Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles

Rodriguez, Pia L.; Harada, Takamasa; Christian, David A.; Pantano, Diego A.; Tsai, Richard K.; Discher, Dennis E.

doi:10.1126/science.1229568

Cited by 838 publications

(710 citation statements)

References 40 publications

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“…16 Interaction of CD47 with SIRPa negatively regulates phagocytosis of host cells by macrophages. [17][18][19][20][21] Consistently, anti-CD47 antibody or engineered SIRPa variants with increased affinity for CD47 can induce potent tumoricidal activity of macrophage by antagonizing CD47 on cancer cells. 22,23 In lungs, ligation of SIRPa to macrophages by surfactant proteins is required to keep the activity of alveolar macrophages in check, thus preventing damage to the airways caused by pro-inflamatory responses.…”

Section: Introductionmentioning

confidence: 94%

Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity

et al. 2016

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Despite their central function in tumor immunity, dendritic cells (DCs) can respond to inhibitory signals and become tolerogenic, curtailing T cell responses in vivo. Here, we provide the evidence for an inhibitory function of signal regulatory protein (SIRP) a in DC survival and activation. In tumors from human liver cancer patients, infiltrative DCs expressed elevated levels of SIRPa, which is correlated with the induction of immune tolerance within the tumors. Silencing of SIRPa resulted in a significant increase in the longevity of antigen-pulsed DCs in the draining lymph nodes. In addition, SIRPa controls the activation and output of DCs. Silencing of DC-expressed SIRPa induced spontaneous and enhanced production of IL12 and costimulatory molecules, resulting in more potent cytotoxic T lymphocyte responses, including the eradication of previously established solid tumors. SIRPa exerted such effects, at least in part, via the association and sequestration of p85 subunit of PI3K. Thus, SIRPa is a critical regulator of DC lifespan and activity, and its inhibition might improve the clinical efficacy of DC-based tumor vaccines.

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Section: Introductionmentioning

confidence: 94%

Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity

et al. 2016

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“…[159] As a consequence, surface modification of PLGA nanoparticles with CD47 market, considered as a "stealth or inert artificial structure," is indeed one of the most promising strategies to escape phagocyte uptake and consequently, early PLGA-based DDSs clearance. [160] Discher et al proved the successful attachment of CD47 "self" peptides to the surface of nanoparticles and the consequent increase in the circulation lifetime of the nanosystem, due to a delay in the phagocytic clearance by liver and spleen. [160] On the other hand, Liangfang Zhang research group developed fashion PLGA nanoparticles with lipidic and protein membranes isolated from RBCs as a biomimetic camouflaged delivery system.…”

Section: Functionalized Poly(lactic-co-glycolic) Acid-based Drug Delimentioning

confidence: 99%

“…[160] Discher et al proved the successful attachment of CD47 "self" peptides to the surface of nanoparticles and the consequent increase in the circulation lifetime of the nanosystem, due to a delay in the phagocytic clearance by liver and spleen. [160] On the other hand, Liangfang Zhang research group developed fashion PLGA nanoparticles with lipidic and protein membranes isolated from RBCs as a biomimetic camouflaged delivery system. [161] The elimination half-time for RBC-membrane-coated nanoparticles (RBC-NPs) and PEGcoated nanoparticles was calculated based on two-compartment model after their in vivo administration.…”

Section: Functionalized Poly(lactic-co-glycolic) Acid-based Drug Delimentioning

confidence: 99%

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

Martins

Sousa

Araújo

et al. 2017

Adv Healthcare Materials

201

133

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Poly(lactic‐co‐glycolic) acid (PLGA) is one of the most versatile biomedical polymers, already approved by regulatory authorities to be used in human research and clinics. Due to its valuable characteristics, PLGA can be tailored to acquire desirable features for control bioactive payload or scaffold matrix. Moreover, its chemical modification with other polymers or bioconjugation with molecules may render PLGA with functional properties that make it the Holy Grail among the synthetic polymers to be applied in the biomedical field. In this review, the physical–chemical properties of PLGA, its synthesis, degradation, and conjugation with other polymers or molecules are revised in detail, as well as its applications in drug delivery and regeneration fields. A particular focus is given to successful examples of products already on the market or at the late stages of trials, reinforcing the potential of this polymer in the biomedical field.

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“…Understanding how particle properties affect cell uptake is not only critical for designing improved therapeutic and diagnostic agents (1, 2) but also essential for efficient in vitro cell manipulation (3) and evaluating nanomaterial toxicity (4). Nanoparticle uptake by cells has been shown to depend on particle size, surface charge, and material compositions (5)(6)(7). Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms

Agarwal¹,

Singh

Jurney

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

368

336

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Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell type-specific. Although macropinocytosis is used by both epithelial and endothelial cells, epithelial cells uniquely internalize these nanoparticles using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on the other hand, use clathrin-mediated uptake for all shapes and show significantly higher uptake efficiency compared with epithelial cells. Using results from both upright and inverted cultures, we propose that nanoparticle internalization is a complex manifestation of three shape-and size-dependent parameters: particle surface-to-cell membrane contact area, i.e., particle-cell adhesion, strain energy for membrane deformation, and sedimentation or local particle concentration at the cell membrane. These studies provide a fundamental understanding on how nanoparticle uptake in different mammalian cells is influenced by the nanoscale geometry and is critical for designing improved nanocarriers and predicting nanomaterial toxicity.cell-uptake mechanism | nanoimprint lithography | drug delivery P olymeric nanoparticles are widely studied for delivering therapeutic and imaging payloads to cells. Understanding how particle properties affect cell uptake is not only critical for designing improved therapeutic and diagnostic agents (1, 2) but also essential for efficient in vitro cell manipulation (3) and evaluating nanomaterial toxicity (4). Nanoparticle uptake by cells has been shown to depend on particle size, surface charge, and material compositions (5-7). Recent advances in fabrication technologies have enabled generation of shape-specific microparticles and nanoparticles (8-12). These particles, inspired by the diverse, evolutionarily conserved shapes of pathogens and cells, are being used to study the role of carrier shape on cellular internalization, in vivo transport, and organ distribution (6,11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).Despite these pioneering studies, there remains a significant knowledge gap in our fundamental understanding of the interplay between nanoscale shape and size on cellular internalization, especially for clinically relevant polymer-based hydrophilic nanoparticles. Most in vivo drug delivery and imaging applicati...

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Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles

Cited by 838 publications

References 40 publications

Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity

Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms

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