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Weiwei Gao

Bio: Weiwei Gao is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Graphene & Medicine. The author has an hindex of 69, co-authored 205 publications receiving 14280 citations. Previous affiliations of Weiwei Gao include Harvard University & University of California.


Papers
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Journal ArticleDOI
01 Oct 2015-Nature
TL;DR: The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.
Abstract: Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.

1,155 citations

Journal ArticleDOI
TL;DR: The biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells is reported on, showing that by coupling the particles with an immunological adjuvant, the resulting formulation can be used to promote a tumor-specific immune response for use in vaccine applications.
Abstract: Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells This top-down engineering approach c

995 citations

Journal ArticleDOI
TL;DR: There is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this developing technology, cell‐membrane‐coating nanotechnology.
Abstract: Nanoparticle-based therapeutic, prevention, and detection modalities have the potential to greatly impact how diseases are diagnosed and managed in the clinic. With the wide range of nanomaterials available, the rational design of nanocarriers on an application-specific basis has become increasingly commonplace. Here, a comprehensive overview is provided on an emerging platform: cell-membrane-coating nanotechnology. As a fundamental unit of biology, cells carry out a wide range of functions, including the remarkable ability to interface and interact with their surrounding environment. Instead of attempting to replicate such functions via synthetic techniques, researchers are now directly leveraging naturally derived cell membranes as a means of bestowing nanoparticles with enhanced biointerfacing capabilities. This top-down technique is facile, highly generalizable, and has the potential to greatly augment existing nanocarriers. Further, the introduction of a natural membrane substrate onto nanoparticles surfaces has enabled additional applications beyond those traditionally associated with nanomedicine. Despite its relative youth, there exists an impressive body of literature on cell membrane coating, which is covered here in detail. Overall, there is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this developing technology.

908 citations

Journal ArticleDOI
TL;DR: The novel developments described here may revise the classical outlook that NPs are passive delivery vehicles, in favor of responsive, sensing vehicles that use environmental cues to achieve maximal drug potency.
Abstract: First-generation nanoparticles (NPs) have been clinically translated as pharmaceutical drug delivery carriers for their ability to improve on drug tolerability, circulation half-life, and efficacy. Toward the development of the next-generation NPs, researchers have designed novel multifunctional platforms for sustained release, molecular targeting, and environmental responsiveness. This review focuses on environmentally responsive mechanisms used in NP designs, and highlights the use of pH-responsive NPs in drug delivery. Different organs, tissues, and subcellular compartments, as well as their pathophysiological states, can be characterized by their pH levels and gradients. When exposed to these pH stimuli, pH-responsive NPs respond with physicochemical changes to their material structure and surface characteristics. These include swelling, dissociating or surface charge switching, in a manner that favors drug release at the target site over surrounding tissues. The novel developments described here may ...

793 citations

Journal ArticleDOI
TL;DR: A nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management that can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage is shown.
Abstract: Rheumatoid arthritis is a common chronic inflammatory disorder and a major cause of disability. Despite the progress made with recent clinical use of anti-cytokine biologics, the response rate of rheumatoid arthritis treatment remains unsatisfactory, owing largely to the complexity of cytokine interactions and the multiplicity of cytokine targets. Here, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management. By fusing neutrophil membrane onto polymeric cores, we prepare neutrophil membrane-coated nanoparticles that inherit the antigenic exterior and associated membrane functions of the source cells, which makes them ideal decoys of neutrophil-targeted biological molecules. It is shown that these nanoparticles can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage. In a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, the neutrophil membrane-coated nanoparticles show significant therapeutic efficacy by ameliorating joint damage and suppressing overall arthritis severity.

506 citations


Cited by
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01 May 1993
TL;DR: Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems.
Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

29,323 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: Novel engineering approaches are discussed that capitalize on the growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.
Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

3,800 citations

Journal ArticleDOI
TL;DR: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘ how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?'
Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

3,335 citations