Smart design of exquisite multidimensional multilayered sand-clock-like upconversion nanostructures with ultrabright luminescence as efficient luminescence probes for bioimaging application.

A facile scalable approach is presented for the rational design of multidimensional, multilayered sand-clock-like UCNPs (denoted as UCCKs) bounded with high index facets, with a tunable Nd3+ content, and without a template or multiple complicated reaction steps. This was achieved using the seed-mediated growth and subsequent longitudinal direction epitaxial growth with the assistance of oleic acid and NH4F. The as-formed UCCKs composed of an inner layer (NaYF4:Yb,Er,Ca), an intermediate layer (NaYF4:Yb,Ca), and an outer layer (NaNdF4:Yb,Ca). The outer shell, enriched with Nd3+ sensitizer, augmented the near-infrared (NIR) photon absorption, whereas the intermediate shell, enriched with Yb3+, acted as a bridge for energy transfer from Nd3+ to Er3+ emitter in the inner core alongside with precluding any deleterious energy back-transfer from Er3+ or quenching effect from Nd3+. These unique structural and compositional properties of UCCKs endowed the UCL intensity of UCCKs by 22 and 10 times higher than that of hexagonal UCNP core (NaYF4:Yb,Er,Ca) and hexagonal UCNP core-shell (NaYF4:Yb,Er,Ca@NaYF4:Yb,Ca), respectively. Intriguingly, the UCL intensity increased significantly with increasing the content of Nd3+ in the outer shell. The silica-coated UCCKs were used as excellent long-term luminescence probes for the in vitro bioimaging without any noteworthy cytotoxicity. The presented approach may pave the road for controlling the synthesis of multidimensional UCCKs for various applications. Graphical abstract We developed novel multidimensional multilayered sand-clock-like upconversion nanostructures composed of a spherical inner core (NaYF4:Yb,Er,Ca), hexagonal intermediate shell (NaYF4:Yb,Ca) and two up-down outer shell (NaNdF4:Yb,Ca) with controllable Nd3+ as an efficient and safe probe for bioimaging applications without any quenching effect.

Renal-clearable hyaluronic acid functionalized NaGdF4 nanodots with enhanced tumor accumulation.

Integration of high tumor-targeting capacity, controlling in vivo transport and low normal tissue retention into one engineered nanoparticle is a critical issue for future clinically translatable anti-cancer nanomedicines. Herein, hyaluronic acid functionalized 3.8 nm NaGdF4 nanodots (named NaGdF4 ND@HAs) have been prepared through conjugation of tryptone capped NaGdF4 nanodots (NaGdF4 ND@tryptone) with hyaluronic acid (HA, a naturally occurring glycosaminoglycan), which can recognize the overexpressed CD44 on cancer cell membranes. The as-prepared NaGdF4 ND@HAs have good paramagnetic properties (longitudinal relaxivity (r 1) = 7.57 × 10-3 M S-1) and low cytotoxicity. The in vivo experimental results demonstrate that the NaGdF4 ND@HAs can not only efficiently accumulate in mouse-bearing MDA-MB-231 tumors (ca. 5.3% injection dosage (ID) g-1 at 2 h post-injection), but also have an excellent renal clearance efficiency (ca. 75% injection dosage (ID) at 24 h post-injection). The as-prepared NaGdF4 ND@HAs have good paramagnetic properties with enhanced tumor-targeting capacity, which provides a useful strategy for the preparation of renal clearable magnetic resonance imaging (MRI) contrast agents for tumors.

Peptide-enhanced tumor accumulation of upconversion nanoparticles for sensitive upconversion luminescence/magnetic resonance dual-mode bioimaging of colorectal tumors.

Currently, it is still a great challenge to develop tumor targeting nanoparticles with high sensitivity and high resolution for improving the non-invasive detection ability of colorectal cancer (CRC) at an early stage. In this study, NaErF4:Yb@NaGdF4:Yb core@shell upconversion nanoparticles (UCNPs) were prepared with high upconversion luminescence (UCL) emission in red light region through adjusting the doping ratios of Er and Yb elements in the core. For biomedical applications, the carboxyl-terminated silica shell was introduced to transfer the as-prepared UCNPs from the organic phase to the aqueous phase, and allowed conjugation with peptide ligands derived from the l-SP5 peptide (i.e., l-SP5-H and l-SP5-C), respectively. Due to the tumor-targeting affinity of the PSP motif in the peptide ligands, the as-prepared peptide functionalized UCNPs (UCNP@SiO2-l-SP5-H and UCNP@SiO2-l-SP5-C) can be used as an active tumor targeting contrast agents for UCL/T1-weighted magnetic resonance (MR) dual-mode imaging. Both the in vitro and in vivo experimental results demonstrated that UCNP@SiO2-l-SP5-C has relatively high affinity for the HCT116 CRC subtype. Moreover, UCNP@SiO2-l-SP5-C can visualize ultra-small subcutaneous xenografted HCT116 tumors (c.a. 13 mm3 in volume) by in vivo UCL imaging. STATEMENT OF SIGNIFICANCE: 1. High red emission UCNPs were synthesized for tumor-targeting dual-mode bioimaging. 2. With tumor-binding affinity peptide, UCNP@SiO2-l-SP5-C shows high HCT116 tumor targeting ability. 3. UCNP@SiO2-l-SP5-C successfully achieves sensitive detection of ultrasmall HCT116 tumors.

Rational synthesis of three-dimensional core-double shell upconversion nanodendrites with ultrabright luminescence for bioimaging application.

Engineering the morphology of rare-earth doped NaYF4-based upconversion nanoparticles (UCNPs) can effectively tune their upconversion luminescence emission (UCLE) properties. Herein, we rationally synthesized a new class of three-dimensional upconversion core-double-shell nanodendrites (UCNDs) including an active core (NaYF4:Yb,Er,Ca) capped by a transition layer (NaYF4:Yb,Ca) and an active outer shell (NaNdF4:Yb,Ca). The high concentration of the Nd3+ sensitizer in the outer dendritic shell enhances the luminescence intensity, while the transition layer enriched with Yb3+ acts as an efficient energy migration network between the outer shell and inner core along with preventing the undesired quenching effects resulting from Nd3+. These unique structural and compositional merits enhanced the UCLE of UCNDs by 5 and 15 times relative to NaYF4:Yb,Er,Ca@NaYF4:Yb,Ca truncated core-shell UCNPs and NaYF4:Yb,Er,Ca spherical core UCNPs, respectively, under excitation at 980 nm. The SiO2-COOH layer coated UCNDs (UCND@SiO2-COOH) were successfully used as efficient long-term luminescent probes for in vitro and in vivo bioimaging without any significant toxicity. The uptake and retention of UCND@SiO2-COOH were mostly found in the liver and spleen. This study may open the way towards the preparation of three-dimensional UCND nanostructures for biomedical applications.