Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers.

Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor.

Mapping Antibody Domain Exposure on Nanoparticle Surfaces Using DNA-PAINT.

Decorating nanoparticles with antibodies (Ab) is a key strategy for targeted drug delivery and imaging. For this purpose, the orientation of the antibody on the nanoparticle is crucial to maximize fragment antibody-binding (Fab) exposure and thus antigen binding. Moreover, the exposure of the fragment crystallizable (Fc) domain may lead to the engagement of immune cells through one of the Fc receptors.

Valency and affinity control of aptamer-conjugated nanoparticles for selective cancer cell targeting.

Nanoparticles (NPs) are commonly functionalized using targeting ligands to drive their selective uptake in cells of interest. Typical target cell types are cancer cells, which often overexpress distinct surface receptors that can be exploited for NP therapeutics. However, these targeted receptors are also moderately expressed in healthy cells, leading to unwanted off-tumor toxicities.

Single-Particle Functionality Imaging of Antibody-Conjugated Nanoparticles in Complex Media.

The properties of nanoparticles (NPs) can change upon contact with serum components, occluding the NP surface by forming a biomolecular corona. It is believed that targeted NPs can lose their functionality due to this biological coating, thus losing specificity and selectivity toward target cells and leading to poor therapeutic efficiency. A better understanding of how the biomolecular corona affects NP ligand functionality is needed to maintain NP targeting capabilities.

Mapping the relationship between total and functional antibodies conjugated to nanoparticles with spectrally-resolved direct stochastic optical reconstruction microscopy (SR-dSTORM).

Antibody-functionalized nanoparticles (NPs) have shown numerous benefits in drug delivery and biosensing, improving the specificity of cell targeting and analyte detection, respectively. However, one of the main challenges is the lack of control over antibody orientation on the NP surface. Popular and easy conjugation strategies, such as carbodiimide-based conjugations, lead to a random orientation of antibodies on the NPs, compromising ligand functionality and contributing to undesired biological effects and reduced target recognition.

Artificial Antigen-Presenting Cell Topology Dictates T Cell Activation.

Nanosized artificial antigen-presenting cells (aAPCs), synthetic immune cell mimics that aim to activate T cells or , offer an effective alternative to cellular immunotherapies. However, comprehensive studies that delineate the effect of nano-aAPC topology, including nanoparticle morphology and ligand density, are lacking. Here, we systematically studied the topological effects of polymersome-based aAPCs on T cell activation.

Multicolor Super-Resolution Microscopy of Protein Corona on Single Nanoparticles.

Nanoparticles represent a promising class of material for nanomedicine and molecular biosensing. The formation of a protein corona due to nonspecific particle-protein interactions is a determining factor for the biological fate of nanoparticles in vivo and strongly impacts the performance of nanoparticles when used as biosensors. Nonspecific interactions are usually highly heterogeneous, yet little is known about the heterogeneity of the protein corona that may lead to inter- and intraparticle differences in composition and protein distribution.

A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density.

Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interaction. To rationally develop selective NPs, the single-molecule quantitation of both parameters is highly desirable.

A quantitative view on multivalent nanomedicine targeting.

Although the concept of selective delivery has been postulated over 100 years ago, no targeted nanomedicine has been clinically approved so far. Nanoparticles modified with targeting ligands to promote the selective delivery of therapeutics towards a specific cell population have been extensively reported. However, the rational design of selective particles is still challenging.

A structurally diverse library of glycerol monooleate/oleic acid non-lamellar liquid crystalline nanodispersions stabilized with nonionic methoxypoly(ethylene glycol) (mPEG)-lipids showing variable complement activation properties.

Pluronic F127-stabilized non-lamellar liquid crystalline aqueous nanodispersions are promising injectable platforms for drug and contrast agent delivery. These nanodispersions, however, trigger complement activation in the human blood, where the extent of complement activation and opsonization processes may compromise their biological performance and safety. Here, we introduce a broad family of nanodispersions from glycerol monooleate (GMO) and oleic acid (OA) in different weight ratios, and stabilized with a plethora of nonionic methoxypoly(ethylene glycol) (mPEG)-lipids of different PEG chain length and variable lipid moiety (monounsaturated or saturated diglycerides or D-α-tocopheryl succinate).

Coated and Hollow Microneedle-Mediated Intradermal Immunization in Mice with Diphtheria Toxoid Loaded Mesoporous Silica Nanoparticles.

Purpose: To examine the immunogenicity of diphtheria toxoid (DT) loaded mesoporous silica nanoparticles (MSNs) after coated and hollow microneedle-mediated intradermal immunization in mice.

Methods: DT was loaded into MSNs and the nanoparticle surface was coated with a lipid bilayer (LB-MSN-DT). To prepare coated microneedles, alternating layers of negatively charged LB-MSN-DT and positively charged N-trimethyl chitosan (TMC) were coated onto pH-sensitive microneedle arrays via a layer-by-layer approach.