Zuwu Wei

Tumor Microenvironment Activable Self-Assembled DNA Hybrids for pH and Redox Dual-Responsive Chemotherapy/PDT Treatment of Hepatocellular Carcinoma

Smart self‐assembled “Turn‐ON” DNA hybrids are employed, which could respond to tumor microenvironment stimuli for cancer cell specific real‐time fluorescence imaging, tumor‐specific synergistic photodynamic therapy and chemotherapy in hepatocellular carcinoma.

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticles stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

Glutathione responsive micelles incorporated with semiconducting polymer dots and doxorubicin for cancer photothermal-chemotherapy

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challenge up to now. This study aims to on-demand remotely manipulate RNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein (P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly[2-( N, N-dimethylaminoethyl)methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable o-nitrobenzyl ester derivative-caged DOX is loaded into the inner pores of the PMSN. The PMSN is found to be effectively internalized by MDR cancer cells, and the release of the shRNA and DOX is demonstrated to be independently regulated by 405 and 365 nm light irradiations due to selectively cleaved coumarin and o-nitrobenzyl ester, resulting in enhanced drug retention, and finally bring out optimized and significantly improved chemotherapeutic effects both in vitro and in vivo for MDR cancer treatment, which might hold extensive application prospects in MDR cancer treatment in future.

A highly stable and biocompatible optical bioimaging nanoprobe based on carbon nanospheres

In this report, a facile one-step synthesis strategy has been developed for producing fluorescent carbon nanospheres (CNs) using lactobionic acid (LBA) as a precursor. The resulting CNs are highly stable in aqueous solution with an average size of 120 nm. The obtained CNs contained large amounts of –OH and –COOH on their surfaces which will facilitate further functionalization for more additional usage. In addition, carbon nanospheres possess an intrinsic fluorescence property so they can be used for fluorescence imaging. Our CNs exhibited remarkable photoluminescence properties and low cytotoxicity which can be used to label living cells with high efficiency, suggesting potential applications in biolabeling and bioimaging. In brief, we developed novel fluorescent carbon nanospheres with high stability, biocompatibility and labeling efficiency for cell imaging, as well as abundant active groups on their surface for further modifications.

Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle

Abstract Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO2-ZrO2/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO2-ZrO2/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.

Core-shell NaGdF 4 @CaCO 3 nanoparticles for enhanced magnetic resonance/ultrasonic dual-modal imaging via tumor acidic micro-enviroment triggering

For cancer diagnosis, a paramount challenge still exists in the exploring of methods that can precisely discriminate tumor tissues from their surrounding healthy tissues with a high target-to-background signal ratio. Here, we report a NaGdF4@CaCO3-PEG core-shell nanoparticle which has the tumor acidic microenvironment enhanced imaging signals of ultrasound and magnetic resonance. Under the acidic conditions, the CaCO3 shell will gradually dissolve which then facilitate the interaction of NaGdF4 with the external aqueous environment to enhance water proton relaxation. Meanwhile, the CO2 bubbles generated by the CaCO3 dissolvement will generate strong elastic echo for US detection. The core-shell structure of NaGdF4@CaCO3-PEG can be observed by TEM, and its composition can be determined by STEM. The acid triggered generation of CO2 bubbles and the enhancement of MRI signal could be demonstrated in vitro, and the excellent dual-modal magnetic resonance/ultrasonic cancer imaging abilities of NaGdF4@CaCO3-PEG could be also proved at the tumor site in vivo. The here described proof-of-concept nanoparticles with pH triggered magnetic resonance/ultrasonic dual-modal imaging enhancement, may serve as a useful guide to develop various molecular imaging strategies for cancer diagnosis in the future.