An official website of the United States government
Colloidal nanoparticle assembly methods can produce intricate superlattice structures and often use knowledge of atomic crystallization behaviors to guide their design. While this analogy has enabled multiple routes to programming colloidal crystallization thermodynamics, fewer tools or strategies exist to manipulate nanoparticle superlattice growth kinetics in a controlled manner. Here we investigate how small molecule additives can be used to modulate the thermodynamics and kinetics of supramolecular-chemistry-driven nanoparticle assembly. Specifically, we introduce monovalent binding agents into the superlattice growth solution that compete with the multivalent interparticle bonding interactions driving particle assembly, thereby altering interparticle bond strength by reducing the number of bridging complexes formed between particles. In this manner, the assemblies can be steered to avoid kinetic traps and crystallize into faceted single crystals under isothermal conditions, alleviating the need for precise thermal control that has conventionally been required to produce large, faceted crystals in prior assembly methods.
more »
« less
Quantifying and controlling bond multivalency for advanced nanoparticle targeting to cells
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.
more »
« less
- Award ID(s):
- 1929565
- PAR ID:
- 10394457
- Date Published:
- Journal Name:
- Nano Convergence
- Volume:
- 8
- Issue:
- 1
- ISSN:
- 2196-5404
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Background Nanoparticles (NPs) hold promise as alternatives to antibiotics in the fight against multi-drug-resistant bacteria. However, concerns about their cytotoxicity, particularly their effects on mammalian cells, must be thoroughly addressed to ensure therapeutic safety. Amphiphilic Janus NPs, which have segregated hydrophobic and polycationic ligands on two hemispheres, have previously been shown to exhibit potent antibacterial activity. Methods In this study, we evaluated the cytotoxicity of amphiphilic Janus NPs in immune and cancer cell lines. Cytotoxicity assays were performed to assess the effects of Janus NPs on cell viability and membrane integrity, with a particular focus on how internalization of the nanoparticles influenced cellular responses. Results The results revealed that both immune and cancer cells exhibited negligible cytotoxic effects when exposed to Janus NPs. However, phagocytic immune cells demonstrated greater susceptibility to membrane damage and viability loss, suggesting that internalization plays a significant role in nanoparticle-induced cytotoxicity. Conclusions Amphiphilic Janus NPs show great potential as highly effective antibacterial agents with minimal cytotoxicity. While immune cells may be more vulnerable to nanoparticle-induced damage due to their internalization capacity, these findings support the further investigation of Janus NPs for clinical applications.more » « less
-
RhoU and RhoV are members of the Rho family of small GTPases that comprise their own subfamily. RhoUV GTPases are classified as atypical due to the kinetics of their GTP/GDP binding cycles. They also possess unique N- and C-termini that regulate their subcellular localization and activity. RhoU and RhoV have been linked to cytoskeletal regulation, cell adhesion, and cell migration. They each exhibit distinct expression patterns during embryonic development and diseases such as cancer metastasis, suggesting they have specialized functions. In this review, we will discuss the known functions of RhoU and RhoV, with a focus on their roles in early development, organogenesis, and disease.more » « less
-
Cancer therapy is a significant challenge due to insufficient drug delivery to the cancer cells and non-selective killing of healthy cells by most chemotherapy agents. Nano-formulations have shown great promise for targeted drug delivery with improved efficiency. The shape and size of nanocarriers significantly affect their transport inside the body and internalization into the cancer cells. Non-spherical nanoparticles have shown prolonged blood circulation half-lives and higher cellular internalization frequency than spherical ones. Nanodiscs are desirable nano-formulations that demonstrate enhanced anisotropic character and versatile functionalization potential. Here, we review the recent development of theranostic nanodiscs for cancer mitigation ranging from traditional lipid nanodiscs encased by membrane scaffold proteins to newer nanodiscs where either the membrane scaffold proteins or the lipid bilayers themselves are replaced with their synthetic analogues. We first discuss early cancer detection enabled by nanodiscs. We then explain different strategies that have been explored to carry a wide range of payloads for chemotherapy, cancer gene therapy, and cancer vaccines. Finally, we discuss recent progress on organic–inorganic hybrid nanodiscs and polymer nanodiscs that have the potential to overcome the inherent instability problem of lipid nanodiscs.more » « less
-
Clays have been used as early as 2500 BC in human civilization for medicinal purposes. The ease of availability, biocompatibility, and versatility of these unique charged 2D structures abundantly available in nature have enabled the extensive applications of clays in human history. Recent advances in the use of clays in nanostructures and as components of polymer clay nanocomposites have exponentially expanded the use of clays in medicine. This review covers the details of structures and biomedical applications of several common clays, including montmorillonite, LAPONITE®, kaolinite, and halloysite. Here we describe the applications of these clays in wound dressings as hemostatic agents in drug delivery of drugs for cancer and other diseases and tissue engineering. Also reviewed are recent experimental and modeling studies that elucidate the impact of clay structures on cellular processes and cell adhesion processes. Various mechanisms of clay-mediated bioactivity, including protein localization, modulation of cell adhesion, biomineralization, and the potential of clay nanoparticles to impact cell differentiation, are presented. We also review the current developments in understanding the impact of clays on cellular responses. This review also elucidates new emerging areas of use of nanoclays in osteogenesis and the development of in vitro models of bone metastasis of cancer.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1186/s40580-021-00288-1
