Professional Education


  • Doctor of Philosophy, University of California Los Angeles (2019)
  • B.S., Jilin University, Chemistry & Biotechnology (2012)
  • M.A., Washington University in St. Louis, Chemistry (2014)

Stanford Advisors


All Publications


  • Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates FRONTIERS IN IMMUNOLOGY Qin, M., Wang, L., Wu, D., Williams, C. K., Xu, D., Kranz, E., Guo, Q., Guan, J., Vinters, H. V., Lee, Y., Xie, Y., Luo, Y., Sun, G., Sun, X., He, Z., Lu, Y., Kamata, M., Wen, J., Chen, I. Y. 2020; 10: 3132

    Abstract

    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.

    View details for DOI 10.3389/fimmu.2019.03132

    View details for Web of Science ID 000513689600001

    View details for PubMedID 32047498

    View details for PubMedCentralID PMC6996053

  • Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice NATURE BIOMEDICAL ENGINEERING Wen, J., Wu, D., Qin, M., Liu, C., Wang, L., Xu, D., Vinters, H. V., Liu, Y., Kranz, E., Guan, X., Sun, G., Sun, X., Lee, Y., Martinez-Maza, O., Widney, D., Lu, Y., Chen, I. Y., Kamata, M. 2019; 3 (9): 706–16

    Abstract

    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.

    View details for DOI 10.1038/s41551-019-0434-z

    View details for Web of Science ID 000485111600009

    View details for PubMedID 31384008

    View details for PubMedCentralID PMC6736720

  • Real-Time Quantification of Cell Internalization Kinetics by Functionalized Bioluminescent Nanoprobes. Advanced materials (Deerfield Beach, Fla.) Wu, D., Yang, Y., Xu, P., Xu, D., Liu, Y., Castillo, R., Yan, R., Ren, J., Zhou, G., Liu, C., Qin, M., Du, J., Hou, L., Chen, I., Kang, C., Jin, L., Wen, J., Chen, W., Lu, Y. 2019: e1902469

    Abstract

    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.

    View details for DOI 10.1002/adma.201902469

    View details for PubMedID 31402525

  • Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration. Advanced materials (Deerfield Beach, Fla.) Xu, D., Wu, D., Qin, M., Nih, L. R., Liu, C., Cao, Z., Ren, J., Chen, X., He, Z., Yu, W., Guan, J., Duan, S., Liu, F., Liu, X., Li, J., Harley, D., Xu, B., Hou, L., Chen, I. S., Wen, J., Chen, W., Pourtaheri, S., Lu, Y. 2019: e1900727

    Abstract

    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.

    View details for DOI 10.1002/adma.201900727

    View details for PubMedID 31125138

  • A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System. Advanced materials (Deerfield Beach, Fla.) Wu, D., Qin, M., Xu, D., Wang, L., Liu, C., Ren, J., Zhou, G., Chen, C., Yang, F., Li, Y., Zhao, Y., Huang, R., Pourtaheri, S., Kang, C., Kamata, M., Chen, I. S., He, Z., Wen, J., Chen, W., Lu, Y. 2019: e1807557

    Abstract

    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.

    View details for PubMedID 30803073

  • Systemic Delivery of Monoclonal Antibodies to the Central Nervous System for Brain Tumor Therapy. Advanced materials (Deerfield Beach, Fla.) Han, L., Liu, C., Qi, H., Zhou, J., Wen, J., Wu, D., Xu, D., Qin, M., Ren, J., Wang, Q., Long, L., Liu, Y., Chen, I., Yuan, X., Lu, Y., Kang, C. 2019: e1805697

    Abstract

    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.

    View details for PubMedID 30773720

  • Nanocapsules of oxalate oxidase for hyperoxaluria treatment NANO RESEARCH Zhao, M., Xu, D., Wu, D., Whittaker, J. W., Terkeltaub, R., Lu, Y. 2018; 11 (5): 2682–88
  • Fabrication of Hybrid Silicate Coatings by a Simple Vapor Deposition Method for Lithium Metal Anodes ADVANCED ENERGY MATERIALS Liu, F., Xiao, Q., Wu, H., Shen, L., Xu, D., Cai, M., Lu, Y. 2018; 8 (6)
  • A Hepatocyte-Mimicking Antidote for Alcohol Intoxication. Advanced materials (Deerfield Beach, Fla.) Xu, D., Han, H., He, Y., Lee, H., Wu, D., Liu, F., Liu, X., Liu, Y., Lu, Y., Ji, C. 2018; 30 (22): e1707443

    Abstract

    Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to remove alcohol efficiently. Upon alcohol consumption, alcohol is sequentially oxidized to acetaldehyde and acetate by the endogenous alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Inspired by the metabolism of alcohol, a hepatocyte-mimicking antidote for alcohol intoxication through the codelivery of the nanocapsules of alcohol oxidase (AOx), catalase (CAT), and aldehyde dehydrogenase (ALDH) to the liver, where AOx and CAT catalyze the oxidation of alcohol to acetaldehyde, while ALDH catalyzes the oxidation of acetaldehyde to acetate. Administered to alcohol-intoxicated mice, the antidote rapidly accumulates in the liver and enables a significant reduction of the blood alcohol concentration. Moreover, blood acetaldehyde concentration is maintained at an extremely low level, significantly contributing to liver protection. Such an antidote, which can eliminate alcohol and acetaldehyde simultaneously, holds great promise for the treatment of alcohol intoxication and poisoning and can provide therapeutic benefits.

    View details for PubMedID 29638019

    View details for PubMedCentralID PMC6386471

  • Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management. Journal of controlled release : official journal of the Controlled Release Society Zhang, X., Xu, D., Jin, X., Liu, G., Liang, S., Wang, H., Chen, W., Zhu, X., Lu, Y. 2017; 255: 54–61

    Abstract

    Among a broad spectrum of medical treatments, protein therapeutics holds tremendous opportunities for the treatment of metabolic disorders, cancer, autoimmune diseases and etc. Broad adaption of protein therapeutics, however, still remain challenging, not only because of poor protein stability, but they also experience fast clearance after administrated and elicit immune responses, resulting in undesirable biodistribution and short blood residence time. In this study, we demonstrate a novel protein delivery method via encapsulating therapeutic proteins within thin shells of poly(N-vinylpyrrolidone) (PVP), which leads to significantly improved protein stability, reduced macrophage uptake, prolonged circulation time and reduced immunogenicity. Exemplified with urate oxidase (UOx), the enzyme used for hyperuricemia treatment, as-formed UOx nanocapsules, n(UOx), exhibits enhanced stability, more significant therapeutic effects, and a more than 10-fold improvement in circulation time when compared with native UOx. This technology not only demonstrates the use of UOx nanocapsules for hyperuricemia management, but also provides a general approach for a broad spectrum of therapeutic proteins for in vivo applications.

    View details for PubMedID 28288895

  • Prolonging the plasma circulation of proteins by nano-encapsulation with phosphorylcholine-based polymer NANO RESEARCH Zhang, L., Liu, Y., Liu, G., Xu, D., Liang, S., Zhu, X., Lu, Y., Wang, H. 2016; 9 (8): 2424–32
  • An intracellular protein delivery platform based on glutathione-responsive protein nanocapsules. Chemical communications (Cambridge, England) Li, J., Zhang, L., Liu, Y., Wen, J., Wu, D., Xu, D., Segura, T., Jin, J., Lu, Y., Wang, H. 2016; 52 (93): 13608–11

    Abstract

    An efficient strategy for the intracellular delivery of proteins was developed based on assembling proteins with a self-crosslinkable polymer. Such a disulfide-crosslinking structure enhances the stability of the protein-polymer assembly, and also allows effective dissociation of the assembly in response to glutathione, which allows effective delivery of various proteins with high intracellular bioactivity.

    View details for PubMedID 27808287

  • Structural insight into the type-II mitochondrial NADH dehydrogenases NATURE Feng, Y., Li, W., Li, J., Wang, J., Ge, J., Xu, D., Liu, Y., Wu, K., Zeng, Q., Wu, J., Tian, C., Zhou, B., Yang, M. 2012; 491 (7424): 478-+

    Abstract

    The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.

    View details for DOI 10.1038/nature11541

    View details for Web of Science ID 000311031600053

    View details for PubMedID 23086143