Cell Surface Self-Assembly of Hybrid Nanoconjugates <i>via</i> Oligonucleotide Hybridization Induces Apoptosis

Chu, Te Wei; Yang, Jiyuan; Zhang, Rui; Sima, Monika; Kopeček, Jindřich

doi:10.1021/nn4053827

Cited by 77 publications

(154 citation statements)

References 59 publications

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“…Increasing the valency of a conjugate has been shown to increase effectiveness in the context of plasma membrane receptors and multivalent ligands. [25] Given the complexity of the experiments, we limited ourselves to a polymer carrying (on average) three peptides per backbone. We hypothesized that this number is sufficient for promoting interactions.…”

Section: Resultsmentioning

confidence: 99%

A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction

et al. 2015

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In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline-rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N-(2-hydroxypropyl)methacrylamide polymer backbone. When added to GADS-containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross-linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins.

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Section: Resultsmentioning

confidence: 99%

A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction

et al. 2015

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“…Further addition of copolymer grafted with multiple copies of MORF2 resulted in MORF1 and MORF2 hybridization at the cell surface with concomitant CD20 cross-linking, which triggered cell apoptosis, resulting in improved long term survival in a murine model of human nonHodgkin's lymphoma. 117 Although CD20 mAbs (e.g., obinutuzumab) can also induce direct apoptosis, this approach could also potentially reduce adverse effects.…”

Section: Hybrid Npsmentioning

confidence: 99%

Potential applications of nanoparticles in cancer immunotherapy

Jia

Omri

Krishnan

et al. 2016

Human Vaccines & Immunotherapeutics

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In recent years considerable progress has been made in the field of cancer immunotherapy whereby treatments that modulate the body's own immune system are used to combat cancer. This has the potential to not only elicit strong anti-cancer immune responses which can break pre-existing tolerance and help promote tumor regression, but could also induce immunological memory which may help prevent tumor recurrence. In order to ensure effective delivery of immunotherapeutic agents, such as vaccines, checkpoint inhibitors, chemotherapeutic agents and nucleic acids, a safe and effective delivery system is often required. One such approach is the use of multifunctional nanoparticles (NPs), such as liposomes, polymers, micelles, dendrimers, inorganic NPs, and hybrid NPs, which have the potential to combine the delivery of a diverse range of therapeutic immunomodulators thereby increasing the efficacy of tumor cell killing. This review focuses on recent progress in NP-mediated immunotherapy for the treatment of cancer.

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“…Sequential intravenous injections of Fab′-CCE and HPMA-CCK n led to extension of the survival period or increase in survival rate in SCID mice bearing human B-lymphoma xenografts (87). As an alternative to peptide pairs, which were found immunogenic in immunocompetent Balb/c mice (88), a complementary pair of morpholino oligonucleotides is currently pursued to improve binding kinetics and efficiency (89,90). The HPMA-based drug-free macromolecular therapeutics shows an example of new roles that the polymers can play beyond their traditional functions as a drug carrier.…”

Section: N-(2-hydroxypropyl) Mathacrylamide Copolymer Assemliesmentioning

confidence: 99%

Drug Carriers: Not an Innocent Delivery Man

Yeo

Kim

2015

AAPS J

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Abstract. Biomaterials used as drug carriers are often considered inactive and assumed to have no other roles than modifying pharmacokinetics and biodistribution of a drug. On the other hand, there are several examples in which the carrier materials show bioactivities in the body, which may have been underestimated or inadvertently ignored. This review highlights several examples where biomaterials used as drug carriers bring biological effects, known or newly discovered, and discusses their implications in development of new drug delivery systems.

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Cell Surface Self-Assembly of Hybrid Nanoconjugates via Oligonucleotide Hybridization Induces Apoptosis

Cited by 77 publications

References 59 publications

A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction

A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction

Potential applications of nanoparticles in cancer immunotherapy

Drug Carriers: Not an Innocent Delivery Man

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