presented. With this setup, the interaction of airborne h-μPs with the mucosal interface on a microscopic level is investigated. In detail, the influence of the h-μP charge on their deposition efficiency is tested and it is found that this process is governed by a combination of electrostatic interactions between the mucosal surface and the h-μPs as well as hygroscopic effects. Thus, this approach can help to optimize inhalable drug carriers to increase the efficiency of pulmonary drug administration via the respiratory pathway.

Cancer Treatment

Oral cancer shows an acidic tumor microenvironment. A pH-sensitive tertiary amine monomer dodecylmethylaminoethyl methacrylate (DMAEM) has been designed, which displays reversible protonation and deprotonation reactions according to the pH changes. In the acidic microenvironment DMAEM could be protonated into strong cytotoxic quaternary ammonium monomers - Dimethylaminododecyl methacrylate (DMADDM). By this means, DMAEM inhibits the progression of oral cancer. More details can be found in article number 2300119 by Bolei Li, Lei Cheng, and co-workers.

Photoactivatable carbon monoxide-releasing molecules (CORMs), typically based on transition-metal carbonyl complexes, have reliance on activation by UV or visible light that restricts their biomedical applications. To address this limitation, a near-infrared (NIR)-responsive nanoplatform is presented based on upconversion nanoparticles (UCNPs) loading with manganese carbonyl complex Mn₂(CO)₁₀ that concurrently releases CO and manganese ion (Mn²⁺). With the UCNPs, the more tissue-penetrable NIR is used to locally generate UV light for photodecomposition of Mn₂(CO)₁₀ into CO and manganese oxide (MnO_X), after which MnO_X is reduced to Mn²⁺ by the overexpressed glutathione in cancer cells. Moreover, the released Mn²⁺ can serve as a magnetic resonance imaging contrast agent to monitor the NIR-controlled corelease of CO and Mn²⁺ in real time. Therefore, this nanoplatform can provide a potential strategy for NIR-enabled spatiotemporally release of CO and Mn²⁺, enhancing the controlled delivery and biomedical application of CORMs.

This study aims to evaluate the therapeutic potential of cationic liposomal neostigmine bromide (NB), a novel drug delivery system, for the treatment of detrusor underactivity. By comparing the characteristics of NB-liposomes (NLP), NB-β-cyclodextrin inclusion complex liposomes (NCLP), and NB-mesoporous silica nanoparticle@CaCO₃ liposomes (NMCLP), NMCLP is selected as the main research subject. It has an average particle size and zeta potential of 100 nm and +50 mV, and its encapsulation efficiency and loading capacity of NB are 14.75% and 12.8%, respectively. Most importantly, NMCLP shows the best in vitro release performance among the three liposomes, demonstrating its ability in sustained release of NB. During cell and animal assays, efficient cellular uptake of liposomes through liposome-specific pathways is observed, facilitating targeted drug delivery, and in vivo experiments demonstrate the efficacy of NMCLP in improving bladder function in mice. Urodynamic measurements show increased bladder capacity and reduced voiding pressure, indicating enhanced bladder muscle activity. Histological analysis reveals the distribution and deep penetration of NMCLP within bladder tissues, supporting its localized drug effect. Therefore, NMCLP holds promise as a targeted and effective therapeutic strategy for detrusor underactivity.

Back pain is a global epidemiological and socioeconomic problem affecting up to 80% of people at some stage during their life and is often due to degeneration of the intervertebral disc (IVD). Therapies aimed at restoring the intradiscal space have predominantly focused on delivery of biomaterials, cells, or growth factors, among others, with variable degrees of success. While viral gene delivery strategies have emerged as promising therapeutic options in recent years, these approaches often have off-target effects and are associated with immunogenicity risks and other comorbidities. Consequently, nonviral methods have gained traction as potential avenues for gene delivery. Herein, enhanced cell-penetrating peptide (CPP) systems are used to deliver microRNAs in an in vitro and ex vivo model of disc degeneration. The data suggest that nanoparticle complexation of CPPs with (miR-221-inhibitor + miR-149-mimic) promotes protective effects in nucleus pulposus cells challenged with inflammatory cytokines TNF-α and IL-1β. Specifically, increases in matrix deposition, significant decreases in the secretion of an array of inflammatory cytokines, and decreased expression of matrix degradation enzymes MMP13 and ADAMTS5 are observed. These miR-CPP nanocomplexes can be further employed for targeting of the pericellular matrix space through homing, thus providing a promising approach for therapies of the intradiscal space.

Hydrogels have emerged as a focal point of research in the biomedical field due to their applications in tissue repair. However, the majority of hydrogels lack the capability to release oxygen, constraining their therapeutic outcomes in environments with hypoxic tissues. In recent years, oxygen-releasing hydrogels have garnered extensive attention in the field of tissue engineering, owing to their ability to modulate oxygen release and meet the diverse oxygenation requirements of various tissues. These hydrogels can enhance repair efficiency and promote tissue regeneration in hypoxic tissue environments. The design of oxygen-releasing hydrogels primarily involves the utilization of diverse oxygen sources, such as algae, perfluorocarbons, and peroxides, to achieve optimal tissue oxygenation. This review provides a comprehensive summary of the design and fabrication strategies of oxygen-releasing hydrogels, discusses deeply into their underlying oxygen-releasing mechanisms, and their myriad applications in tissue repair along with the prospective challenges.

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first-line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off-target toxicity caused by the whole-body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti-HBV therapeutics and discusses the opportunities and challenges for the future development of anti-HBV nanotherapeutics.

Chemotherapy-induced peripheral neuropathy (CIPN) poses challenges like pain and numbness, necessitating innovative treatments due to current limitations. Conventional approaches, relying on pain relief medications and dose adjustments, fall short in addressing neurotoxicity, resulting in inadequate pain relief and undesired effects. Aconite root (AR), a medicinal herb withcenturies of use against various diseases, contains a compound named Aconine, which alleviates pain by blocking specific neural channels. However, AR also contains Aconitine, a toxic substance hydrolyzed into nontoxic Aconine through heating. Herein, hyaluronate-poly(lactic-co-glycolic acid) nanoparticles (HA-PLGA/AR NPs) encapsulating Aconine are fabricated, enabling controlled release, protection, and transdermal delivery, enhancing therapeutic outcomes. High-performance liquid chromatography identifies optimal Aconine content after 48 h of AR boiling, with minimal neural toxicity confirmed. Characterization via transmission electron microscopy, dynamic light scattering, and in vitro assays demonstrates superior drug release by HA-PLGA/AR NPs, establishing effective transdermal Aconine delivery. In an in vitro CIPN model with paclitaxel (PTX)-treated PC12 cells, HA-PLGA/AR NPs stimulate enhanced neurite growth, validating their localized analgesic impact on CIPN and suggesting potential symptom alleviation. Taken together, HA-PLGA/AR NPs offer a promising strategy for controlled transdermal Aconine delivery, potentially alleviating CIPN and addressing various neuropathies and diseases.

Hypoxia in malignant tumors is a major factor in inducing the failure of clinical cancer treatment. Although several strategies have been developed to relieve hypoxia, most are still in the preclinical research phase. Therefore, hyperbaric oxygen (HBO), an approved adjuvant therapy for alleviating hypoxia clinically, is an excellent choice for enhancing the efficacy of cancer treatment that is impeded by tumor hypoxia. In this minireview, recent advances in HBO-facilitated cancer treatment, including clinical applications and nanomedicine-mediated cancer therapy are introduced. At the end of this minireview, the potential challenges faced by HBO therapy before clinical use are discussed. It is hoped that this review will provide a reference for future clinical research on the application of HBO in cancer treatment.