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The success of nanomedicines in the clinic depends on our comprehensive understanding of nano-bio interactions in tumor microenvironments, which are characterized by dense leaky microvasculature and acidic extracellular pH (pHe) values. Herein, we investigated the accumulation of ultrasmall renal-clearable gold NPs (AuNPs) with and without acidity targeting in xenograft mouse models of two prostate cancer types, PC-3 and LNCaP, with distinct microenvironments. Our results show that both sets of AuNPs could easily penetrate into the tumors but their uptake and retention were mainly dictated by the tumor microvasculature and the enhanced permeability and retention effect over the entire targeting process. On the other hand, increased tumor acidity indeed enhanced the uptake of AuNPs with acidity targeting, but only for a limited period of time. By making use of simple surface chemistry, these two effects can be synchronized in time for high tumor targeting, opening new possibilities to further improve the targeting efficiencies of nanomedicines. [ABSTRACT FROM AUTHOR]

Synergistic effects arising from the conjugation of organic dyes onto non-luminescent metal nanoparticles (NPs) have greatly broadened their applications in both imaging and sensing. Herein, we report that conjugation of a well-known pH-insensitive dye, tetramethyl-rhodamine (TAMRA), to pH-insensitive luminescent gold nanoparticles (AuNPs) can lead to an ultrasmall nanoindicator that can fluorescently report local pH in a ratiometric way. Such synergy originated from the dimerization of TAMRA on AuNPs, of which geometry was very sensitive to surface charges of the AuNPs and can be reversely modulated through protonation of surrounding glutathione ligands. Not limited to pH-insensitive dyes, this pH-dependent dimerization can also enhance the pH sensitivity of fluorescein, a well-known pH-sensitive dye, within a larger pH range, opening up a new pathway to design ultrasmall fluorescent ratiometric nanoindicators with tunable wavelengths and pH response ranges. [ABSTRACT FROM AUTHOR]

Label-free SPR is rarely used for biomarker detection in real samples due to its low sensitivity. Herein, we report a phage-based SPR (P-SPR) strategy for the detection of carcinoembryonic antigen (CEA) in undiluted serums. M13 phage is genetically engineered to display an anti-CEA single-chain variable region fragment on pIII protein for antigen targeting and to display the gold binding peptide (GBP) at the pVIII protein for gold nanoparticles (GNPs) binding to form the GNPs decorated M13 phage probe that can amplify the plasmon resonance signal. The proposed P-SPR method demonstrated ultrasensitive detection of CEA within 10 min. Under ideal conditions, P-SPR showed exceptional sensitivity with a limit of detection (LOD) of 0.83 fM, which is approximately 2000 times that of the conventional SPR and four orders of magnitude more sensitive than enzyme-linked immunosorbent assay. In particular, the proposed strategy can cross-validate the SPR results through naked-eye counting of the plaques generated by the P-SPR probes, enabling a reliable dual detection system. In addition, P-SPR scheme has excellent sensing performance for the detection of real samples at concentrations lower than LOD of ELISA. Therefore, the proposed P-SPR strategy holds potential for early detection of tumour biomarkers in liquid biopsy. [Display omitted] • Genetically engineered M13 phage-GNPs hybrid was used for SPR signal enhancement to detect CEA in undiluted serum samples. • The proposed sensing scheme achieved a LOD of 0.83 fM, which is approximately ∼21,000 times sensitive than ELISA. • This scheme enables a reliable biomarker detection system by cross-validating the result based on SPR and naked-eye counting. [ABSTRACT FROM AUTHOR]

Understanding how surface chemistry influences gold nanoparticle (AuNP) biodistribution and pharmacokinetics is critical for the design of Au-based nanoprobes for in vivo sensing and imaging. AuNPs prepared using a single surface ligand have been widely studied; however, limited work has been reported for luminescent AuNPs decorated with multiple surface ligands. Herein, we describe the synthesis and characterization of four dual-ligand luminescent AuNPs prepared using a combination of four thiol-containing ligands (GSH, MUA, tDK, tDY). The impact of surface chemistry on in vivo biodistribution and pharmacokinetics was then investigated for each dual-ligand AuNP type using a mouse model. Our results indicate that variation of one of the two surface ligands can exert a significant influence on the pharmacokinetics and biodistribution of the AuNPs. Interestingly, we observed changes in biodistribution in the lung and digestive organs, as well as blood circulation time. These results are expected to inform the future de novo design of dual-ligand luminescent AuNPs for in vivo applications. [Display omitted] [ABSTRACT FROM AUTHOR]

• Summarization of different cellular pathways of gold nanoparticles. • The effect of physiochemical properties of gold nanoparticles on cellular uptake. • Recent advances on simulation modelling of AuNPs-biomembrane interactions. • To provide a guidance for the design of AuNPs for biomedical applications. Gold Nanoparticles (AuNPs) are a class of promising nanomaterial for biomedical applications ranging from bioimaging, drug delivery to phototherapy because of their biocompatibility, easily tunable size and shape, and versatile surface modifications. In recent years, the rapid development of AuNPs in nanomedicine has made it imperative to seek fundamental understanding on their nano-biointeractions to minimize adverse effects and improve targeting/imaging efficiency. In this review, we summarize the different pathways of NPs-biomembrane interactions with a focus on AuNPs, follow by an analysis on how the physiochemical properties (size, surface charge, shape, surface ligands, and hydrophobicity etc.) of AuNPs can be involved in the mechanisms of cellular uptake. Finally, some recent advances on simulation modelling of AuNPs-biomembrane interactions and a brief outlook in the field are discussed. [ABSTRACT FROM AUTHOR]