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Abstract Nanoparticles have drawn intense interest as delivery agents for diagnosing and treating various cancers. Much of the early success was driven by passive targeting mechanisms such as the enhanced permeability and retention (EPR) effect, but this has failed to lead to the expected clinical successes. Active targeting involves binding interactions between the nanoparticle and cancer cells, which promotes tumor cell-specific accumulation and internalization. Furthermore, nanoparticles are large enough to facilitate multiple bond formation, which can improve adhesive properties substantially in comparison to the single bond case. While multivalent binding is universally believed to be an attribute of nanoparticles, it is a complex process that is still poorly understood and difficult to control. In this review, we will first discuss experimental studies that have elucidated roles for parameters such as nanoparticle size and shape, targeting ligand and target receptor densities, and monovalent binding kinetics on multivalent nanoparticle adhesion efficiency and cellular internalization. Although such experimental studies are very insightful, information is limited and confounded by numerous differences across experimental systems. Thus, we focus the second part of the review on theoretical aspects of binding, including kinetics, biomechanics, and transport physics. Finally, we discuss various computational and simulation studies of nanoparticle adhesion, including advanced treatments that compare directly to experimental results. Future work will ideally continue to combine experimental data and advanced computational studies to extend our knowledge of multivalent adhesion, as well as design the most powerful nanoparticle-based agents to treat cancer.
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Symmetry-breaking in patch formation on triangular gold nanoparticles by asymmetric polymer grafting
Abstract Synthesizing patchy particles with predictive control over patch size, shape, placement and number has been highly sought-after for nanoparticle assembly research, but is fraught with challenges. Here we show that polymers can be designed to selectively adsorb onto nanoparticle surfaces already partially coated by other chains to drive the formation of patchy nanoparticles with broken symmetry. In our model system of triangular gold nanoparticles and polystyrene- b -polyacrylic acid patch, single- and double-patch nanoparticles are produced at high yield. These asymmetric single-patch nanoparticles are shown to assemble into self-limited patch‒patch connected bowties exhibiting intriguing plasmonic properties. To unveil the mechanism of symmetry-breaking patch formation, we develop a theory that accurately predicts our experimental observations at all scales—from patch patterning on nanoparticles, to the size/shape of the patches, to the particle assemblies driven by patch‒patch interactions. Both the experimental strategy and theoretical prediction extend to nanoparticles of other shapes such as octahedra and bipyramids. Our work provides an approach to leverage polymer interactions with nanoscale curved surfaces for asymmetric grafting in nanomaterials engineering.
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- Award ID(s):
- 1720595
- PAR ID:
- 10434650
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1038/s41467-022-34246-0
