Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.

Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.

Effect of body mass index (BMI) on image contrast in the hepatobiliary phase of Gd-EOB-DTPA-enhanced-MRI and the feasibility of the application of half-dose Gd-EOB-DTPA to hepatobiliary phase imaging in patients with a BMI less than 24: a comparative study.

Background: Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect more lesions through the image contrast of hepatobiliary phase. Body mass index (BMI) reflects the composition ratio of human tissue, which is an influencing factor of magnetic resonance image contrast. Meanwhile, Gd-EOB-DTPA is recommended to use the minimum dose when the diagnosis demands could be met. The aim of this paper was to investigate the effect of BMI on hepatobiliary phase image contrast and explore the feasibility of using low-dose Gd-EOB-DTPA to obtain good hepatobiliary phase image contrast in patients with normal and lean BMI. Methods: Eighty-two patients who had previously undergone Gd-EOB-DTPA-enhanced MRI (0.025 mmol/kg) were collected and divided into group A (BMI <24 kg/m2) and group B (BMI ≥24 kg/m2) according to Chinese BMI standards. Liver-to-portal vein contrast ratio (LPC20) and liver-to-spleen contrast ratio (LSC20) in hepatobiliary phase (20 min after injection) were calculated. Thirty patients with a BMI <24 kg/m2 who were about to receive Gd-EOB-DTPA-enhanced MRI were randomly divided into group C (0.0125 mmol/kg) and group D (0.025 mmol/kg). Image acquisition was performed at 10, 15, and 20 min after injection. LPC10, LPC15, LPC20 and LSC10, LSC15, LSC20 in corresponding phases were calculated. Results: In retrospective grouping study, compared with group B, group A's LPC20 was significantly higher [2.63 (2.42-3.00) vs. 2.22 (1.97-2.67); P<0.01]. In prospective grouping study, there were no differences in LPC15, LSC15, LPC20 and LSC20 between group C and group D. Intragroup comparison in each group showed that LPC15 (group C: 2.67±0.33; group D: 2.61±0.21) and LPC20 (group C: 2.74±0.37; group D: 2.72±0.27) were higher than LPC10 (group C: 2.19±0.18; group D: 1.94±0.17) (all P<0.01), while there were no changes between LPC15 and LPC20. Conclusions: Under conventional dose, hepatobiliary phase image contrast in patients with a BMI <24 was higher, which was mainly manifested in the high LPC. For patients with a BMI <24 kg/m2, using a half conventional dose (0.0125 mmol/kg), good hepatobiliary phase image contrast can still be obtained at 15-20 min after administration.

Poly(ether ether ketone) Conferred Polyolefin Separators with High Dimensional Thermal Stability for Lithium-Ion Batteries.

The traditional polyolefin separators used in lithium-ion batteries (LIBs) are plagued by limitations such as poor wetting of electrolytes and insufficient thermal stability, hindering the progress of LIBs. To overcome these limitations, we have developed a modified phase inversion technique to efficiently and durably coat polyolefin separators with poly(ether ether ketone) (PEEK). The resulting PEEK-coated polyolefin separators exhibit mechanical properties similar to those of unmodified polyolefin separators, with comparable tensile strength and modulus. Furthermore, the PEEK coating provides outstanding thermal stability, as the modified separators maintain their stability even at temperatures up to 200 °C, which is among the best results reported for polyolefin-based separators. In addition, the PEEK coating enhances ionic conductivity by more than 100% compared to polyolefin counterparts, leading to significant improvement in the electrochemical performance of prototype half cells. The modified phase inversion technique presented here offers a practical solution for coating polyolefin separators with functional polymers, paving the way for next-generation separator materials.

Glutathione-Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy.

Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. Here, a prodrug that releases CPT in response to glutathione (GSH), which is commonly overexpressed by cancer cells is reported. Through assembling with PEGylated lipids, the prodrug is incorporated within as-assembled nanoparticles, affording CPT with a prolonged half-life in blood circulation, enhanced tumor targetingability, and improved therapeutic efficacy. Furthermore, such prodrug nanoparticles can also promote dendritic cell maturation and tumor infiltration of CD8+ T cells, providing a novel strategy to improve the therapeutic efficacy of CPT.

Inflammation-related Gene Polymorphisms Associated With Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. The pathogenesis of inflammation-related single-nucleotide polymorphism (SNP) in children with ALL remains unclear. OBJECTIVE: This study was to discover the association of the SNP sites of some inflammation-related genes and the susceptibility and treatment response of ALL in children, so as to provide personalized treatment for ALL in children. PROCEDURE: One hundred sixty-five childhood ALL patients and 175 age-matched healthy participants were recruited in this study. We investigated the involvement of 31 SNPs of the inflammation-related genes in the pathogenesis and treatment response of childhood ALL. RESULTS: Statistical analysis revealed that rs2280714 in IRF5, rs2297630 in SDF-1, rs4353135 in NLRP3, rs1946518 in interleukin-18 were related to the susceptibility to pediatric ALL. Interleukin-1ß rs16944 SNP was correlated with ALL risk stage in children. Rs7633631 in CD226 and rs10818488 in TRAF1 were related to the minimal residual disease (MRD) on day 15 and day 33. CONCLUSIONS: Certain SNPs of inflammation genes were associated with the susceptibility and treatment response of ALL children. These findings may help in the early detection, diagnostic evaluation, and making individual chemotherapy regimen for ALL children according to the genotype of these sites at the time of initial diagnosis.

The Preeminent Value of the Apparent Diffusion Coefficient in Assessing High-Risk Factors and Prognosis for Stage I Endometrial Carcinoma Patients.

OBJECTIVES: To evaluate the role of the apparent diffusion coefficient (ADC) value in the individualized management of stage I endometrial carcinoma (EC). METHODS: A retrospective analysis was performed on 180 patients with stage I EC who underwent 1.5-T magnetic resonance imaging. The mean ADC (mADC), minimum ADC (minADC), and maximum ADC (maxADC) values of each group were measured and compared. We analyzed the relationship between ADC values and stage I EC prognosis by Kaplan-Meier method and Cox proportional hazards analysis. RESULTS: Patients with lower ADC values were more likely to be characterized by higher grades, specific histological subtypes and deeper myometrial invasion. The mADC, minADC and maxADC values (×10-3 mm2/s) were 1.045, 0.809 and 1.339, respectively, in grade 1/2 endometrioid carcinoma with superficial myometrial invasion, which significantly differed from those in grade 3 or nonendometrioid carcinoma or with deep myometrial invasion (0.929, 0.714 and 1.215) (P=<0.001, <0.001 and <0.001). ADC values could be used to predict these clinicopathological factors. Furthermore, the group with higher ADC values showed better disease-free survival and overall survival. CONCLUSIONS: The present study indicated that ADC values were associated with the high-risk factors for stage I EC and to assess whether fertility-sparing, ovarian preservation or omission of lymphadenectomy represent viable treatment options. Moreover, this information may be applied to predict prognosis. Thus, ADC values could contribute to managing individualized therapeutic schedules to improve quality of life.

Biodegradable Polymer with Effective Near-Infrared-II Absorption as a Photothermal Agent for Deep Tumor Therapy.

Photothermal therapy holds great promise for cancer treatment due to its effective tumor ablation and minimal invasiveness. Herein a new class of biodegradable photothermal agents with effective adsorption in both near-infrared-I (NIR-I) and NIR-II windows is reported for deep tumor therapy. As demonstrated in a deep-seated ovarian cancer model, photothermal therapy using 1064 nm irradiation effectively inhibits tumor progression and prolongs survival spans. This work provides a new design of photothermal agents toward a more effective therapy of tumors.

Radiographic optimization of the lateral position of the knee joint aided by CT images and the maximum intensity projection technique.

BACKGROUND: Standard lateral knee-joint X-ray images are crucial for the accurate diagnosis and treatment of many knee-joint-related conditions. However, it is difficult to obtain standard lateral knee-joint X-ray images in the current knee-joint lateral radiography position. PURPOSE: To optimize the lateral position of knee joint for radiography aided by computed tomography (CT) images and the maximum intensity projection technique. MATERIALS AND METHODS: One hundred cases of anteroposterior and lateral radiographs of knee joints were included. Of these, 50 cases were for lateral radiography in conventional position, and the other 50 cases were for lateral radiography in optimized position. The optimized position was acquired by a retrospective analysis of one hundred cases of knee-joint CT images. The quality of the X-ray images in optimized group was compared with those in conventional group. The data were statistically analyzed using the Mann-Whitney U test. RESULTS: There were differences in the optimized position between males and females. The posterior condyles of the femoral epiphysis in optimized group were in perfect superimposition for most patients. However, the ones in conventional group were not. The average quality score of the lateral knee-joint X-ray images in optimized position was 3.76 ± 0.98, which is much higher than the 1.84 ± 1.15 score in conventional position. Moreover, the difference in the average quality score was statistically significant (P < 0.05). CONCLUSION: Optimization of the lateral position of knee joint for radiography is possible with the aid of CT images and the maximum intensity projection technique.

Predesign of Catalytically Active Sites via Stable Coordination Cluster Model System for Electroreduction of CO2 to Ethylene.

Purposefully designing the well-defined catalysts for the selective electroreduction of CO2 to C2 H4 is an extremely important but challenging work. In this work, three crystalline trinuclear copper clusters (Cu3 -X, X=Cl- , Br- , NO3 - ) have been designed, containing three active Cu sites with the identical coordination environment and appropriate spatial distance, delivering high selectivity for the electrocatalytic reduction of CO2 to C2 H4 . The highest faradaic efficiency of Cu3 -X for CO2 -to-C2 H4 conversion can be adjusted from 31.90 % to 55.01 % by simply replacing the counter anions (NO3 - , Cl- , Br- ). The DFT calculation results verify that Cu3 -X can facilitate the C-C coupling of identical *CHO intermediates, subsequently forming molecular symmetrical C2 H4 product. This work provides an important molecular model system and a new design perspective for electroreduction of CO2 to C2 products with symmetrical molecular structure.

Graphite-Embedded Lithium Iron Phosphate for High-Power-Energy Cathodes.

Lithium iron phosphate (LiFePO4) is broadly used as a low-cost cathode material for lithium-ion batteries, but its low ionic and electronic conductivity limit the rate performance. We report herein the synthesis of LiFePO4/graphite composites in which LiFePO4 nanoparticles were grown within a graphite matrix. The graphite matrix is porous, highly conductive, and mechanically robust, giving electrodes outstanding cycle performance and high rate capability. High-mass-loading electrodes with high reversible capacity (160 mA h g-1 under 0.2 C), ultrahigh rate capability (107 mA h g-1 under 60 C), and outstanding cycle performance (>95% reversible capacity retention over 2000 cycles) were achieved, providing a new strategy toward low-cost, long-life, and high-power batteries. Adoption of such material leads to electrodes with volumetric energy density as high as 427 W h L-1 under 60 C, which is of great interest for electric vehicles and other applications.

Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model.

BACKGROUND: Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rg tm1Wjl /SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions-including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)-due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system. METHODS: We have developed a humanized mouse model using a novel NSG strain, NOD.Cg-Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG-Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44. RESULTS: As expected, xenografted humanized NSG-Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG-Hc1 mice and, more importantly, mediated antilymphoma cellular responses. CONCLUSIONS: These results indicate that NSG-Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.

Development of risk prediction models for lung cancer based on tumor markers and radiological signs.

BACKGROUND: Accurate prediction of malignancy risk for pulmonary lesions with pleural effusion improves early diagnosis of lung cancer. This study aimed to develop and validate a model to predict lung cancer. METHODS: Clinical data of 536 patients with pulmonary diseases were collected. The risk factors were identified by regression analysis. Three prediction models were developed. The predictive performances of the models were measured by the area under the curves (AUCs) and calibrated with 1000 bootstrap samples to minimize the over-fitting bias. The net benefits of the models were evaluated by decision curve analysis. Finally, a separate cohort of 134 patients was used to validate the models externally. RESULTS: Seven independent risk factors were identified from 18 clinical variables, which included the pleural fluid carcinoembryonic antigen (CEA), serum cytokeratin-19 fragment (CYFRA 21-1), the ratio of CEA in the pleural fluid to serum, extrathoracic cancer history (>5 years), tumor size, vessel convergence, and lobulation. The AUCs of the three models were 0.976, 0.927, and 0.944 in the training set and 0.930, 0.845, and 0.944 in the external set, respectively. The accuracies of the three models were 89.6%, 81.4%, and 88.8%. Model 1 showed the best iteration fit (R2  = 0.84, 0.68, and 0.73) and a higher net benefit on decision curve analysis when compared to the other two models. CONCLUSION: The advantageous model could assess the risk of lung cancer in patients with pleural effusion and act as a useful tool for early identification of lung cancer.

Contribution of Ictal Source Imaging for Localizing Seizure Onset Zone in Patients With Focal Epilepsy.

OBJECTIVE: To determine whether seizure onset zone (SOZ) can be localized accurately prior to surgical planning in patients with focal epilepsy, we performed noninvasive EEG recordings and source localization analyses on 39 patients. METHODS: In 39 patients with focal epilepsy, we recorded and extracted 138 seizures and 1,325 interictal epileptic discharges using high-density EEG. We investigated a novel approach for directly imaging sources of seizures and interictal spikes from high-density EEG recordings, and rigorously validated it for noninvasive localization of SOZ determined from intracranial EEG findings and surgical resection volume. Conventional source imaging analyses were also performed for comparison. RESULTS: Ictal source imaging showed a concordance rate of 95% when compared to intracranial EEG or resection results. The average distance from estimation to seizure onset (intracranial) electrodes is 1.35 cm in patients with concordant results, and 0.74 cm to surgical resection boundary in patients with successful surgery. About 41% of the patients were found to have multiple types of interictal activities; coincidentally, a lower concordance rate and a significantly worse performance in localizing SOZ were observed in these patients. CONCLUSION: Noninvasive ictal source imaging with high-density EEG recording can provide highly concordant results with clinical decisions obtained by invasive monitoring or confirmed by resective surgery. By means of direct seizure imaging using high-density scalp EEG recordings, the added value of ictal source imaging is particularly high in patients with complex interictal activity patterns, who may represent the most challenging cases with poor prognosis.

The prominent value of apparent diffusion coefficient in assessing high-risk factors and prognosis for patients with endometrial carcinoma before treatment.

BACKGROUND: To date, there are no consensus methods to evaluate the high-risk factors and prognosis for managing the personalized treatment schedule of patients with endometrial carcinoma (EC) before treatment. Apparent diffusion coefficient (ADC) is regarded as a kind of technique to assess heterogeneity of malignant tumor. PURPOSE: To explore the role of ADC value in assessing the high-risk factors and prognosis of EC. MATERIAL AND METHODS: A retrospective analysis was made on 185 patients with EC who underwent 1.5-T magnetic resonance imaging (MRI). Mean ADC (mADC), minimum ADC (minADC), and maximum ADC (maxADC) were measured and compared in different groups. RESULTS: Among the 185 patients with EC, the mADC and maxADC values in those with high-risk factors (type 2, deep myometrial invasion, and lymph node metastasis) were significantly lower than in those without. According to receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUC) were significant for mADC, minADC, and maxADC predicting high-risk factors. Furthermore, the AUCs were significant for mADC and maxADC predicting lymph node metastasis but were not significant for minADC. Patients with lower mADC were associated with worse overall survival and disease-free survival; the opposite was true for patients with higher mADC. CONCLUSION: Our study showed that ADC values could be applied to assess the high-risk factors of EC before treatment and might significantly relate to the prognosis of EC. It might contribute to managing initial individualized treatment schedule and improve outcome in patients with EC.

3D Hydrangea Macrophylla-like Nickel-Vanadium Metal-Organic Frameworks Formed by Self-Assembly of Ultrathin 2D Nanosheets for Overall Water Splitting.

The development of highly efficient and low-cost bifunctional noble metal-free electrocatalysts for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is an effective strategy for improving efficiency. Herein, novel three-dimensional (3D) bimetallic metal-organic frameworks containing Ni and V with adjustable stoichiometry were synthesized on nickel foam successfully. Notably, Ni2V-MOFs@NF only require rather low overpotentials of 244 and 89 mV for the OER and HER, respectively, and expedites overall water splitting with 1.55 V at 10 mA cm-2 with robust durability during the 80 h test. The high efficiency of the novel obtained electrocatalysts should be attributed to the particular morphological design of the two-dimensional (2D) ultrathin nanosheets self-assembling into a 3D nanoflower and the electronic structure regulation resulting from the synergetic interaction between nickel and vanadium. Subsequent theoretical calculations reveal the following conclusions: (I) the exceptional electronic conductivity of Ni2V-MOFs shows enhanced optimization as a result of electronic structure reconstruction, (II) the energy barrier reduction of the rate-limiting step is responsible for the enhanced dynamics of Ni2V-MOFs for the OER, and (III) the facilitation of the adsorption of H+ and H2O plays a key role in progressing the HER catalytic activity of Ni2V-MOFs.

A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors.

Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tumor cells and the microenvironment. To overcome these limitations, we prepared a novel tumor-targeting delivery system based on the underlying mechanism of immune-targeted cell death that encapsulated granzyme B protein within a porous polymeric nanocapsule. Methods: A cell-penetrating peptide TAT was attached onto granzyme B (GrB) to enhance its transmembrane transport efficiency and potency to induce cell apoptosis. The endocytosis and internalization pathways of GrB-TAT (GrB-T) were analyzed in comparison with perforin by confocal microscopy and flow cytometry. Furthermore, the positively charged GrB-T was wrapped into nanoparticles by p-2-methacryloyloxy ethyl phosphorylcholine (PMPC)-modified HA (hyaluronic acid). The nanoparticles (called TCiGNPs) were characterized in terms of zeta potential and by transmission electron microscopy (TEM). The in vitro anti-tumor effects of GrB-T were examined by cell apoptosis assay and Western blotting analysis. The in vivo anti-tumor therapeutic efficacy of TCiGNPs was evaluated in a mouse tumor model. Results: The TAT peptide could play a role similar to perforin to mediate direct transmembrane transfer of GrB and improve GrB-induced cell apoptosis. The TCiGNPs were successfully synthesized and accumulated in the solid tumor through enhanced permeability and retention (EPR) effect. In the tumor microenvironment, TCiGNPs could be degraded by hyaluronidase and triggered the release of GrB-T. The TAT peptide enabled the translocation of GrB across the plasma membrane to induce tumor cell apoptosis in vivo.Conclusion: We successfully developed a granzyme B delivery system with a GrB-T core and a PMPC/HA shell that simulated CTL/NK cell-mediated cancer immunotherapy mechanism. The GrB delivery system holds great promise for cancer treatment analogous to the CTL/NK cell-induced immunotherapy.

Real-Time Quantification of Cell Internalization Kinetics by Functionalized Bioluminescent Nanoprobes.

Cells transport mass dynamically, crossing cell membranes to maintain metabolism and systemic homeostasis, through which biomolecules are also delivered to cells for gene editing, cell reprograming, therapy, and other purposes. Quantifying the translocation kinetics is fundamentally and clinically essential, but remains limited by fluorescence-based technologies, which are semi-quantitative and only provide kinetics information at cellular level or in discrete time. Herein, a real-time method of quantifying cell internalization kinetics is reported using functionalized firefly-luciferase nanocapsules as the probe. This quantitative assay will facilitate the rational design of delivery vectors and enable high-throughput screening of peptides and other functional molecules, constituting an effective tool for broad applications, including drug development and cancer therapy.

Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice.

Approximately 15-40% of all cancers develop metastases in the central nervous system (CNS), yet few therapeutic options exist to treat them. Cancer therapies based on monoclonal antibodies are widely successful, yet have limited efficacy against CNS metastases, owing to the low levels of the drug reaching the tumour site. Here, we show that the encapsulation of rituximab within a crosslinked zwitterionic polymer layer leads to the sustained release of rituximab as the crosslinkers are gradually hydrolysed, enhancing the CNS levels of the antibody by approximately tenfold with respect to the administration of naked rituximab. When the nanocapsules were functionalized with CXCL13-the ligand for the chemokine receptor CXCR5, which is frequently found on B-cell lymphoma-a single dose led to improved control of CXCR5-expressing metastases in a murine xenograft model of non-Hodgkin lymphoma, and eliminated lymphoma in a xenografted humanized bone marrow-liver-thymus mouse model. Encapsulation and molecular targeting of therapeutic antibodies could become an option for the treatment of cancers with CNS metastases.

In Situ Modification of the Tumor Cell Surface with Immunomodulating Nanoparticles for Effective Suppression of Tumor Growth in Mice.

Current cancer immunotherapies including chimeric antigen receptor (CAR)-based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial-based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune-related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies. Herein, a rational design of immunomodulating nanoparticles is demonstrated that can in situ modify the tumor cell surface with natural killer cell (NK cell)-activating signals to achieve in situ activation of tumor-infiltrating NK cells, as well as direction of their antitumor immunity toward tumor cells. Using these immunomodulating nanoparticles, the remarkable inhibition of tumor growth is observed in mice without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ NK cell activation in tumors. Further development by constructing interactions with various immune cells can potentially make this nanotechnology become a general platform for the design of advanced immunotherapies for cancer treatments.

Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration.

The central nervous system (CNS) plays a central role in the control of sensory and motor functions, and the disruption of its barriers can result in severe and debilitating neurological disorders. Neurotrophins are promising therapeutic agents for neural regeneration in the damaged CNS. However, their penetration across the blood-brain barrier remains a formidable challenge, representing a bottleneck for brain and spinal cord therapy. Herein, a nanocapsule-based delivery system is reported that enables intravenously injected nerve growth factor (NGF) to enter the CNS in healthy mice and nonhuman primates. Under pathological conditions, the delivery of NGF enables neural regeneration, tissue remodeling, and functional recovery in mice with spinal cord injury. This technology can be utilized to deliver other neurotrophins and growth factors to the CNS, opening a new avenue for tissue engineering and the treatment of CNS disorders and neurodegenerative diseases.