Stimuli-responsive nanodelivery systems for amplifying immunogenic cell death in cancer immunotherapy.

Immunogenic cell death (ICD) is a special pattern of tumor cell death, enabling to elicit tumor-specific immune response via the release of damage-associated molecular patterns and tumor-associated antigens in the tumor microenvironment. ICD-induced immunotherapy holds the promise for completely eliminating tumors and long-term protective antitumor immune response. Increasing ICD inducers have been discovered for boosting antitumor immunity via evoking ICD. Nonetheless, the utilization of ICD inducers remains insufficient owing to serious toxic reactions, low localization efficiency within the tumor microenvironmental niche, etc. For overcoming such limitations, stimuli-responsive multifunctional nanoparticles or nanocomposites with ICD inducers have been developed for improving immunotherapeutic efficiency via lowering toxicity, which represent a prospective scheme for fostering the utilization of ICD inducers in immunotherapy. This review outlines the advances in near-infrared (NIR)-, pH-, redox-, pH- and redox-, or NIR- and tumor microenvironment-responsive nanodelivery systems for ICD induction. Furthermore, we discuss their clinical translational potential. The progress of stimuli-responsive nanoparticles in clinical settings depends upon the development of biologically safer drugs tailored to patient needs. Moreover, an in-depth comprehending of ICD biomarkers, immunosuppressive microenvironment, and ICD inducers may accelerate the advance in smarter multifunctional nanodelivery systems to further amplify ICD.

Renal Clearable Nanodots-Engineered Erythrocytes with Enhanced Circulation and Tumor Accumulation for Photothermal Therapy of Hepatocellular Carcinoma.

Living cell-mediated nanodelivery system is considered a promising candidate for targeted antitumor therapy; however, their use is restricted by the adverse interactions between carrier cells and nanocargos. Herein, a novel erythrocyte-based nanodelivery system is developed by assembling renal-clearable copper sulfide (CuS) nanodots on the outer membranes of erythrocytes via a lipid fusion approach, and demonstrate that it is an efficient photothermal platform against hepatocellular carcinoma. After intravenous injection of the nanodelivery system, CuS nanodots assembled on erythrocytes can be released from the system, accumulate in tumors in response to the high shear stress of bloodstream, and show excellent photothermal antitumor effect under the near infrared laser irradiation. Therefore, the erythrocyte-mediated nanodelivery system holds many advantages including prolonged blood circulation duration and enhanced tumor accumulation. Significantly, the elimination half-life of the nanodelivery system is 74.75 ± 8.77 h, which is much longer than that of nanodots (33.56 ± 2.36 h). Moreover, the other two kinds of nanodots can be well assembled onto erythrocytes to produce other erythrocyte-based hitchhiking platforms. Together, the findings promote not only the development of novel erythrocyte-based nanodelivery systems as potential platforms for tumor treatment but also their further clinical translation toward personalized healthcare.

Nano-therapeutics: The upcoming nanomedicine to treat cancer.

Nanotechnology is considered a successful approach for cancer diagnosis and treatment. Preferentially, cancer cell recognition and drug targeting via nano-delivery system include the penetration of anticancer agents into the cell membrane to damage the cancer cell by protein modification, DNA oxidation, or mitochondrial dysfunction. The past research on nano-delivery systems and their target has proven the beneficial achievement in a malignant tumor. Modern perceptions using inventive nanomaterials for cancer management have been offered by a multifunctional platform based on various nano-carriers with the probability of imaging and cancer therapy simultaneously. Emerging nano-delivery systems in cancer therapy still lack knowledge of the biological functions behind the interaction between nanoparticles and cancer cells. Since the potential of engineered nanoparticles addresses the various challenges, limiting the success of cancer therapy subsequently, it is a must to review the molecular targeting of a nano-delivery system to enhance the therapeutic efficacy of cancer. This review focuses on using a nano-delivery system, an imaging system, and encapsulated nanoparticles for cancer therapy.

Advances in the variations and biomedical applications of stimuli-responsive nanodrug delivery systems.

Chemotherapy is an important cancer treatment modality, but the clinical utility of chemotherapeutics is limited by their toxic side effects, inadequate distribution and insufficient intracellular concentrations. Nanodrug delivery systems (NDDSs) have shown significant advantages in cancer diagnosis and treatment. Variable NDDSs that respond to endogenous and exogenous triggers have attracted much research interest. Here, we summarized nanomaterials commonly used for tumor therapy, such as peptides, liposomes, and carbon nanotubes, as well as the responses of NDDSs to pH, enzymes, magnetic fields, light, and multiple stimuli. Specifically, well-designed NDDSs can change in size or morphology or rupture when induced by one or more stimuli. The varying responses of NDDSs to stimulation contribute to the molecular design and development of novel NDDSs, providing new ideas for improving drug penetration and accumulation, inhibiting tumor resistance and metastasis, and enhancing immunotherapy.

Critical Review: Uptake and Translocation of Organic Nanodelivery Vehicles in Plants.

Nanodelivery vehicles (NDVs) are engineered nanomaterials (ENMs) that, within the agricultural sector, have been investigated for their ability to improve uptake and translocation of agrochemicals, control release, or target specific tissues or subcellular compartments. Both inorganic and organic NDVs have been studied for agrochemical delivery in the literature, but research on the latter has been slower to develop than the literature on the former. Since the two classes of nanomaterials exhibit significant differences in surface chemistry, physical deformability, and even colloidal stability, trends that apply to inorganic NDVs may not hold for organic NDVs, and vice versa. We here review the current literature on the uptake, translocation, biotransformation, and cellular and subcellular internalization of organic NDVs in plants following foliar or root administration. A background on nanomaterials and plant physiology is provided as a leveling ground for researchers in the field. Trends in uptake and translocation are examined as a function of NDV properties and compared to those reported for inorganic nanomaterials. Methods for assessing fate and transport of organic NDVs in plants (a major bottleneck in the field) are discussed. We end by identifying knowledge gaps in the literature that must be understood in order to rationally design organic NDVs for precision agrochemical nanodelivery.

Nanoparticle-mediated cell pyroptosis: a new therapeutic strategy for inflammatory diseases and cancer.

Pyroptosis, a lytic form of cell death mediated by the gasdermin family, is characterized by cell swelling and membrane rupture. Inducing pyroptosis in cancer cells can enhance antitumor immune responses and is a promising strategy for cancer therapy. However, excessive pyroptosis may trigger the development of inflammatory diseases due to immoderate and continuous inflammatory reactions. Nanomaterials and nanobiotechnology, renowned for their unique advantages and diverse structures, have garnered increasing attention owing to their potential to induce pyroptosis in diseases such as cancer. A nano-delivery system for drug-induced pyroptosis in cancer cells can overcome the limitations of small molecules. Furthermore, nanomedicines can directly induce and manipulate pyroptosis. This review summarizes and discusses the latest advancements in nanoparticle-based treatments with pyroptosis among inflammatory diseases and cancer, focusing on their functions and mechanisms and providing valuable insights into selecting nanodrugs for pyroptosis. However, the clinical application of these strategies still faces challenges owing to a limited understanding of nanobiological interactions. Finally, future perspectives on the emerging field of pyroptotic nanomaterials are presented.

Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization.

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.

Synergistic mechanism of botanical pesticide camptothecin encapsulated in a nanocarrier against fall armyworm: Enhanced stability and amplified growth suppression.

Botanical pesticides are one of the most promising alternatives to synthetic insecticides for green pest management. However, their efficacies must be further improved to meet real needs. Here we designed a nanoscale camptothecin (CPT) encapsulated in a star polycation (SPc) and determined its bioactivity against a devastating agricultural pest, Spodoptera frugiperda. The self-assembly of CPT/SPc complex was mainly driven by hydrogen bonding and Van der Waals forces to decrease the particle size from 789 to 298 nm. With the help of SPc, the contact angle of CPT decreased from 116° to 92° on maize leaves, and its retention was increased from 5.53 to 11.97 mg/cm2. The stability of SPc-loaded CPT was also improved in an alkaline environment, which is beneficial for its acting in lepidopteran insect guts. The CPT/SPc complex had stronger larvicidal activity and ovicidal activity against S. frugiperda than CPT alone, led to more complex transcriptomic changes in larvae, and had obvious adverse impacts on the activities of two digestive enzymes. Our findings demonstrated that the encapsulation of CPT by SPc-based nanodelivery system enabled better insecticidal activities against S. frugiperda, which holds great promise for the development of more efficient and sustainable pest control strategies to meet the demands of modern crop protection.

Brassica-derived isothiocyanates as anticancer therapeutic agents and their nanodelivery.

The isothiocyanates (ITCs) derived from the precursor glucosinolate molecules present in Brassica vegetables are bioactive organo-sulfur compounds with numerous pharmacologically important properties such as antioxidant, antiinflammatory, antimicrobial, and anticancer. Over the years, ITCs have been the focus of several research investigations associated with cancer treatment. Due to their potent chemo-preventive action, ITCs have been considered to be promising therapeutics for cancer therapy in place of the already existing conventional anticancer drugs. However, their wide spread use at the clinical stage is greatly restricted due to several factors such as low solubility in an aqueous medium, low bioavailability, low stability, and hormetic effect. To overcome these hindrances, nanotechnology can be exploited to develop nano-scale delivery systems that have the potential to enhance stability, and bioavailability and minimize the hermetic effect of ITCs.

Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells.

AIM: To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects. METHODS: Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip. RESULTS: BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity. CONCLUSION: BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.

Enhanced Efficacy against Drug-Resistant Tumors Enabled by Redox-Responsive Mesoporous-Silica-Nanoparticle-Supported Lipid Bilayers as Targeted Delivery Vehicles.

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits.

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 µM, 5 µM, and 10 µM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

What we know on the potential use of exosomes for nanodelivery.

Antitumor therapy is taking into consideration the possibility to use natural nanovesicles, called exosomes, as an ideal delivery for both old and new anti-cancer molecules. This with the attempt to improve the efficacy, at the same time reducing the systemic toxicity of physical, chemical, and biological molecules. Exosomes may in fact increase the level of biomimetism, through simulating what really occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use to this purpose, also by analogy with the diffusely used artificial nanoparticles, such as lyposomes. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, while those released by cells in pathological condition, such as tumors may induce undesired, dangerous, and mostly unknown effects. To date we have many pre-clinical data available and possibly useful to think about a strategic use of exosomes as a delivery nanodevice in cancer treatment. However, this review wants to critically emphasize two important points actually hampering further discussion in the field : (i) the clinical data are virtually absent at the moment ; (ii) the best cellular source of exosomes to be used to deliver drugs is really far to be defined. Facing off these two points may well facilitate the attempt to figure out this very important issue for improving at the best future anti-cancer treatments.

Targeted therapy using nanocomposite delivery systems in cancer treatment: highlighting miR34a regulation for clinical applications.

The clinical application of microRNAs in modern therapeutics holds great promise to uncover molecular limitations and conquer the unbeatable castle of cancer metastasis. miRNAs play a decisive role that regulating gene expression at the post-transcription level while controlling both the stability and translation capacity of mRNAs. Specifically, miR34a is a master regulator of the tumor suppressor gene, cancer progression, stemness, and drug resistance at the cell level in p53-dependent and independent signaling. With changing, trends in nanotechnology, in particular with the revolution in the field of nanomedicine, nano drug delivery systems have emerged as a prominent strategy in clinical practices coupled with miR34a delivery. Recently, it has been observed that forced miR34a expression in human cancer cell lines and model organisms limits cell proliferation and metastasis by targeting several signaling cascades, with various studies endorsing that miR34a deregulation in cancer cells modulates apoptosis and thus requires targeted nano-delivery systems for cancer treatment. In this sense, the present review aims to provide an overview of the clinical applications of miR34a regulation in targeted therapy of cancer.

Graphene as a nano-delivery vehicle in agriculture - current knowledge and future prospects.

Graphene has triggered enormous interest in, and exploration of, its applications in diverse areas of science and technology due to its unique properties. While graphene has displayed great potential as a nano-delivery system for drugs and biomolecules in biomedicine, its application as a nanocarrier in agriculture has only begun to be explored. Conventional fertilizers and agricultural delivery systems have a number of disadvantages, such as: fast release of the active ingredient, low delivery efficiency, rapid degradation and low stability that often leads to their over-application and consequent environmental problems. Advanced nano fertilizers with high carrier efficiency and slow and controlled release are now considered the gold standard for promoting agricultural sustainability while protecting the environment. Graphene's attractive properties include large surface area, chemical stability, mechanical stability, tunable surface chemistry and low toxicity making it a promising material on which to base agricultural delivery systems. Recent research has demonstrated considerable success in the use of graphene for agricultural applications, including its utilization as a delivery vehicle for plant nutrients and crop protection agents, as well as in post-harvest management of crops. This review, therefore, presents a comprehensive overview of the current status of graphene-based nanocarriers in agriculture. Additionally, the review outlines the surface functionalization methods used for effective molecular delivery, various strategies for nano-vehicle design and the underlying features necessary for a graphene-based agro-delivery system. Finally, the review discusses directions for further research in optimization of graphene-based nanocarriers.

A Meta-analysis on the Effectiveness of Extracellular Vesicles as Nanosystems for Targeted Delivery of Anticancer Drugs.

While the efficacy of anticancer drugs is hampered by low bioavailability and systemic toxicity, the uncertainty remains whether encapsulation of these drugs into natural nanovesicles such as extracellular vesicles (EVs) could improve controlled drug release and efficacy for targeted tumor therapy. Thus, we performed a meta-analysis for studies reporting the efficacy of EVs as nanosystems to deliver drugs and nucleic acid, protein, and virus (NPV) to tumors using the random-effects model. The electronic search of articles was conducted through Cochrane, PubMed, Scopus, Science Direct, and Clinical Trials Registry from inception up till September 2022. The pooled summary estimate and 95% confidence interval of tumor growth inhibition, survival, and tumor targeting were obtained to assess the efficacy. The search yielded a total of 119 studies that met the inclusion criteria having only 1 clinical study. It was observed that the drug-loaded EV was more efficacious than the free drug in reducing tumor volume and weight with the standardized mean difference (SMD) of -1.99 (95% CI: -2.36, -1.63; p < 0.00001) and -2.12 (95% CI: -2.48, -1.77; p < 0.00001). Similarly, the mean estimate of tumor volume and weight for NPV were the following: SMD: -2.30, 95% CI: -3.03, -1.58; p < 0.00001 and SMD: -2.05, 95% CI: -2.79, -1.30; p < 0.00001. Treatment of tumors with EV-loaded anticancer agents also prolonged survival (HR: 0.15, 95% CI: 0.10, 0.22, p < 0.00001). Furthermore, EVs significantly delivered drugs to tumors as revealed by the higher concentration at the tumor site (SMD: -2.73, 95% CI: -3.77, -1.69; p < 0.00001). This meta-analysis revealed that EV-loaded drugs and NPV performed significantly better in tumor growth inhibition with improved survival than the free anticancer agents, suggesting EVs as safe nanoplatforms for targeted tumor therapy.

New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder affecting a major class of silver citizens. The disorder shares a mutual relationship on account of its cellular and molecular pathophysiology with type-II diabetes mellitus (DM). Chronic DM increases the risk for AD. Emerging evidence recommended that resistance in insulin production develops cognitive dysfunction, which generally leads to AD. Repurposing of antidiabetic drugs can be effective in preventing and treatment of the neurodegenerative disorder. Limitations of antidiabetic drugs restrict the repurposing of the drugs for other disorders. Therefore, nanotechnological intervention plays a significant role in the treatment of neurological disorders. In this review, we discuss the common cellular and molecular pathophysiologies between AD and type-II DM, the relevance of in vivo models of type II DM in the study of AD, and the repurposing of antidiabetic drugs and the nanodelivery systems of antidiabetic drugs against AD.

Potential in exosome-based targeted nano-drugs and delivery vehicles for posterior ocular disease treatment: from barriers to therapeutic application.

Posterior ocular disease, a disease that accounts for 55% of all ocular diseases, can contribute to permanent vision loss if left without treatment. Due to the special structure of the eye, various obstacles make it difficult for drugs to reach lesions in the posterior ocular segment. Therefore, the development of highly permeable targeted drugs and delivery systems is particularly important. Exosomes are a class of extracellular vesicles at 30-150 nm, which are secreted by various cells, tissues, and body fluids. They carry various signaling molecules, thus endowing them with certain physiological functions. In this review, we describe the ocular barriers and the biogenesis, isolation, and engineering of exosomes, as exosomes not only have pharmacological effects but also are good nanocarriers with targeted properties. Moreover, their biocompatibility and immunogenicity are better than synthetic nanocarriers. Most importantly, they may have the ability to pass through the blood-eye barrier. Thus, they may be developed as both targeted nano-drugs and nano-delivery vehicles for the treatment of posterior ocular diseases. We focus on the current status and potential application of exosomes as targeted nano-drugs and nano-delivery vehicles in posterior ocular diseases.

Research advances in citrus polyphenols: green extraction technologies, gut homeostasis regulation, and nano-targeted delivery system application.

Citrus polyphenols can modulate gut microbiota and such bi-directional interaction that can yield metabolites such as short-chain fatty acids (SCFAs) to aid in gut homeostasis. Such interaction provides citrus polyphenols with powerful prebiotic potential, contributing to guts' health status and metabolic regulation. Citrus polyphenols encompass unique polymethoxy flavonoids imparting non-polar nature that improve their bioactivities and ability to penetrate the blood-brain barrier. Green extraction technology targeting recovery of these polyphenols has received increasing attention due to its advantages of high extraction yield, short extraction time, low solvent consumption, and environmental friendliness. However, the low bioavailability of citrus polyphenols limits their applications in extraction from citrus by-products. Meanwhile, nano-encapsulation technology may serve as a promising approach to improve citrus polyphenols' bioavailability. As citrus polyphenols encompass multiple hydroxyl groups, they are potential to interact with bio-macromolecules such as proteins and polysaccharides in nano-encapsulated systems that can improve their bioavailability. This multifaceted review provides a research basis for the green and efficient extraction techniques of citrus polyphenols, as well as integrated mechanisms for its anti-inflammation, alleviating metabolic syndrome, and regulating gut homeostasis, which is more capitalized upon using nano-delivery systems as discussed in that review to maximize their health and food applications.

Mesoporous polydopamine delivering 8-gingerol for the target and synergistic treatment to the spinal cord injury.

In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.