Zhong Luo

Engineering a Hollow Nanocontainer Platform with Multifunctional Molecular Machines for Tumor-Targeted Therapy in Vitro and in Vivo

In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, α-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment.

Covalent Organic Frameworks Formed with Two Types of Covalent Bonds Based on Orthogonal Reactions

Covalent organic frameworks (COFs) are excellent candidates for various applications. So far, successful methods for the constructions of COFs have been limited to a few condensation reactions based on only one type of covalent bond formation. Thus, the exploration of a new judicious synthetic strategy is a crucial and emergent task for the development of this promising class of porous materials. Here, we report a new orthogonal reaction strategy to construct COFs by reversible formations of two types of covalent bonds. The obtained COFs consisting of multiple components show high surface area and high H2 adsorption capacity. The strategy is a general protocol applicable to construct not only binary COFs but also more complicated systems in which employing regular synthetic methods did not work.

A Preloaded Amorphous Calcium Carbonate/Doxorubicin@Silica Nanoreactor for pH‐Responsive Delivery of an Anticancer Drug

Biomedical applications of nontoxic amorphous calcium carbonate (ACC) nanoparticles have mainly been restricted because of their aqueous instability. To improve their stability in physiological environments while retaining their pH-responsiveness, a novel nanoreactor of ACC-doxorubicin (DOX)@silica was developed for drug delivery for use in cancer therapy. As a result of its rationally engineered structure, this nanoreactor maintains a low drug leakage in physiological and lysosomal/endosomal environments, and responds specifically to pHu20056.5 to release the drug. This unique ACC-DOX@silica nanoreactor releases DOX precisely in the weakly acidic microenvironment of cancer cells and results in efficient cell death, thus showing its great potential as a desirable chemotherapeutic nanosystem for cancer therapy.

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Unimolecular photoconversion of multicolor luminescence on hierarchical self-assemblies.

Facile tuning of photophysical properties is highly desirable for boosting the performance and versatility of photoluminescent materials. In an attempt to overcome the challenge of achieving the photoswitching of multicolor luminescence on unimolecular platforms, we here report a novel hierarchical self-assembly of a cyanostilbene-naphthalimide dyad as the realization of phototunable luminescence at the unimolecular level. The work takes advantage of the photoisomerization of the cyanostilbene moiety from the Z form to its E form, which causes a morphological disorder in the molecular self-assembly and gives rise to a dual fluorescent characteristic accompanied by a progressive luminescent color conversion from yellow to green and finally to blue. Such systems with convertible multicolor luminescence might exhibit application potentials for unimolecular selective imaging and labeling, as exemplified by the cell imaging studies presented in this work.

Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity

In this study, a type of intracellular redox-triggered hollow mesoporous silica nanoreservoirs (HMSNs) with tumor specificity was developed in order to deliver anticancer drug (i.e., doxorubicin (DOX)) to the target tumor cells with high therapeutic efficiency and reduced side effects. Firstly, adamantanamine was grafted onto the orifices of HMSNs using a redox-cleavable disulfide bond as an intermediate linker. Subsequently, a synthetic functional molecule, lactobionic acid-grafted-β-cyclodextrin (β-CD-LA), was immobilized on the surface of HMSNs through specific complexation with the adamantyl group, where β-CD served as an end-capper to keep the loaded drug within HMSNs. β-CD-LA on HMSNs could also act as a targeting agent towards tumor cells (i.e., HepG2 cells), since the lactose group in β-CD-LA is a specific ligand binding with the asialoglycoprotein receptor (ASGP-R) on HepG2 cells. Inxa0vitro studies demonstrated that DOX-loaded nanoreservoirs could be selectively endocytosed by HepG2 cells, releasing therapeutic DOX into cytoplasm and efficiently inducing the apoptosis and cell death. Inxa0vivo investigations further confirmed that DOX-loaded nanoreservoirs could permeate into the tumor sites and actively interact with tumor cells, which inhibited the tumor growth with the minimized side effect. On the whole, this drug delivery system exhibits a great potential as an efficient carrier for targeted tumor therapy inxa0vitro and inxa0vivo.

Graphene oxide wrapped gold nanoparticles for intracellular Raman imaging and drug delivery

Graphene oxide wrapped gold nanoparticles (Au@NGO) were fabricated by a one-step synthesis. The surface enhanced Raman scattering (SERS) signal from Au@NGO was employed for intracellular Raman imaging in HeLa cancer cells. Anticancer drug doxorubicin was attached onto the nanoparticle surface through noncovalent interactions, and was delivered into HeLa cells for chemotherapy.

Hydrazone-Bearing PMMA-Functionalized Magnetic Nanocubes as pH-Responsive Drug Carriers for Remotely Targeted Cancer Therapy in Vitro and in Vivo

To develop vehicles for efficient chemotherapeutic cancer therapy, we report a remotely triggered drug delivery system based on magnetic nanocubes. The synthesized magnetic nanocubes with average edge length of around 30 nm acted as cores, whereas poly(methyl methacrylate) (PMMA) was employed as an intermediate coating layer. Hydrazide was then tailored onto PMMA both for doxorubicin (DOX) loading and pH responsive drug delivery via the breakage of hydrazine bonds. The successful fabrication of the pH responsive drug carrier was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and magnetic hysteresis loops, respectively. The carrier was stable at neutral environment and doxorubicin released at pH of 5.0. Cell viability assay and confocal laser scanning microscopy observations demonstrated that the loaded DOX could be efficiently released after cellular endocytosis and induced cancer cells apoptosis thereby. More importantly, the carrier could be guided to the tumor tissue site with an external magnetic field and led to efficient tumor inhibition with low side effects, which were reflected by magnetic resonance imaging (MRI), change of tumor size, TUNEL staining, and H&E staining assays, respectively. All results suggest that hydrazide-tailoring PMMA-coated magnetic nanocube would be a promising pH-responsive drug carrier for remotely targeted cancer therapy in vitro and in vivo.

Bimetallic Metal-Organic Frameworks: Probing the Lewis Acid Site for CO2 Conversion.

A highly porous metal-organic framework (MOF) incorporating two kinds of second building units (SBUs), i.e., dimeric paddlewheel (Zn2 (COO)4 ) and tetrameric (Zn4 (O)(CO2 )6 ), is successfully assembled by the reaction of a tricarboxylate ligand with Zn(II) ion. Subsequently, single-crystal-to-single-crystal metal cation exchange using the constructed MOF is investigated, and the results show that Cu(II) and Co(II) ions can selectively be introduced into the MOF without compromising the crystallinity of the pristine framework. This metal cation-exchangeable MOF provides a useful platform for studying the metal effect on both gas adsorption and catalytic activity of the resulted MOFs. While the gas adsorption experiments reveal that Cu(II) and Co(II) exchanged samples exhibit comparable CO2 adsorption capability to the pristine Zn(II) -based MOF under the same conditions, catalytic investigations for the cycloaddition reaction of CO2 with epoxides into related carbonates demonstrate that Zn(II) -based MOF affords the highest catalytic activity as compared with Cu(II) and Co(II) exchanged ones. Molecular dynamic simulations are carried out to further confirm the catalytic performance of these constructed MOFs on chemical fixation of CO2 to carbonates. This research sheds light on how metal exchange can influence intrinsic properties of MOFs.

In Situ Integration of Anisotropic SnO2 Heterostructures inside Three-Dimensional Graphene Aerogel for Enhanced Lithium Storage

Three-dimensional (3D) graphene aerogel (GA) has emerged as an outstanding support for metal oxides to enhance the overall energy-storage performance of the resulting hybrid materials. In the current stage of the studies, metals/metal oxides inside GA are in uncrafted geometries. Introducing structure-controlled metal oxides into GA may further push electrochemical properties of metal oxide-GA hybrids. Using rutile SnO2 as an example, we demonstrated here a facile hydrothermal strategy combined with a preconditioning technique named vacuum-assisted impregnation for in situ construction of controlled anisotropic SnO2 heterostructures inside GA. The obtained hybrid material was fully characterized in detail, and its formation mechanism was investigated by monitoring the phase-transformation process. Rational integration of the two advanced structures, anisotropic SnO2 and 3D GA, synergistically led to enhanced lithium-storage properties (1176 mAh/g for the first cycle and 872 mAh/g for the 50th cycle at 100 mA/g) as compared with its two counterparts, namely, rough nanoparticles@3D GA and anisotropic SnO2@2D graphene sheets (618 and 751 mAh/g for the 50th cycle at 100 mA/g, respectively). It was also well-demonstrated that this hybrid material was capable of delivering high specific capacity at rapid charge/discharge cycles (1044 mAh/g at 100 mA/g, 847 mAh/g at 200 mA/g, 698 mAh/g at 500 mA/g, and 584 mAh/g at 1000 mA/g). The in situ integration strategy along with vacuum-assisted impregnation technique presented here shows great potential as a versatile tool for accessing a variety of sophisticated smart structures in the form of anisotropic metals/metal oxides within 3D GA toward useful applications.