Creating secondary nanostructures from fundamental building blocks with simultaneous high loading capacity and well-controlled size/uniformity, is highly desired for nanoscale synergism and integration of functional units. Here a novel strategy is reported for hydrophobic quantum dots (QDs) assembley with porous templates, to form pitaya-type fluorescent silica colloids with densely packed and intact QDs throughout the silica matrix. The mercapto-terminated dendritic silica spheres with highly accessible centralradial pores and metal-affinity interior surface, are adopted as a powerful absorbent host for direct immobilization of QDs from organic phase with high loading capacity. The alkylsilane mediated silica encapsulation prevents QDs' optical degradation induced by ligand exchange and favors the homogeneous silica shell formation. These multiple QD embedded silica spheres exhibit good compatibility for different colored QDs with well-preserved fluorescence, high colloidal/optical stability, and versatile surface functionality. It is demonstrated that after integration with a lateral flow strip platform, these silica colloids provide an ultrasensitive, specific, and robust immunoassay for C-reaction protein in clinical samples as promising fluorescent reporters.

Fluorescence barcoding based on nanoparticles provides many advantages for multiparameter imaging. However, creating different concentration-independent codes without mixing various nanoparticles and by using single-wavelength excitation and emission for multiplexed cellular imaging is extremely challenging. Herein, we report the development of quantum dots (QDs) with two different SiO shell thicknesses (6 and 12 nm) that are coated with two different lanthanide complexes (Tb and Eu). FRET from the Tb or Eu donors to the QD acceptors resulted in four distinct photoluminescence (PL) decays, which were encoded by simple time-gated (TG) PL intensity detection in three individual temporal detection windows. The well-defined single-nanoparticle codes were used for live cell imaging and a one-measurement distinction of four different cells in a single field of view. This single-color barcoding strategy opens new opportunities for multiplexed labeling and tracking of cells.

Integrating multiple discrete functionalities into hollow-mesoporous architecture with distinctive electronic/magnetic property is of particular interest for building multifunctional drug carriers with complementary theranostic modalities. In this article, the "non-contact" incorporation of gold nanorod (GNR) into porous magnetic nanoshell is achieved via yolk−shell structure, which was intrinsically different from previous direct chemical or heterogeneous conjugation of the two components. The highly preserved plasmonic feature of GNRs enabled photothermal induced photoacoustic imaging and hyperthermia capabilities. The magnetic shell consisted of stacked primary iron oxide nanocrystals yields strong superparamagnetic response with excellent permeability for magnetically targeted drug delivery. Interestingly, the special coordination between doxorubicin and iron species enabled pH/local heating dual-responsive drug release with minor leakage at neutral pH. Under the guidance of magnetic resonance/photoacoustic dual-modal imaging and magnetically tumor targeting using the nanoagents, the photothermal-chemo synergistic therapy was conducted via near-infrared laser for highly efficient tumor eradication.

To enable the large-scale synthesis of coibamide A, we developed an improved synthetic strategy for this class of cyclodepsipeptide. The versatility of the synthetic procedure was demonstrated by the preparation of a series of designed coibamide A analogues, which enabled the preliminary structure−activity relationship (SAR) studies for this compound. Although most modifications of coibamide A resulted in decrease or loss of the antiproliferativity, we found that versatile substitution at position 3 was well tolerated. Remarkably, a simplified analogue, [MeAla3-MeAla6]-coibamide (1f), not only showed nearly the same inhibition as coibamide A against the tested cancer cells but also significantly inhibited tumor growth in vivo. The improved synthetic strategy and the relevant trends of SAR disclosed in this study will be valuable for further optimization of the overall profile of coibamide A.

Exploring multifunctional nanomaterials from biocompatible constituents, with integrated imaging and targeted combination therapeutic modalities of tumors in vivo, provides great prospects for clinical cancer theranostic applications. Here, we report a combination strategy for functionalization of polydopamine (PDA) nanohosts with magnetic response and stimuli-controlled drug release capabilities for in vivo cancer theranostic. The high processability of PDA as nanotemplates and surface coating layers as well as its natural affinity to metals facilitated the sandwich of a compact iron oxide nanoparticle layer into the PDA matrix, realizing enhanced near-infrared (NIR) photothermal conversion and strong superparamagnetic responsiveness. Additionally, the high reactivity of the PDA surface allowed facile linkage with reduction-responsive prodrugs and polyethylene glycol chains for in vivo chemotherapy of cancer. Under the magnetic resonance imaging/photoacoustic imaging dual-modal tumor imaging and active magnetic tumor targeting of the nanoagents in vivo, the effective tumor eradication was achieved via synergetic NIR photothermal ablation and anticancer drug delivery.

Exploring signal amplification strategies to enhance the sensitivity of lateral flow immunoassay (LFIA) is of great significance for point-of-care (POC) testing of low-concentrated targets in the field of in vitro diagnostics. Here, a highly-sensitive LFIA platform using compact and hierarchical magnetofluorescent assemblies as both target-enrichment substrates and optical sensing labels is demonstrated. The large-pored dendritic templates are utilized for high-density incorporation of both superparamagnetic iron oxide nanoparticles (IOs) and quantum dots (QDs) within the vertical channels. The hierarchical structure is built via affinity-driven assembly of IOs and QDs from organic phase with silica surface and mercapto-organosilica intermediate layer, respectively. The sequential assembly with central-radial channels enables 3D loading of dual components and separately controlling of discrete functionalities. After the alkyl-organosilica encapsulation and silica sealing, the composite spheres exhibit high stabilities and compatibility with LFIA for procalcitonin (PCT) detection. With the assistance of liquid-phase antigen-capturing, magnetic enrichment, and fluorescence-signal amplification, a limit of detection of 0.031 ng mL −1 for PCT is achieved with a linear range from 0.012 to 10 ng mL −1 . The current LFIA is robust and validated for PCT detection in real serum, which holds great diagnostic significance for precise guidance of antibiotic therapy with POC manner.

A multifunctional drug delivery vehicle consisting of a tubular shaped silica host, a compact superparamagnetic iron oxide nanoparticle layer and a hyaluronic acid surface coating was developed as a theranostic platform, for in vivo MR imaging and magnetically guided/cancer targeted drug delivery.

Lateral flow immunoassay (LFIA), as a prominent point-of-care (POC) test platform, has been extensively adopted for rapid, on-site, and facile diagnosis of pathogen infections and disease biomarkers. Exploring novel structured optical labels of LFIA with amplified signal and complementary detection modes favors the sensitive and flexible POC diagnosis. Here, bimodal labels with both colorimetric and fluorescent readout were fabricated via a layered sequential assembly strategy based on affinity templates and hydrophobic metal-containing nanounits. High-quality colorimetric and fluorescent nanoparticles were densely incorporated into the colloidal supports and confined in separated regions, without interfering with each other. The hierarchical integration of gold nanoparticles and quantum dots with high loading density and good optical preservation realized dual readout and amplified signals from the assemblies of individual single nanoparticles. The "all-in-one" optical labels allowed both colorimetric and fluorescent detection of cystatin C (Cys C) after surface conjugation with antibodies. The LFIA strips revealed noninterfering dual signals for both visual inspection and quantitative detection of Cys C via the naked eye and portable devices, respectively. The limits of detection by colorimetric and fluorescent modes were 0.61 and 0.24 ng mL −1 , respectively. The novel LFIA platform demonstrated sensitive, specific, and reproducible POC testing of biomarkers with flexible detection modes and was reliable for clinical diagnosis.