The role of substrate topography on the cellular uptake of nanoparticles

Huang, Changjin; Özdemir, Tuğba; Xu, Li Chong; Butler, Peter E. M.; Siedlecki, Christopher A.; Brown, Justin L.; Zhang, Sulin

doi:10.1002/jbm.b.33397

Cited by 36 publications

(33 citation statements)

References 58 publications

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“…By mediating cell spreading and cytoplasm membrane tension, nanotopography modulates nuclear deformation and thus alters cell proliferation and nuclear accessibility to nonviral vectors. 44,45 Nanotopography-mediated cell spreading also affects cell contractility and then type I collagen production. 46 …”

Section: Resultsmentioning

confidence: 99%

Nanotopographical Modulation of Cell Function through Nuclear Deformation

Wang

Bruce

Mezan

et al. 2016

ACS Appl. Mater. Interfaces

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Although nanotopography has been shown to be a potent modulator of cell behavior, it is unclear how the nanotopographical cue, through focal adhesions, affects the nucleus, eventually influencing cell phenotype and function. Thus, current methods to apply nanotopography to regulate cell behavior are basically empirical. We, herein, engineered nanotopographies of various shapes (gratings and pillars) and dimensions (feature size, spacing and height), and thoroughly investigated cell spreading, focal adhesion organization and nuclear deformation of human primary fibroblasts as the model cell grown on the nanotopographies. We examined the correlation between nuclear deformation and cell functions such as cell proliferation, transfection and extracellular matrix protein type I collagen production. It was found that the nanoscale gratings and pillars could facilitate focal adhesion elongation by providing anchoring sites, and the nanogratings could orient focal adhesions and nuclei along the nanograting direction, depending on not only the feature size but also the spacing of the nanogratings. Compared with continuous nanogratings, discrete nanopillars tended to disrupt the formation and growth of focal adhesions and thus had less profound effects on nuclear deformation. Notably, nuclear volume could be effectively modulated by the height of nanotopography. Further, we demonstrated that cell proliferation, transfection, and type I collagen production were strongly associated with the nuclear volume, indicating that the nucleus serves as a critical mechanosensor for cell regulation. Our study delineated the relationships between focal adhesions, nucleus and cell function and highlighted that the nanotopography could regulate cell phenotype and function by modulating nuclear deformation. This study provides insight into the rational design of nanotopography for new biomaterials and the cell–substrate interfaces of implants and medical devices.

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Section: Resultsmentioning

confidence: 99%

Nanotopographical Modulation of Cell Function through Nuclear Deformation

Wang

Bruce

Mezan

et al. 2016

ACS Appl. Mater. Interfaces

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“…Using poly(methyl methacrylate) (PMMA) fibrous substrates fabricated via electrospinning, Huang et al 118 further explored the effects of substrate topography, characterized by the fibril density, on the cellular uptake of NPs. Substrates of three types of topographies, flat PMMA surface, and sparse and dense PMMA fibrous substrates, were used.…”

Section: Local Mechanical Environmental Effectsmentioning

confidence: 99%

Physical Principles of Nanoparticle Cellular Endocytosis

2015

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This review article focuses on the physiochemical mechanisms underlying nanoparticle uptake into cells. When nanoparticles are in close vicinity to a cell, the interactions between the nanoparticles and the cell membrane generate forces from different origins. This leads to the membrane wrapping of the nanoparticles followed by cellular uptake. This article discusses how the kinetics, energetics, and forces are related to these interactions and dependent on the size, shape, and stiffness of nanoparticles, the biomechanical properties of the cell membrane, as well as the local environment of the cells. The discussed fundamental principles of the physiochemical causes for nanoparticle–cell interaction may guide new studies of nanoparticle endocytosis and lead to better strategies to design nanoparticle-based approaches for biomedical applications.

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“…NPs can be also conjugated with monoclonal antibodies, a process preventing them from immunological system response [19]. Moreover, thanks to the possibility of modifying the physicochemical properties of NPs, a smooth endocytosis into the cancer cells can occur [20]. NPs have also found their application in nanodiagnostics as biosensors for an early stage tumor markers detection [21] and in gene therapy as carriers delivering into cancer cells foreign nucleic acids that encode proteins killing the tumor cells [22].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles of Titanium and Zinc Oxides as Novel Agents in Tumor Treatment: a Review

2017

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Cancer has become a global problem. On all continents, a great number of people are diagnosed with this disease. In spite of the progress in medical care, cancer still ends fatal for a great number of the ill, either as a result of a late diagnosis or due to inefficiency of therapies. The majority of the tumors are resistant to drugs. Thus, the search for new, more effective therapy methods continues. Recently, nanotechnology has been attributed with big expectations in respect of the cancer fight. That interdisciplinary field of science creates nanomaterials (NMs) and nanoparticles (NPs) that can be applied, e.g., in nanomedicine. NMs and NPs are perceived as very promising in cancer therapy since they can perform as drug carriers, as well as photo- or sonosensitizers (compounds that generate the formation of reactive oxygen species as a result of either electromagnetic radiation excitation with an adequate wavelength or ultrasound activation, respectively). Consequently, two new treatment modalities, the photodynamic therapy (PDT) and the sonodynamic therapy (SDT) have been created. The attachment of ligands or antibodies to NMs or to NPs improve their selective distribution into the targeted organ or cell; hence, the therapy effectiveness can be improved. An important advantage of the targeted tumor treatment is lowering the cyto- and genotoxicity of active substance towards healthy cells. Therefore, both PDT and SDT constitute a valuable alternative to chemo- or radiotherapy. The vital role in cancer eradication is attributed to two inorganic sensitizers in their nanosized scale: titanium dioxide and zinc oxide.

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The role of substrate topography on the cellular uptake of nanoparticles

Cited by 36 publications

References 58 publications

Nanotopographical Modulation of Cell Function through Nuclear Deformation

Nanotopographical Modulation of Cell Function through Nuclear Deformation

Physical Principles of Nanoparticle Cellular Endocytosis

Nanoparticles of Titanium and Zinc Oxides as Novel Agents in Tumor Treatment: a Review

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