An official website of the United States government
The surface properties of biologically active nanoparticles (NPs) are often dictated by synthetic ligands that are grafted to the NP core to form a protecting monolayer. Ligand selection is thus critical in determining NP surface properties and corresponding interactions at the nano-bio interface, which are relevant to numerous applications including drug delivery and biosensing. However, chemically specific structure–property relationships for rationally selecting ligands to achieve desired biointeractions are largely lacking. In this Focus Article, we review the challenges associated with relating ligand chemical properties to monolayer-protected NP surface properties due to the interplay of ligand–ligand, ligand–solvent, and ligand–biomolecule interactions that are difficult to anticipate. In particular, we highlight unexpected spatially varying properties that emerge even for uniformly functionalized NPs due to the fluctuations of ligands at the nanoscale. We further review the capability of physics-based molecular simulations to reveal these unexpected behaviors, providing powerful computational methods to predict NP properties. Finally, we discuss the opportunity for such simulations to be combined with machine-learning methods to guide the computational design of monolayer-protected NPs prior to synthesis.
more »
« less
Non-equilibrium transport of nanoparticles across the lipid membrane
Development of effective strategies for the internalization of nanoparticles is essential in many applications, such as drug delivery. Most, if not all, previous studies are based on equilibrium considerations. In this work, inspired by the recent development of a pro-drug delivery strategy based on reversible esterification, we consider a non-equilibrium transport mechanism for nanoparticles of a 6 nm diameter across the lipid membrane. We divide the transport process into insertion and ejection steps, which are studied with coarse-grained models using free energy and reactive Monte Carlo simulations, respectively. The simulations show that the non-equilibrium transport efficiency is relatively insensitive to the fraction of reactive surface ligands once a modest threshold is surpassed, while the distribution pattern of different (hydrophilic, reactive and permanent hydrophobic) ligands on the nanoparticle surface has a notable impact on both the insertion and ejection steps. Our study thus supports a novel avenue for designing nanoparticles that are able to be efficiently internalized and provides a set of relevant guidelines for surface functionalization.
more »
« less
- Award ID(s):
- 2001611
- PAR ID:
- 10430353
- Date Published:
- Journal Name:
- Nanoscale
- ISSN:
- 2040-3364
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Recently, nano-based cancer therapeutics have been researched and developed, with some nanomaterials showing anticancer properties. When it comes to cancer treatment, graphene quantum dots (GQDs) contain the ability to generate 1O2, a reactive oxidative species (ROS), allowing for the synergistic imaging and photodynamic therapy (PDT) of cancer. However, due to their small particle size, GQDs struggle to remain in the target area for long periods of time in addition to being poor drug carriers. To address this limitation of GQDs, hollow mesoporous silica nanoparticles (hMSNs) have been extensively researched for drug delivery applications. This project investigates the utilization and combination of biomass-derived GQDs and Stöber silica hMSNs to make graphene quantum dots-hollow mesoporous silica nanoparticles (GQDs-hMSNs) for fluorescent imaging and dual treatment of cancer via drug delivery and photodynamic therapy (PDT). Although the addition of hMSNs made the newly synthesized nanoparticles slightly more toxic at higher concentrations, the GQDs-hMSNs displayed excellent drug delivery using fluorescein (FITC) as a mock drug, and PDT treatment by using the GQDs as a photosensitizer (PS). Additionally, the GQDs retained their fluorescence through the surface binding to hMSNs, allowing them to still be used for cell-labeling applications.more » « less
-
null (Ed.)Abstract Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.more » « less
-
Abstract Vascular‐targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly‐lactic‐co‐glycolic‐acid (PLGA)‐based multistage delivery system (MDS). MDS consists of two stages: a micron‐sized PLGA outer shell and encapsulated drug‐loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3–6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl‐Lewis‐A (sLeA) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstrates a 2.7‐fold improvement in endothelial binding compared to PLGA nanoparticles from human blood laminar flow. Overall, the presented results demonstrate successful development and characterization of MDS and suggest that MDS can serve as an effective drug carrier, which can enhance the margination of nanoparticles to the targeted vascular wall.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
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3NR00930K
