Journal of Nanobiotechnology最新文献

Nanocarrier drug delivery systems (NDDS) have gained momentum in the field of anticancer or nucleic acid drug delivery due to their capacity to aggrandize the targeting efficacy and therapeutic outcomes of encapsulated drugs. A disadvantage of NDDS is that repeated administrations often encounter an obstacle known as the "accelerated blood clearance (ABC) phenomenon". This phenomenon results in the rapid clearance of the secondary dose from the bloodstream and markedly augmented liver accumulation, which substantially undermines the accurate delivery of drugs and the therapeutic effect of NDDS. Nevertheless, the underlying mechanism of this phenomenon has not been elucidated and there is currently no effective method for its eradication. In light of the above, the aim of this review is to provide a comprehensive summary of the underlying mechanism and potential countermeasures of the ABC phenomenon, with a view to rejuvenating both the slow-release property and expectation of NDDS in the clinic. In this paper, we innovatively introduce the pharmacokinetic mechanism of ABC phenomenon to further elucidate its occurrence mechanism after discussing its immunological mechanism, which provides a new direction for expanding the mechanistic study of ABC phenomenon. Whereafter, we conducted a critical conclusion of potential strategies for the suppression or prevention of the ABC phenomenon in terms of the physical and structural properties, PEG-lipid derivatives, dosage regimen and encapsulated substances of nanoformulations, particularly covering some novel high-performance nanomaterials and mixed modification methods. Alternatively, we innovatively propose a promising strategy of applying the characteristics of ABC phenomenon, as the significantly elevated hepatic accumulation and activated CYP3A1 profile associated with the ABC phenomenon are proved to be conducive to enhancing the efficacy of NDDS in the treatment of hepatocellular carcinoma. Collectively, this review is instructive for surmounting or wielding the ABC phenomenon and advancing the clinical applications and translations of NDDS.

The human retina is a fragile and sophisticated light-sensitive tissue in the central nervous system. Unhealthy retinas can cause irreversible visual deterioration and permanent vision loss. Effective therapeutic strategies are restricted to the treatment or reversal of these conditions. In recent years, nanoscience and nanotechnology have revolutionized targeted management of retinal diseases. Pharmaceuticals, theranostics, regenerative medicine, gene therapy, and retinal prostheses are indispensable for retinal interventions and have been significantly advanced by nanomedical innovations. Hence, this review presents novel insights into the use of versatile nanomaterial-based nanocomposites for frontier retinal applications, including non-invasive drug delivery, theranostic contrast agents, therapeutic nanoagents, gene therapy, stem cell-based therapy, retinal optogenetics and retinal prostheses, which have mainly been reported within the last 5 years. Furthermore, recent progress, potential challenges, and future perspectives in this field are highlighted and discussed in detail, which may shed light on future clinical translations and ultimately, benefit patients with retinal disorders.

Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and recurrence, along with a low sensitivity to immunotherapy, resulting in a paucity of effective therapeutic strategies. Herein, we have developed polydopamine-coated zinc-copper bimetallic nanoplatforms (Cu-ZnO₂@PDA nanoplatforms, abbreviated CZP NPs) that can efficiently induce photothermal amplified cuproptosis and cGAS-STING signaling pathway activation, thereby reversing the immunosuppressive tumor microenvironment of TNBC, upregulating PD-L1 expression, and boosting the efficacy of anti-programmed death-ligand 1 antibody (αPD-L1)-based immunotherapy. Within the acidic tumor microenvironment (TME), CZP NPs spontaneously release copper and zinc ions and hydrogen peroxide, generating highly oxidative hydroxyl radicals and downregulating iron-sulfur cluster proteins. These actions lead to the disruption of mitochondrial integrity, the release of mitochondrial DNA (mtDNA) and irreversible cuproptosis. The further synergy between mtDNA and zinc ions potentiates the activation of the cGAS-STING signaling pathway, triggering a robust antitumor immune response and sensitizing TNBC to αPD-L1 therapy. Additionally, using an 808 nm near-infrared laser for photothermal therapy significantly augments these effects, resulting in a cascade amplification of therapeutic efficacy against TNBC. The strategic combination of CZP NPs with αPD-L1 markedly bolsters antitumor immunity and suppresses tumor growth. Collectively, our findings present a promising synergistic strategy for TNBC treatment by linking cuproptosis, cGAS-STING activation, photothermal therapy, and immunotherapy.

Cold atmospheric plasma (CAP) has exhibited exciting potential for cancer treatment. Reactive oxygen and nitrogen species (RONS), the primary constituents in CAP, contribute to cancer cell death by elevating oxidative stress in cells. However, several intrinsic cellular antioxidant defense systems exist, such as the glutathione peroxidase 4 (GPX4) enzyme, which dampens the cell-killing efficacy of CAP. RAS-selective lethal 3 (RSL3), also known as a ferroptosis inducer, is a synthetic GPX4 inhibitor. Therefore, we hypothesized that RSL3 can amplify CAP-induced cell death by inhibition of GPX4. In this study, we showed that RSL3 loaded in poly (ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG) nanoparticles can enhance CAP-induced cell deaths in 4T1 tumor cells. Furthermore, the combination of CAP and RSL3 also promoted cancer immunogenic cell death (ICD), induced dendritic cell (DC) maturation, and macrophage polarization, initiating tumor-specific T-cell mediated immune responses against tumors. For in vivo application, RSL3@NP was co-delivered with CAP via injectable Pluronic hydrogel. In 4T1-bearing mice, hydrogel-mediated delivery of CAP and RSL3-loaded nanoparticles can effectively elicit potent anti-tumor immune responses and inhibit tumor growth.

Neutrophils play a critical role in the cancer-immunity cycle and are associated with poor clinical outcomes. Recent research has primarily focused on the targeted delivery, phenotypic reversal, and reprogramming of tumor-associated neutrophils, while the impact of disease-associated neutrophils (DANs) on antitumor therapy remains understudied. Since liposomes, as drug delivery carriers, possess excellent biocompatibility and stability, making them particularly suitable for combination therapy, we optimized the formulation of asymmetrically branched polyethylene glycol-modified mitomycin C lipid prodrug liposomes (PEG_2,5 K@MLP-L) and prepared hyaluronic acid and sialic acid ester stearate-co-modified dexamethasone palmitate liposomes (HA*SAS@DXP-L) to study DANs in normal, obese, aged, and septic mice. An increase in mitochondria and lysosomes in Ly-6G⁺CXCR2^high DANs accelerated drug clearance, reduced CD3⁺CD8⁺ T cell activity in tumor-draining lymph nodes, and decreased CD8⁺ T cell infiltration in tumors. As the proportion of DANs increased, the efficacy of PEG_2,5 K@MLP-L decreased. Combination therapy with PEG_2,5 K@MLP-L and HA*SAS@DXP-L can reshape DANs, promote the cancer-immunity cycle, and enhance treatment efficacy. This study identifies key characteristics and functions of DANs and presents a promising strategy for improving clinical outcomes.

It is urgent to exploit multifunctional materials and combined approaches for efficient antitumor effects. Copper-based metal-organic frameworks (Cu-MOFs) have excellent performances in catalysis, biocompatibility, photothermal conversion, and regulate metabolism, which make them attract more and more attention in antitumor application. Therefore, in this review, representative ligands, synthetic methods, antitumor mechanism, and antitumor applications of Cu-MOFs were provided. Special emphasis is placed on the recent antitumor applications of Cu-MOFs in drug carriers, antitumor therapy, tumor imaging, and theranostic, which are summarized with examples. Finally, we presented the dilemma faced by Cu-MOFs and offered a new perspective for future antitumor application. Hopefully, this review may serve as a reference for further development and application of Cu-MOFs.

Diabetes represents a global health crisis that necessitates advancements in prevention, treatment, and management. Beyond glucose regulation, addressing weight management and associated complications is imperative. This study introduces an oral nanoparticle formulation designed to simultaneously control blood glucose, obesity, and metabolic dysfunction. These nanoparticles, based on poly (zwitterion-cholic acid), incorporate a polyzwitterion component to enhance permeation through the mucus layer and prolong drug residence. Furthermore, bile acid polymers not only regulate lipid metabolism but also ameliorate obesity-associated inflammation in adipose and liver tissues. In vivo experiments demonstrated significant hypoglycemic effects in healthy, type I diabetic, and type II diabetic mice. Notably, the nanocarriers significantly reduced body weight gain, ameliorated inflammation in adipose and liver tissues, and modulated lipid metabolism in the liver of db/db mice. Our study elucidates a comprehensive strategy for addressing glycemic control and diabetes-related complications, offering a promising approach for diabetes prevention and treatment.

Small interfering RNA (siRNA) therapies hold great potential for treating myocardial ischemia-reperfusion injury (MIRI); while their practical application is limited by the low bioavailability, off-target effects, and poor therapeutic efficacy. Here, we present an innovative engineered neutrophil membrane-camouflaged nanocomplex for targeted siRNA delivery and effective MIRI therapy. A nanoparticle (NP)-based siRNA delivery system, namely MNM/siRNA NPs, is camouflaged with neutrophil membranes modified by hemagglutinin (HA) and integrins. Our comprehensive in vitro studies show that MNM/siRNA NPs effectively facilitate endosomal escape through HA, achieve excellent targeting via integrins, and significantly reduce integrin α9 expression. Furthermore, in MIRI mice, we identify integrin α9 as a potential target for MIRI therapy and demonstrate that MNM/siRNA NPs significantly decrease myocardial infarction area and improve cardiac function by reducing neutrophil recruitment, neutrophil extracellular trap (NET) and microthrombus formation. These findings highlight the engineered membrane-camouflaged NPs as a promising siRNA delivery platform, offering an effective treatment strategy for MIRI.

Tumor immunotherapy aims to harness the immune system to identify and eliminate cancer cells. However, its full potential is hindered by the immunosuppressive nature of tumors. Radiotherapy remains a key treatment modality for local tumor control and immunomodulation within the tumor microenvironment. Yet, the efficacy of radiotherapy is often limited by tumor radiosensitivity, and traditional radiosensitizers have shown limited effectiveness in hepatocellular carcinoma (HCC). To address these challenges, we developed a novel multifunctional nanoparticle system, ZIF-8@MnCO@DOX (ZMD), designed to enhance drug delivery to tumor tissues. In the tumor microenvironment, Zn²⁺ and Mn²⁺ ions released from ZMD participate in a Fenton-like reaction, generating reactive oxygen species (ROS) that promote tumor cell death and improve radiosensitivity. Additionally, the release of doxorubicin (DOX)-an anthracycline chemotherapeutic agent-induces DNA damage and apoptosis in cancer cells. The combined action of metal ions and double-stranded DNA (dsDNA) from damaged tumor cells synergistically activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, thereby initiating a robust anti-tumor immune response. Both in vitro and in vivo experiments demonstrated that ZMD effectively activates the cGAS-STING pathway, promotes anti-tumor immune responses, and exerts a potent tumor-killing effect in combination with radiotherapy, leading to regression of both primary tumors and distant metastases. Our work provides a straightforward, safe, and effective strategy for combining immunotherapy with radiotherapy to treat advanced cancer.

Uncontrolled deep bleeding, commonly encountered in surgical procedures, combat injuries, and trauma, poses a significant threat to patient survival and recovery. The development of effective hemostatic agents capable of precisely targeting trauma sites in deep tissues and rapidly halt bleeding remains a considerable challenge. Drawing inspiration from the natural hemostatic cascade, we present platelet-like microspheres composed of silk fibroin (SF) and thrombus-targeting peptides, engineered to mimic natural platelets for rapid hemostasis in vivo. These peptide/SF hemostatic microspheres, formulated using a freezing self-assembly technology, closely resemble natural platelets in terms of size, shape, and zeta potential. Moreover, they exhibit favorable cytocompatibility, hemocompatibility, and anti-cell adhesion. Assessment of fibrin polymerization revealed that these hemostatic microspheres possessed enzymatic physiological functions, similar to activated platelets, facilitating platelet adhesion, fibrin binding, and wound-triggered hemostasis. Notably, these hemostatic microspheres rapidly target the bleeding site in vivo within 5 min, with minimal dispersion elsewhere, persisting after blood clot formation. Furthermore, these microspheres exhibit favorable metabolic kinetics, with 71% degradation occurring within one-day post-subcutaneous injection. Histological assessment revealed well-preserved organ structures and minimal inflammatory responses at 14 d post-injection, supporting their long-term biocompatibility. Importantly, they can be injected and targeted into damaged blood vessels, selectively binding to fibrin and forming blood clots within 2 min, resulting in a 74% reduction in bleeding volume compared to SF microspheres alone. Therefore, these injectable SF-based hemostatic microspheres emerge as promising candidates for future rapid hemostasis in tissue injuries.