Upconversional core–shell nanostructures have gained considerable attention due to their distinct enhanced fluorescence efficiency, multifunctionality, and specific applications. Recently, we have developed a sequential growth process to fabricate unique upconversion core–shell nanoparticles. Time evolution of morphology for the NaYF4:Yb/Er@NaGdF4 nanodumbbells has been extensively investigated. An Ostwald ripening growth mechanism has been proposed to illustrate the formation of NaYF4:Yb/Er@NaGdF4 nanodumbbells. The hydrophilic NaYF4:Yb/Er@NaGdF4 core–shell nanodumbbells exhibited strong upconversion fluorescence and showed higher magnetic resonance longitudinal relaxivity (r1 = 7.81 mM–1 s–1) than commercial contrast agents (Gd-DTPA). NaYF4:Yb/Er@NaGdF4 nanodumbbells can serve as good candidates for high efficiency fluorescence and magnetic resonance imaging.Keywords: MR imaging compatibility; nanodumbbells; sequential growth; upconversion nanoparticles;

Large-size-induced long-term retention in the body has hampered the translational applications of many reported nanomedicines. Herein, we reported a multifunctional theranostic agent composed of ultrasmall poly(acrylic acid)-functionalized Ni0.85Se nanoparticles (PAA–Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA–Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency of 54.06%, which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light. Notably, the ultrasmall PAA–Ni0.85Se NPs, unlike conventional nanomaterials with larger sizes, showed reasonable body clearance within 8 h after intravenous injection. Furthermore, ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules in an acidic microenvironment, the drug-loaded (doxorubicin hydrochloride, DOX·HCl) PAA–Ni0.85Se NPs (PAA–Ni0.85Se–DOX NPs) revealed promoted drug release at acidic pH, which could be useful for acidic tumor microenvironment responsive drug delivery. Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo, PAA–Ni0.85Se–DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells. Thus, this study presents a multifunctional theranostic agent composed of ultrasmall PAA–Ni0.85Se NPs for potential cancer treatment without long-term toxicity concerns.Keywords: cancer; chemotherapy; Ni0.85Se nanoparticles; photoacoustic imaging; photothermal therapy;

Synergistic photodynamic and photothermal therapy of cancer cells is of considerable scientific and technological interest. In this work, we demonstrate a sacrificial template strategy to fabricate yolk–shell nanoparticles combining upconversion nanoparticles (UCNPs) and CuS nanoparticles. Lanthanide-doped upconversion nanoparticles of NaYF4:30% Yb,1% Nd,0.5% Er@NaYF4:20% Nd (also denoted as UCNPs) have been prepared as 808 nm light excited remote-controlled nanotransducers for in vitro cancer cell treatment. The upconversion fluorescence of the as-prepared UCNPs@CuS yolk–shell nanoparticles is completely quenched under the excitation of an 808 nm laser, which demonstrates that the energy transfer between the UCNPs and CuS is very efficient. In addition, the as-prepared UCNPs@CuS nanoparticles show higher production ability for hydroxyl radicals (˙OH) and singlet oxygen (1O2) compared to CuS hollow nanospheres of similar size. In particular, the excited shell layer (CuS) showed an enhanced photothermal effect while producing reactive oxygen species (ROS) including singlet oxygen (1O2) and hydroxyl radicals (˙OH) after being exposed to near infrared (NIR) light. Thus, the as-prepared UCNPs@CuS yolk–shell nanoparticles exhibited the synergistic effect of photothermal and photodynamic therapy of cancer cells, which resulted in significant cell death after exposure to an 808 nm laser. The synthetic strategy will provide an alternative method to fabricate other UCNP based core–shell nanoparticles for potential and important applications in bionanotechnology including theranostics, multimodal treatment, magnetic resonance imaging-guided photodynamic therapy, etc.

It is a significant challenge to develop nanoscale magnetic resonance imaging (MRI) contrast agents with high performance of relaxation. In this work, Gd3+-doped CaF2-based core–shell nanoparticles (CaF2:Yb,Er@CaF2:Gd) of sub-10 nm size were controllably synthesized by a facile sequential growth method. The as-prepared hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles modified using PEG-PAA di-block copolymer benefited from the presence of Gd only in the outer CaF2 layer of the nanoparticles, which exhibited r1 as high as 21.86 mM−1 s−1 under 3.0 T, seven times as high as that of commercially used gadopentetate dimeglumine (Gd-DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion leakage phenomenon of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles have been observed and confirmed. Clear vascular details can be observed in magnetic resonance angiography and obvious MR signal of 4T1 tumor area could be significantly improved by intravenous injection of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles at a low dosage in mice. A series of in vivo biological safety evaluations confirmed the good biocompatibility of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles, which might be employed in clinical blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.