Biomolecules adsorbed on nanoparticles are known to confer a biological identity to nanoparticles, mediating the interactions with cells and biological barriers. However, how these molecules are presented on the particle surface in biological milieu remains unclear. The central aim of this study is to identify key protein recognition motifs and link them to specific cell-receptor interactions. Here, we employed an immuno-mapping technique to quantify epitope presentations of two major proteins in the serum corona, low-density lipoprotein and immunoglobulin G. Combining with a purpose-built receptor expression system, we show that both proteins present functional motifs to allow simultaneous recognition by low-density lipoprotein receptor and Fc-gamma receptor I of the corona. Our results suggest that the “labeling” of nanoparticles by biomolecular adsorption processes allows for multiple pathways in biological processes in which they may be “mistaken” for endogenous objects, such as lipoproteins, and exogenous ones, such as viral infections.

In biomedical science among several other growing fields, the detection of specific biological agents or biomolecular markers, from biological samples is crucial for early diagnosis and decision-making in terms of appropriate treatment, influencing survival rates. In this regard, immunosensors are based on specific antibody-antigen interactions, forming a stable immune complex. The antigen-specific detection antibodies (i.e., biomolecular recognition element) are generally immobilized on the nanomaterial surfaces and their interaction with the biomolecular markers or antigens produces a physico-chemical response that modulates the signal readout. Lowering the detection limits for particular biomolecules is one of the key parameters when designing immunosensors. Thus, their design by combining the specificity and versatility of antibodies with the intrinsic properties of nanomaterials offers a plethora of opportunities for clinical diagnosis. In this review, we show a comprehensive set of recent developments in the field of nanoimmunosensors and how they are progressing the detection and validation for a wide range of different biomarkers in multiple diseases and what are some drawbacks and considerations of the uses of such devices and their expansion.

Nanoparticles (NPs) functionalized with two active targeting ligands have been proposed in drug delivery for their promising capability to stimulate different pathways with one object. Due to the multivalency, the construction and analysis of the effective surface of such bifunctional nanoparticles, however, is significantly more complex than for nanoparticles bearing only one ligand. Here, we optimize construction and analysis of bifunctional NPs containing recognizable combinations of human serum albumin (HSA), transferrin (Tf), and epidermal growth factor (EGF) on fluorescent silica NPs grafted via common polyethylene glycol (PEG) linkers as a model system. Combined with an overall protein quantification, a mapping of exposed recognizable sequences using monoclonal antibodies conjugated to gold nanoparticles (AuNPs) or quantum dots (QDs) for enhanced spectroscopic and microscopic detection revealed that active protein sequences can be one to two orders of magnitude lower than overall conjugated proteins while possessing specific cellular recognition. In addition, we found that common conjugation strategies lead to a large excess of non-specifically compared to covalently bound ligands and instabilities that may impact targeting. These can be avoided by certain synthetic conditions presented here for effective exploitation of multivalent surfaces in nanomedicine.

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found to represent a unique population of cells, distinct from the majority of tissue macrophages. Monocytes and intestinal macrophages seem now to be the only monocyte/macrophage populations that originate primarily from adult bone marrow. To obtain a better view of the biological function of monocytes and how they differ from tissue macrophages, we have performed a quantitative analysis of its transcriptome in vivo and after in vitro stimulation with E. coli LPS. The monocytes rapidly responded to LPS by producing extremely high amounts of mRNA for the classical inflammatory cytokines, IL-1α, IL-1β, IL-6 and TNF-α, but almost undetectable amounts of other cytokines. IL-6 was upregulated 58,000 times, from almost undetectable levels at baseline to become one of the major transcripts already after a few hours of cultivation. The cells also showed very strong upregulation of a number of chemokines, primarily IL-8, Ccl2, Ccl3, Ccl3L3, Ccl20, Cxcl2, Cxcl3 and Cxcl4. IL-8 became the most highly expressed transcript in the monocytes already after four hours of in vitro culture in the presence of LPS. A high baseline level of MHC class II chains and marked upregulation of super oxide dismutase (SOD2), complement factor B, complement factor C3 and coagulation factor 3 (F3; tissue factor) at four hours of in vitro culture were also observed. This indicates a rapid protective response to high production of oxygen radicals, to increase complement activation and possibly also be an inducer of local coagulation. Overall, these findings give strong support for monocytes acting primarily as potent mobile sensors of infection and rapid activators of a strong inflammatory response.

Since it is now possible to make, in a controlled fashion, an almost unlimited variety of nanostructure shapes, it is of increasing interest to understand the forms of biological control that nanoscale shape allows. However, a priori rational investigation of such a vast universe of shapes appears to present intractable fundamental and practical challenges. This has limited the useful systematic investigation of their biological interactions and the development of innovative nanoscale shape-dependent therapies. Here, we introduce a concept of biologically relevant inductive nanoscale shape discovery and evaluation that is ideally suited to, and will ultimately become, a vehicle for machine learning discovery. Combining the reproducibility and tunability of microfluidic flow nanochemistry syntheses, quantitative computational shape analysis, and iterative feedback from biological responses in vitro and in vivo, we show that these challenges can be mastered, allowing shape biology to be explored within accepted scientific and biomedical research paradigms. Early applications identify significant forms of shape-induced biological and adjuvant-like immunological control.