Xiaoran Deng

UV-Emitting Upconversion-Based TiO2 Photosensitizing Nanoplatform: Near-Infrared Light Mediated in Vivo Photodynamic Therapy via Mitochondria-Involved Apoptosis Pathway

Photodynamic therapy (PDT) is a promising antitumor treatment that is based on the photosensitizers that inhibit cancer cells by yielding reactive oxygen species (ROS) after irradiation of light with specific wavelengths. As a potential photosensitizer, titanium dioxide (TiO2) exhibits minimal dark cytotoxicity and excellent ultraviolet (UV) light triggered cytotoxicity, but is challenged by the limited tissue penetration of UV light. Herein, a novel near-infrared (NIR) light activated photosensitizer for PDT based on TiO2-coated upconversion nanoparticle (UCNP) core/shell nanocomposites (UCNPs@TiO2 NCs) is designed. NaYF4:Yb(3+),Tm(3+)@NaGdF4:Yb(3+) core/shell UCNPs can efficiently convert NIR light to UV emission that matches well with the absorption of TiO2 shells. The UCNPs@TiO2 NCs endocytosed by cancer cells are able to generate intracellular ROS under NIR irradiation, decreasing the mitochondrial membrane potential to release cytochrome c into the cytosol and then activating caspase 3 to induce cancer cell apoptosis. NIR light triggered PDT of tumor-bearing mice with UCNPs@TiO2 as photosensitizers can suppress tumor growth efficiently due to the better tissue penetration than UV irradiation. On the basis of the evidence of in vitro and in vivo results, UCNPs@TiO2 NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy.

Aptamer-Mediated Up-conversion Core/MOF Shell Nanocomposites for Targeted Drug Delivery and Cell Imaging

Multifunctional nanocarriers for targeted bioimaging and drug delivery have attracted much attention in early diagnosis and therapy of cancer. In this work, we develop a novel aptamer-guided nanocarrier based on the mesoporous metal-organic framework (MOF) shell and up-conversion luminescent NaYF4:Yb3+/Er3+ nanoparticles (UCNPs) core for the first time to achieve these goals. These UCNPs, chosen as optical labels in biological assays and medical imaging, could emit strong green emission under 980 nm laser. The MOF structure based on iron (III) carboxylate materials [MIL-100 (Fe)] possesses high porosity and non-toxicity, which is of great value as nanocarriers for drug storage/delivery. As a unique nanoplatform, the hybrid inorganic-organic drug delivery vehicles show great promising for simultaneous targeted labeling and therapy of cancer cells.

A Hollow-Structured CuS@Cu2S@Au Nanohybrid: Synergistically Enhanced Photothermal Efficiency and Photoswitchable Targeting Effect for Cancer Theranostics

It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow-structured CuS@Cu2 S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu2 S@Au under 808 nm near-infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu2 S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal-isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg-Gly-Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu2 S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo- and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real-time imaging, which provides a versatile platform for multifunctional theranostics and stimuli-responsive targeted cancer therapy.

Synthesis and Optimization of MoS2@Fe3O4‐ICG/Pt(IV) Nanoflowers for MR/IR/PA Bioimaging and Combined PTT/PDT/Chemotherapy Triggered by 808 nm Laser

Elaborately designed biocompatible nanoplatforms simultaneously achieving multimodal bioimaging and therapeutic functions are highly desirable for modern biomedical applications. Herein, uniform MoS2 nanoflowers with a broad size range of 80–180 nm have been synthesized through a facile, controllable, and scalable hydrothermal method. The strong absorbance of MoS2 nanoflowers at 808 nm imparts them with high efficiency and stability of photothermal conversion. Then a novel multifunctional composite of MoS2@Fe3O4‐ICG/Pt(IV) (labeled as Mo@Fe‐ICG/Pt) is designed by covalently grafting Fe3O4 nanoparticles with polyethylenimine (PEI) functionalized MoS2, and then loading indocyanine green molecules (ICG, photosensitizers) and platinum (IV) prodrugs (labeled as Pt(IV) prodrugs) on the surface of MoS2@Fe3O4. The resulting Mo@Fe‐ICG/Pt nanocomposites can achieve excellent magnetic resonance/infrared thermal/photoacoustic trimodal biomaging as well as remarkably enhanced antitumor efficacy of combined photothermal therapy, photodynamic therapy, and chemotherapy triggered by a single 808 nm NIR laser, thus leading to an ideal nanoplatform for cancer diagnosis and treatment in future.

808 nm near-infrared light controlled dual-drug release and cancer therapy in vivo by upconversion mesoporous silica nanostructures

The design of stimuli-responsive drug delivery systems has attracted much attention to improve therapeutic efficacy for clinical applications. Here an 808 nm NIR light responsive dual-drug system was designed for cancer treatment both in vitro and in vivo. Mesoporous silica coated NaYF4:Yb0.4/Tm0.02@NaGdF4:Yb0.1@NaNdF4:Yb0.1 (UCNPs) with a core-shell structure (labeled as UCNPs@mSiO2) was prepared and loaded with the antitumor drug doxorubicin (DOX). The surface of the composite was functionalized with β-cyclodextrin rings bridged by the light cleavable platinum(iv) pro-drug, thus blocking DOX inside the mesopores of silica. When excited by 808 nm NIR light, the emitted UV light from the UCNPs was used to activate the platinum(iv) pro-drug to gain higher toxicity platinum(ii) complexes and open the mesopores of silica (at the same time) to release DOX molecules. Both DOX and platinum(ii) complexes can kill cancer cells. This dual-drug delivery system may represent a new avenue for the application of UCNPs in photoactivated cancer therapy.

808 nm light responsive nanotheranostic agents based on near-infrared dye functionalized manganese ferrite for magnetic-targeted and imaging-guided photodynamic/photothermal therapy

Near-infrared (NIR) light induced phototherapy has attracted considerable attention due to its deep therapeutic depth. To improve the therapeutic outcome and address non-selective side effects, the combination of complementary phototherapeutic strategies in a single nanoagent with precise targeting ability may provide an effective approach for cancer therapy. Thus we have developed an 808 nm NIR light triggered nanosystem based on IR806 dye functionalized MnFe2O4 (MFO-IR) for synchronous magnetic targeted and magnetic resonance (MR) imaging guided in vivo photodynamic/photothermal synergistic therapy. In this construction strategy, carboxylic acid functionalized NIR dye IR806 is explored as an 808 nm NIR-excited photosensitizer (PS) for the first time, which can also provide a conjugation site for MnFe2O4 nanoparticles (MFO NPs). Here, monodisperse MFO NPs have multiple capacities as dye carriers, targeting ligands, MRI contrast agents and photothermal agents. MFO-IR nanocomposites (NCs) with negligible toxicity present efficient NIR-mediated photothermal damage and ROS cytotoxicity via the relevant in vitro experimental investigations. With ideal magnetic targeting effects and remarkable NIR light-responsive properties, these MFO-IR NCs exhibit high in vivo tumor localization and could destroy subcutaneous solid tumors completely under an external magnetic field and 808 nm laser irradiation. Consequently, this magnetic nanosystem has great potential for simultaneous diagnosis and precise cancer phototherapy.

Multifunctional polyelectrolyte multilayers coated onto Gd2O3:Yb3+,Er3+@MSNs can be used as drug carriers and imaging agents

Mesoporous silica nanoparticles (MSNs) were firstly functionalized with upconversion luminescent Gd2O3:Yb3+,Er3+ via the Pechini sol–gel method. Then, polyelectrolyte multilayers (PEM) composed of poly(allyamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) were coated onto the Gd2O3:Yb3+,Er3+@MSNs using a layer-by-layer (LbL) technique to achieve the pH-responsive properties of the nanocarriers. PEM@Gd2O3:Yb3+,Er3+@MSNs loaded with doxorubicin hydrochloride (DOX) showed pH-responsive release and higher cytotoxicity towards MCF-7 breast cancer cells in vitro. Nanocomposites functionalized with Gd2O3:Yb3+,Er3+ can serve as T1-weighted magnetic resonance imaging (MRI) contrast agents. Nanoparticles emitting red signals under 980 nm laser excitation are suitable for use in potential bioimaging applications. The upconversion luminescent (UCL) intensity of PEM-coated nanocomposites can be adjusted by controlling the number of layers of the PAH/PSS coating. The PEM@Gd2O3:Yb3+,Er3+@MSNs can be used as a potential drug delivery system for MRI, UCL imaging, and pH-responsive chemotherapy.

Rational Design of Multifunctional Fe@γ‐Fe2O3@H‐TiO2 Nanocomposites with Enhanced Magnetic and Photoconversion Effects for Wide Applications: From Photocatalysis to Imaging‐Guided Photothermal Cancer Therapy

Titanium dioxide (TiO2 ) has been widely investigated and used in many areas due to its high refractive index and ultraviolet light absorption, but the lack of absorption in the visible-near infrared (Vis-NIR) region limits its application. Herein, multifunctional Fe@γ-Fe2 O3 @H-TiO2 nanocomposites (NCs) with multilayer-structure are synthesized by one-step hydrogen reduction, which show remarkably improved magnetic and photoconversion effects as a promising generalists for photocatalysis, bioimaging, and photothermal therapy (PTT). Hydrogenation is used to turn white TiO2 in to hydrogenated TiO2 (H-TiO2 ), thus improving the absorption in the Vis-NIR region. Based on the excellent solar-driven photocatalytic activities of the H-TiO2 shell, the Fe@γ-Fe2 O3 magnetic core is introduced to make it convenient for separating and recovering the catalytic agents. More importantly, Fe@γ-Fe2 O3 @H-TiO2 NCs show enhanced photothermal conversion efficiency due to more circuit loops for electron transitions between H-TiO2 and γ-Fe2 O3 , and the electronic structures of Fe@γ-Fe2 O3 @H-TiO2 NCs are calculated using the Vienna ab initio simulation package based on the density functional theory to account for the results. The reported core-shell NCs can serve as an NIR-responsive photothermal agent for magnetic-targeted photothermal therapy and as a multimodal imaging probe for cancer including infrared photothermal imaging, magnetic resonance imaging, and photoacoustic imaging.

Thiol–Ene Click Reaction as a Facile and General Approach for Surface Functionalization of Colloidal Nanocrystals

Oleic acid (OA) and/or oleylamine (OAm) are generally used as the surface ligands for stabilization of inorganic nanocrystals (NCs). The hydrophobic and inert surface of the NCs limits their applications such as in biomedical areas. Hence, surface modifications are essential in many physical and chemical processes. Here, a facile and versatile strategy is reported for the modification of NCs by ultraviolet-induced thiol-ene chemistry, in which thiol-terminated poly(ethylene glycol) (HSPEG) and its derivatives can react directly with double bonds in OA/OAm ligands to form covalent linking within one step. Through this strategy, various hydrophobic NCs with different compositions and morphologies are able to be transferred into water combining with functionalization of active groups. As a proof-of-concept, this strategy is successfully used to construct a sensor for detecting avidin based on upconverting luminescence analysis. Therefore, this strategy provides a new tool for designing and tuning the surface properties of NCs for different applications.

Multifunctional chitosan modified Gd2O3:Yb3+,Er3+@nSiO2@mSiO2 core/shell nanoparticles for pH responsive drug delivery and bioimaging

Gd2O3:Yb3+,Er3+@nSiO2@mSiO2 (Gd@mSi) core/shell structure nanospheres were synthesized through a sol–gel method. Then biocompatible polysaccharide chitosan (CS) was grafted onto the surface of the nanoparticles to fabricate a pH responsive CS@Gd@mSi system. Furthermore, cancer targeting ligand folic acid (FA) was modified through the abundant amino groups on the chitosan polymer shell. The nanospheres with a Gd2O3:Yb3+,Er3+ core can be candidates for T1-weighted magnetic resonance imaging (MRI) contrast agents. The CS decorated nanocomposites showing good biocompatibility and red emission under 980 nm laser excitation can be potential candidates for bioimaging in vitro. FA modified nanospheres loaded with doxorubicin hydrochloride (DOX) show higher cytotoxicity for HeLa cells in vitro compared with those nanoparticles with chitosan shells only and pure DOX. The CS@Gd@mSi system can be a potential drug carrier with MRI, UCL, and finely controlled pH-dependent drug release properties.