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  • Wiley  (7)
  • Liu, Yang  (7)
  • Shi, Linqi  (7)
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  • Wiley  (7)
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  • 1
    Online Resource
    Online Resource
    Dual‐Locking Nanoparticles Disrupt the PD‐1/PD‐L1 Pathway for Efficient Cancer Immunotherapy
    Wiley ; 2019
    In:  Advanced Materials Vol. 31, No. 51 ( 2019-12)
    Details
    In: Advanced Materials, Wiley, Vol. 31, No. 51 ( 2019-12)
    Abstract: The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated (Cas) enzyme, Cas13a, holds great promise in cancer treatment due to its potential for selective destruction of tumor cells via collateral effects after target recognition. However, these collateral effects do not specifically target tumor cells and may cause safety issues when administered systemically. Herein, a dual‐locking nanoparticle (DLNP) that can restrict CRISPR/Cas13a activation to tumor tissues is described. DLNP has a core–shell structure, in which the CRISPR/Cas13a system (plasmid DNA, pDNA) is encapsulated inside the core with a dual‐responsive polymer layer. This polymer layer endows the DLNP with enhanced stability during blood circulation or in normal tissues and facilitates cellular internalization of the CRISPR/Cas13a system and activation of gene editing upon entry into tumor tissue. After carefully screening and optimizing the CRISPR RNA (crRNA) sequence that targets programmed death‐ligand 1 (PD‐L1), DLNP demonstrates the effective activation of T‐cell‐mediated antitumor immunity and the reshaping of immunosuppressive tumor microenvironment (TME) in B16F10‐bearing mice, resulting in significantly enhanced antitumor effect and improved survival rate. Further development by replacing the specific crRNA of target genes can potentially make DLNP a universal platform for the rapid development of safe and efficient cancer immunotherapies.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    URL: Article
    DOI: 10.1002/adma.v31.51
    DOI: 10.1002/adma.201905751
    RVK:
    UA 1538
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1474949-X
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  • 2
    Online Resource
    Online Resource
    In Situ Modification of the Tumor Cell Surface with Immunomodulating Nanoparticles for Effective Suppression of Tumor Growth in Mice
    Wiley ; 2019
    In:  Advanced Materials Vol. 31, No. 32 ( 2019-08)
    Details
    In: Advanced Materials, Wiley, Vol. 31, No. 32 ( 2019-08)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    URL: Article
    DOI: 10.1002/adma.v31.32
    DOI: 10.1002/adma.201902542
    RVK:
    UA 1538
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1474949-X
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  • 3
    Online Resource
    Online Resource
    Liquid Core Nanoparticle with High Deformability Enables Efficient Penetration across Biological Barriers
    Wiley ; 2023
    In:  Advanced Healthcare Materials Vol. 12, No. 5 ( 2023-02)
    Details
    In: Advanced Healthcare Materials, Wiley, Vol. 12, No. 5 ( 2023-02)
    Abstract: Biological barriers significantly limit the delivery efficiency of drug delivery systems, resulting in undesired therapeutic effects. When designing a delivery system with optimized penetration behavior across the biological barriers, mechanical properties, such as deformability, are emerging as important parameters that need to be considered, although they are usually neglected in current research. Herein, a liquid core nanoparticle (LCN) composed of a polymer‐encapsulated edible oil droplet is demonstrated. Owing to the unique structure in which the liquid oil core is encapsulated by a layer of highly hydrophilic and cross‐linked polymer, the LCN exhibits high mechanical softness, making it deformable under external forces. With high deformability, LCNs can effectively penetrate through several important biological barriers including deep tumor tissue, blood–brain barriers, mucus layers, and bacterial biofilms. Moreover, the potential of the LCN as a drug delivery system is also demonstrated by the loading and release of several clinical drugs. With the capability of penetrating biological barriers and delivering drugs, LCN provides a potential platform for disease treatments, particularly for those suffering from inadequate drug penetration.
    Type of Medium: Online Resource
    ISSN: 2192-2640 , 2192-2659
    URL: Issue
    URL: Article
    DOI: 10.1002/adhm.v12.5
    DOI: 10.1002/adhm.202201889
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2645585-7
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  • 4
    Online Resource
    Online Resource
    Multistage Delivery Nanoparticle Facilitates Efficient CRISPR/dCas9 Activation and Tumor Growth Suppression In Vivo
    Wiley ; 2019
    In:  Advanced Science Vol. 6, No. 1 ( 2019-01)
    Details
    In: Advanced Science, Wiley, Vol. 6, No. 1 ( 2019-01)
    Abstract: CRISPR/dCas9 systems can precisely control endogenous gene expression without interrupting host genomic sequence and have provided a novel and feasible strategy for the treatment of cancers at the transcriptional level. However, development of CRISPR/dCas9‐based anti‐cancer therapeutics remains challenging due to the conflicting requirements for the design of the delivery system: a cationic and membrane‐binding surface facilitates the tumor accumulation and cellular uptake of the CRISPR/dCas9 system, but hinders the circulating stability in vivo. Here, a multistage delivery nanoparticle (MDNP) that can achieve tumor‐targeted delivery of CRISPR/dCas9 systems and restore endogenous microRNA (miRNA) expression in vivo is described. MDNP is designed as a core‐shell structure in which the shell is made of a responsive polymer that endows MDNP with the capability to present different surface properties in response to its surrounding microenvironment, allowing the MNDP overcoming multiple physiological barriers and delivering the payload to tumor tissues with an optimal efficiency. Systemic administration of MDNP/dCas9‐miR‐524 to tumor‐bearing mice achieved effective upregulation of miR‐524 in tumors, leading to the simultaneous interferences of multiple signal pathways related to cancer cell proliferation and presenting remarkable tumor growth retardation, suggesting the feasibility of utilizing MDNP to achieve tumor‐targeting delivery of CRISPR/dCas9 with sufficient levels to realize its therapeutic effects.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v6.1
    DOI: 10.1002/advs.201801423
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2808093-2
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  • 5
    Online Resource
    Online Resource
    Spatial Distribution Control of Antimicrobial Peptides through a Novel Polymeric Carrier for Safe and Efficient Cancer Treatment
    Wiley ; 2022
    In:  Advanced Materials Vol. 34, No. 23 ( 2022-06)
    Details
    In: Advanced Materials, Wiley, Vol. 34, No. 23 ( 2022-06)
    Abstract: Antimicrobial peptides (AMPs) hold great potential for use in tumor treatment. However, developing AMP‐based antitumor therapies is challenging due to circulatory instability, hemolytic toxicity, low selectivity, and poor cell permeability of AMPs. In this study, a polymeric carrier for AMPs (denoted as PAMP m ‐ co ‐PPBE n /PCA) is presented that effectively enhances their anticancer efficacy while minimizing their potential side effects. By integrating multiple responsive structures at the molecular level, the carrier finely controls the spatial distribution of AMPs in different biological microenvironments, thereby effectively modulating their membranolytic ability. Upon employing KLA as the model AMP, the polymeric carrier's hemolytic toxicity during blood circulation is suppressed, its cellular internalization when reaching tumor tissues facilitated, and its membranolytic toxicity toward the mitochondria upon entering cancer cells restored and further enhanced. Animal studies indicate that this approach significantly improves the antitumor efficacy of KLA and reduces its toxicity. Considering that the loading method for most AMPs is identical to that of KLA, the polymeric carrier reported in this study may provide a feasible approach for the development of AMP‐based cancer treatments.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    URL: Article
    DOI: 10.1002/adma.v34.23
    DOI: 10.1002/adma.202201945
    RVK:
    UA 1538
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1474949-X
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  • 6
    Online Resource
    Online Resource
    Arginine‐Rich Polymers with Pore‐Forming Capability Enable Efficient Intracellular Delivery via Direct Translocation Across Cell Membrane
    Wiley ; 2022
    In:  Advanced Healthcare Materials Vol. 11, No. 14 ( 2022-07)
    Details
    In: Advanced Healthcare Materials, Wiley, Vol. 11, No. 14 ( 2022-07)
    Abstract: Efficient delivery of biomacromolecules or drugs across the cell membrane via endocytosis usually encounters inevitable entrapment in endosomes and subsequent degradation in lyso‐endosomes. To address this issue, a series of arginine‐rich cell penetrating polymers is designed and synthesized, which internalize into cells by inducing the formation of pores on the cell membrane, thereby crossing the cell membrane via direct translocation that fundamentally avoids endo/lysosomal entrapment. The structure−activity relationship studies show that PTn‐R2‐C6, which is a type of polymer that has two arginine residues and a flexible hexanoic acid linker in each side chain, exhibits excellent pore‐formation ability on the cell membrane. Further investigations indicate that PTn‐R2‐C6 rapidly transports plasmid DNAs into cytosol through a similar endocytosis‐independent pathway, thereby achieving significantly higher transfection efficiency and lower cytotoxicity than the gold‐standard transfection reagent PEI 25K. These results suggest the great potential of PTn‐R2‐C6 as a safe and efficient gene transfection reagent for wide applications including disease treatments, vaccine development, and biomedical research purposes.
    Type of Medium: Online Resource
    ISSN: 2192-2640 , 2192-2659
    URL: Issue
    URL: Article
    DOI: 10.1002/adhm.v11.14
    DOI: 10.1002/adhm.202200371
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2645585-7
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  • 7
    Online Resource
    Online Resource
    Calixarene‐Embedded Nanoparticles for Interference‐Free Gene–Drug Combination Cancer Therapy
    Wiley ; 2021
    In:  Small Vol. 17, No. 8 ( 2021-02)
    Details
    In: Small, Wiley, Vol. 17, No. 8 ( 2021-02)
    Abstract: Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene‐embedded nanoparticle (CENP) is developed to co‐deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference‐free gene–drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid‐responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia‐responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host–guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA‐based CRISPR interference system that targets miR‐21, CENP exhibits the significantly enhanced anti‐tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference‐free gene–drug combination cancer therapy.
    Type of Medium: Online Resource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    URL: Article
    DOI: 10.1002/smll.v17.8
    DOI: 10.1002/smll.202006223
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2168935-0
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