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1.
Acta Radiol ; : 284185120940271, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32702999

RESUMO

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.

2.
Nano Lett ; 20(7): 5435-5442, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32491862

RESUMO

High-performance lithium-ion batteries (LIBs) demand efficient and selective transport of lithium ions. Inspired by ion channels in biology systems, lithium-ion channels are constructed by chemically modifying the nanoporous channels of metal-organic frameworks (MOFs) with negatively charged sulfonate groups. Analogous to the biological ion channels, such pendant anionic moieties repel free anions while allowing efficient transport of cations through the pore channels. Implementing such MOFs as an electrolyte membrane doubly enhances the lithium-ion transference number, alleviates concentration polarization, and affords striking durability of high-rate LIBs. This work demonstrates an ion-selective material design that effectively tunes the ion-transport behavior and could assist with more efficient operation of LIBs.

3.
Nanoscale ; 12(26): 13918-13925, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32588865

RESUMO

Particular recent interest has been given to the Li2TiSiO5 (LTSO) anode material owing to its low lithiation potential (0.28 V vs. Li/Li+) and decent theoretical capacity (308 mA h g-1). However, its poor electronic conductivity (∼10-7 S m-1) fundamentally limits the utilization of this material, and current strategies fail to tackle such issues in practical ways. Herein, a hierarchical microparticulate LTSO-carbon composite (LTSO/C) is fabricated by chemical vapor deposition (CVD), where microsized LTSO/C particles assembled from nanospheres guarantee a practical tap density of ∼1.3 g mL-1. Meanwhile, significantly elevated conductivity of LTSO/C (∼103 S m-1) is achieved by a thin layer (15 nm) of graphitic carbon growth on LTSO, which is theoretically catalyzed by the surface functional groups on the parent LTSO. The electrochemical characterization of LTSO/C reveals a superior graphite-like volumetric capacity of 441.1 mA h cm-3 and Li4Ti5O12-like rate capability (120.1 mA h cm-3 at 4.5 A g-1), providing inspiring guidance for designing analogous Ti or Si-based compounds for ultrafast lithium storage materials.

4.
J Colloid Interface Sci ; 577: 48-53, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32464338

RESUMO

Porous carbon materials are promising candidates for anode materials in rechargeable potassium-ion batteries. However, their high surface area and low crystallinity usually cause side reactions with electrolytes and slanted charge/discharge profiles. Herein, we report the synthesis of porous carbon microspheres with highly graphitized structure and enhanced potassium-ion storage properties. The prepared carbon microspheres exhibit a low working potential of ~0.2 V, high Coulombic efficiency, and a stable reversible capacity of 292.0 mAh/g after 100 cycles, which is significantly higher than that of commercial graphite (137.5 mAh/g after 100 cycles). These desirable performances are attributed to the high crystallinity of carbon and its porous structure, which provide active sites for potassium-ion storage and alleviate the stress caused by the large volume change during the insertion and extraction of potassium ions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32463933

RESUMO

Highly effective photocatalysts for the hydrogen-evolution reaction were developed by conferring the linkers of NH2 -MIL-125(Ti), a metal-organic framework (MOF) constructed from TiOx clusters and 2-aminoterephthalic acid (linkers), with active copper centers. This design enables effective transfer of electrons from the linkers to the transient Cu2+ /Cu+ centers, leading to 7000-fold and 27-fold increase of carrier density and lifetime of photogenerated charges, respectively, as well as high-rate production of H2 under visible-light irradiation. This work provides a novel design of a photocatalyst for hydrogen evolution using non-noble Cu2+ /Cu+ as co-catalysts.

6.
Small ; 16(24): e2000794, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32419375

RESUMO

The development of lithium metal anodes capable of sustaining large volume changes, avoiding lithium dendrite formation, and remaining stable in ambient air is crucial for commercially viable lithium metal batteries. Toward this goal, the fabrication of porous and lithiophilic copper scaffolds via a powder metallurgy strategy is reported. Infiltrating the scaffolds with molten lithium followed by exposure to Freon R134a produces lithium metal anodes with dramatically improved rate performance and cycling stability. This work provides a simple yet effective route for the fabrication of safe, low-cost lithium metal batteries with high energy density.

7.
Nat Commun ; 11(1): 1374, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170134

RESUMO

Limited by the size of microelectronics, as well as the space of electrical vehicles, there are tremendous demands for lithium-ion batteries with high volumetric energy densities. Current lithium-ion batteries, however, adopt graphite-based anodes with low tap density and gravimetric capacity, resulting in poor volumetric performance metric. Here, by encapsulating nanoparticles of metallic tin in mechanically robust graphene tubes, we show tin anodes with high volumetric and gravimetric capacities, high rate performance, and long cycling life. Pairing with a commercial cathode material LiNi0.6Mn0.2Co0.2O2, full cells exhibit a gravimetric and volumetric energy density of 590 W h Kg-1 and 1,252 W h L-1, respectively, the latter of which doubles that of the cell based on graphite anodes. This work provides an effective route towards lithium-ion batteries with high energy density for a broad range of applications.

8.
Anal Chem ; 92(8): 5830-5837, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32202407

RESUMO

The present study demonstrates the use of highly stable single-molecule enzyme nanocapsules (SMENs) instead of traditional native enzyme as biorecognition element in enzyme-based biosensors. The main purpose of this study is to resolve the major obstacle and challenge in the biosensor field, i.e., the poor stability of enzyme-based biosensors, including thermal stability, organic solvent tolerance, long-term operational stability, etc. Highly active and robust SMENs of glucose oxidase (GOx, as a model enzyme) were synthesized (nGOx) using an in situ polymerization strategy in an aqueous environment. The particle-size distribution, transmission electron microscopic (TEM) images, and UV-vis spectral characterization revealed the formation of a thin polymer layer around each enzyme molecule. The polymer shell effectively stabilized the GOx enzyme core while enabling rapid substrate transportation, resulting in a new class of biocatalytic nanocapsules. Multiple covalent attachments between a thin polymer layer and an enzyme molecule strengthened the encapsulated GOx molecule. Encapsulation created a favorable microenvironment to avoid any structural dissociation at high temperature and helped to retain essential water during the organic solvent operation. The present work reports a study implementing nGOx SMENs as highly stable nano(bio)sensors for point-of-care diagnostic applications. Prepared nGOx SMENs manifested significantly improved thermal stability (even at 65 °C) and organic solvent tolerance without any compromise in biocatalytic activity. For example, the native GOx-based biosensor lost its catalytic activity for glucose after 4 h of incubation at high temperature (65 °C), while the nGOx/N-CNTs-Chi/GCE nano(bio)sensor maintained ∼56% of its original catalytic activity for glucose oxidation. The proposed SMENs-based nano(bio)sensors with robust stability in variable working environment could promote the development and applications of biosensors in point-of care diagnostics, biomedical detection, wearable devices, implantable equipment, and biofuel cells.

9.
Asian-Australas J Anim Sci ; 33(1): 12-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31480193

RESUMO

OBJECTIVE: The objective of a conservation program is to maintain maximum genetic diversity and preserve the viability of a breed. However, the efficiency of a program is influenced by the ability to accurately measure and predict genetic diversity. METHODS: To examine this question, we conducted a simulation in which common measures (i.e. heterozygosity) and novel measures (identity-by-descent probabilities and parental genomic components) were used to estimate genetic diversity within a conserved population using double-labeled single nucleotide polymorphism markers. RESULTS: The results showed that the accuracy and sensitivity of identity-by-state probabilities and heterozygosity were close to identity by descent (IBD) probabilities, which reflect the true genetic diversity. Expected heterozygosity most closely aligned with IBD. All common measures suggested that practices used in the current Chinese pig conservation program result in a ~5% loss in genetic diversity every 10 generations. Parental genomic components were also analyzed to monitor real-time changes in genomic components for each male and female ancestor. The analysis showed that ~7.5% of male families and ~30% of female families were lost every 5 generations. After 50 generations of simulated conservation, 4 male families lost ~50% of their initial genomic components, and the genomic components for 24.8% of the female families were lost entirely. CONCLUSION: In summary, compared with the true genetic diversity value obtained using double-labeled markers, expected heterozygosity appears to be the optimal indicator. Parental genomic components analysis provides a more detailed picture of genetic diversity and can be used to guide conservation management practices.

10.
Theranostics ; 9(25): 7616-7627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695790

RESUMO

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.

11.
Adv Mater ; 31(39): e1902469, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402525

RESUMO

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.


Assuntos
Luciferases de Vaga-Lume/química , Luciferases de Vaga-Lume/metabolismo , Substâncias Luminescentes/química , Substâncias Luminescentes/metabolismo , Nanocápsulas/química , Animais , Linhagem Celular Tumoral , Cinética , Camundongos , Transporte Proteico
12.
Nat Biomed Eng ; 3(9): 706-716, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31384008

RESUMO

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.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Sistema Nervoso Central , Sistemas de Liberação de Medicamentos/métodos , Linfoma de Células B/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Rituximab/farmacologia , Animais , Encéfalo , Quimiocina CXCL13/efeitos dos fármacos , Quimiocina CXCL13/metabolismo , Modelos Animais de Doenças , Metástase Linfática/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Camundongos , Nanocápsulas , Receptores CXCR5/efeitos dos fármacos , Receptores CXCR5/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Adv Mater ; 31(32): e1902542, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183900

RESUMO

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.


Assuntos
Membrana Celular/imunologia , Fatores Imunológicos/química , Células Matadoras Naturais/metabolismo , Nanopartículas/química , Resinas Acrílicas/química , Animais , Ácidos Borônicos/química , Linhagem Celular Tumoral , Reagentes para Ligações Cruzadas/química , Portadores de Fármacos/química , Imunoglobulina G/química , Imunoterapia , Células Matadoras Naturais/imunologia , Camundongos , Transplante de Neoplasias , Polímeros/química , Soroalbumina Bovina/química , Propriedades de Superfície
14.
ACS Appl Mater Interfaces ; 11(24): 21435-21444, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31117421

RESUMO

Thermally stable porous bimetallic (Ni xPt1- x) alloy mesocrystals within a carbon framework are produced via an aerosol-assisted process for high-performance catalysts for the oxygen reduction reaction (ORR) and hydrogenation. The porous Ni xPt1- x alloy has a robust composite of alloy nanoparticles with an adjustable composition and a porous carbon skeleton. Porous Ni xPt1- x alloys exhibit high thermal stability, retaining their crystalline structure and morphology at 550 °C for 6 h, as observed in thermal treatment tests under various conditions (time, temperature, and atmosphere). The porous Ni xPt1- x alloy as a catalyst for the hydrogenation of propylene has high conversion efficiency (>80%) and low activation energy ( Ea < 20 kJ/mol) at ≥80 °C through the suitable control of the element composition and a pore structure. As a catalyst for the ORR, the catalytic activity of the porous Ni xPt1- x alloy is superior to that of conventional Pt/C (0.115 mA) (0.853 mA/cmPt2 at 0.9 V/cmPt2). This is attributed to the homogeneous alloying of the metal components (Ni and Pt) and the increased accessibility of the reactants to the catalyst, resulting from the unique morphology of the porous Ni xPt1- x alloy, i.e., hierarchical structure with high porosity.

15.
Adv Mater ; 31(33): e1900727, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125138

RESUMO

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.


Assuntos
Barreira Hematoencefálica/metabolismo , Nanocápsulas/química , Fatores de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Barreira Hematoencefálica/ultraestrutura , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Injeções Intravenosas , Macaca mulatta , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/administração & dosagem , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/líquido cefalorraquidiano , Células PC12 , Permeabilidade , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Poliésteres/química , Ratos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
16.
Nat Commun ; 10(1): 1474, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30931924

RESUMO

The application of graphene for electrochemical energy storage has received tremendous attention; however, challenges remain in synthesis and other aspects. Here we report the synthesis of high-quality, nitrogen-doped, mesoporous graphene particles through chemical vapor deposition with magnesium-oxide particles as the catalyst and template. Such particles possess excellent structural and electrochemical stability, electronic and ionic conductivity, enabling their use as high-performance anodes with high reversible capacity, outstanding rate performance (e.g., 1,138 mA h g-1 at 0.2 C or 440 mA h g-1 at 60 C with a mass loading of 1 mg cm-2), and excellent cycling stability (e.g., >99% capacity retention for 500 cycles at 2 C with a mass loading of 1 mg cm-2). Interestingly, thick electrodes could be fabricated with high areal capacity and current density (e.g., 6.1 mA h cm-2 at 0.9 mA cm-2), providing an intriguing class of materials for lithium-ion batteries with high energy and power performance.

17.
Adv Mater ; 31(21): e1808338, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30957302

RESUMO

Novel composite separators containing metal-organic-framework (MOF) particles and poly(vinyl alcohol) are fabricated by the electrospinning process. The MOF particles containing opened metal sites can spontaneously adsorb anions while allowing effective transport of lithium ions in the electrolyte, leading to dramatically improved lithium-ion transference number tLi + (up to 0.79) and lithium-ion conductivity. Meanwhile, the incorporation of the MOF particles alleviates the decomposition of the electrolyte, enhances the electrode reaction kinetics, and reduces the interface resistance between the electrolyte and the electrodes. Implementation of such composite separators in conventional lithium-ion batteries leads to significantly improved rate capability and cycling durability, offering a new prospective toward high-performance lithium-ion batteries.

18.
Adv Mater ; 31(19): e1805697, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30773720

RESUMO

As an essential component of immunotherapy, monoclonal antibodies (mAbs) have emerged as a class of powerful therapeutics for treatment of a broad range of diseases. For central nervous system (CNS) diseases, however, the efficacy remains limited due to their inability to enter the CNS. A platform technology is reported here that enables effective delivery of mAbs to the CNS for brain tumor therapy. This is achieved by encapsulating the mAbs within nanocapsules that contain choline and acetylcholine analogues; such analogues facilitate the penetration of the nanocapsules through the brain-blood barrier and the delivery of mAbs to tumor sites. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated.


Assuntos
Anticorpos Monoclonais/farmacocinética , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Nanocápsulas/química , Acetilcolina/metabolismo , Animais , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo , Colina/metabolismo , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Humanos , Imunoterapia/métodos , Masculino , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Permeabilidade , Fosforilcolina/química
19.
Adv Mater ; 31(18): e1807557, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803073

RESUMO

Central nervous system (CNS) diseases are the leading cause of morbidity and mortality; their treatment, however, remains constrained by the blood-brain barrier (BBB) that impedes the access of most therapeutics to the brain. A CNS delivery platform for protein therapeutics, which is achieved by encapsulating the proteins within nanocapsules that contain choline and acetylcholine analogues, is reported herein. Mediated by nicotinic acetylcholine receptors and choline transporters, such nanocapsules can effectively penetrate the BBB and deliver the therapeutics to the CNS, as demonstrated in mice and non-human primates. This universal platform, in general, enables the delivery of any protein therapeutics of interest to the brain, opening a new avenue for the treatment of CNS diseases.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Portadores de Fármacos/química , Proteínas/química , Animais , Barreira Hematoencefálica/metabolismo , Doenças do Sistema Nervoso Central/veterinária , Camundongos , Nanocápsulas/química , Fator de Crescimento Neural/química , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/uso terapêutico , Células PC12 , Polímeros/química , Primatas , Proteínas/metabolismo , Proteínas/uso terapêutico , Ratos , Rituximab/química , Rituximab/metabolismo , Rituximab/uso terapêutico
20.
Front Immunol ; 10: 3132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32047498

RESUMO

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.

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