Shape Induced Inhibition of Phagocytosis of Polymer Particles

Champion, Julie A.; Mitragotri, Samir

doi:10.1007/s11095-008-9626-z

Cited by 553 publications

(449 citation statements)

References 10 publications

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“…The engulfment of cylindrical parƟcles was observed to take place from the ends without excepƟon (Fig. 1), supporƟng the paradigm that phagocytosis is highly orientaƟon and shape dependent [1,2,4]. This means that the geometry at the point of first contact between the macrophage and the parƟcle governs the iniƟaƟon of phagocytosis.…”

Section: Resultsmentioning

confidence: 94%

“…This shapeinduced delay of internalizaƟon extends the residence Ɵme of the carrier system, represenƟng a new design parameter for the retardaƟon of clearance [4]. The nature of the used parƟcles dictates the condiƟons of release, either within the phagocyte or before internalizaƟon.…”

Section: Resultsmentioning

confidence: 99%

“…As a consequence, non-spherical parƟcles such as cylindrical parƟcles have the potenƟal to control clearance processes, a core prerequisite for a sustained release system for therapeuƟcs [2,4].…”

Section: Introducɵonmentioning

confidence: 99%

See 2 more Smart Citations

Macrophage uptake of cylindrical microparticles investigated with correlative microscopy

Tscheka

Hittinger

Lehr

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

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Macrophage uptake of cylindrical microparticles investigated with correlative microscopy

Tscheka

Hittinger

Lehr

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…Macrophages, an essential component of the immune system, play a major role in governing the fate of polymeric particles administered into the body for drug delivery or diagnostic applications (23)(24)(25). It has been shown that particles with high AR, such as EDs, have the potential to mitigate phagocytosis (26). We hypothesized that the ability of particles to switch shapes may be used to achieve precise control over the extent and duration of mitigation of phagocytosis.…”

Section: Resultsmentioning

confidence: 99%

“…Studies have demonstrated that departure from the conventional spherical shape of particles brings unique and improved functionalities to the particulate systems, resulting in improved biological responses. For example, macrophage-mediated phagocytosis is governed by the local geometry of the particles (40), and elongated particles exhibit reduced phagocytosis, longer circulation in the blood, and higher accumulation in target tissues (26,32,34,41). The same shape, however, impedes particle internalization into target cells compared to spheres (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Polymer particles that switch shape in response to a stimulus

Yoo

Mitragotri²

2010

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

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237

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Particle engineering for biomedical applications has unfolded the roles of attributes such as size, surface chemistry, and shape for modulating particle interactions with cells. Recently, dynamic manipulation of such key properties has gained attention in view of the need to precisely control particle interaction with cells. With increasing recognition of the pivotal role of particle shape in determining their biomedical applications, we report on polymeric particles that are able to switch their shape in real time in a stimulusresponsive manner. The shape-switching behavior was driven by a subtle balance between polymer viscosity and interfacial tension. The balance between the two forces was modulated by application of an external stimulus chosen from temperature, pH, or chemical additives. The dynamics of shape switch was precisely controlled over minutes to days under physiological conditions. Shapeswitching particles exhibited unique interactions with cells. Elliptical disk-shaped particles that are not phagocytosed by macrophages were made to internalize through shape switch, demonstrating the ability of shape-switchable particles in modulating interaction with cells.drug delivery | carrier | geometry | nanotechnology | phagocytosis I nteractions of polymeric particles with various cells, including macrophages, in the form of endocytosis and phagocytosis determine the effectiveness of carriers used for drug delivery and medical imaging (1, 2). The outcome of these interactions relies on optimal selection of key particle properties including surface chemistry, size, and shape (3, 4). Accordingly, numerous studies have reported on methods to synthesize materials with precisely engineered functional attributes such as size, surface chemistry, mechanical properties, and shape to facilitate or mitigate interactions with various cell types (3-5).For a given application, particle properties are optimized through extensive experimentation, and a set of fixed values are then chosen for further development. In reality, however, the optimal values of parameters may vary with time depending on the application. This variation has motivated the need to gain dynamic control over key particle properties so as to achieve an interactive interface between the particles and the complex biological milieu. For example, studies have reported on stimulusresponsive type control over the size of particles, and such particles have been used for the triggered release of encapsulated drugs (6-8). In another study, the surface chemistry of polymeric micelles has been controlled by using the environmental pH of solid tumors so as to enhance the cellular uptake and release of anticancer agents (9). Studies have also reported on achieving dynamic control of surface properties through the use of electric fields (10). Relatively little attention, however, has been devoted to switching particle's shape.Here we report poly(lactide-co-glycolide) (PLGA) particles whose shape can be switched in real time from an elliptical disk to a sphere in re...

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