Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.
Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell's central cavity. This "quantum rattle" structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.nanomedicine | hybrid nanoparticle | cancer nanotechnology | gold quantum dots | mesoporous silica A lthough gold's potential in nanotechnology has been recognized for many decades (1, 2), new insights into the unique properties of gold nanoparticles (NPs) of less than 2 nm have just recently started to emerge (3, 4). Such extremely small gold NPs could be transformative for a broad set of applications ranging from energy production and storage to catalysis and health care (3). As the size of gold NPs decreases below 2 nm, the quantization of their conduction band leads to molecule-like properties (3). These quantum-sized gold NPs (or gold quantum dots, AuQDs) absorb light in the near-infrared (NIR) biological window (650-900 nm) (2) and convert it into photons and heat (5). Furthermore, whereas bulk gold is diamagnetic, some AuQDs exhibit magnetic properties (4, 6). However, the clear therapeutic and imaging potential of AuQDs in vivo has been undermined by their unfavorable biointeractions and lack of stability in aqueous solvents (5, 7). In biological environments AuQDs tend to aggregate rapidly, reverting to larger gold nanoparticles (AuNPs) (8) and/or bind to protein, which negatively affects their cytotoxicity (7). To retain their advantages, AuQDs require a protective, stabilizing framework that allows proficient biological interactions.Recently, new emphasis has been placed on hybrid NP systems, where multiple nanomaterials are assembled to create multimodal systems that exhibit the combined qualities of the component modules (9-11). These constructs promise to integrate various functionalities by incorporating different nanomaterials into a single, efficient, multimodal system (12, 13). However, these systems usually accumulate the specific functionalities of their component modules through multiple steps in their ...
Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location‐ and dose‐dependent. A NO delivery platform that directly targets the resistance‐generating region of the conventional outflow pathway and locally liberates a controlled dose of NO is reported. An increase in outflow facility (decrease in IOP) is demonstrated in a mouse model.
Membrane fusion is a process of fundamental importance in biological systems that involves highly selective recognition mechanisms for the trafficking of molecular and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of biosensor development holds great potential for amplified detection because relatively few highly discriminating targets lead to fusion and an accompanied engagement of a large payload of signal‐generating molecules. In this work, sequence‐specific DNA‐mediated liposome fusion is used for the highly selective detection of microRNA. The detection of miR‐29a, a known flu biomarker, is demonstrated down to 18 nm within 30 min with high specificity by using a standard laboratory microplate reader. Furthermore, one order of magnitude improvement in the limit of detection is demonstrated by using a novel imaging technique combined with an intensity fluctuation analysis, which is coined two‐color fluorescence correlation microscopy.
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