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Chronic heart failure is often characterized by the elevated amounts of reactive oxygen species such as hydrogen peroxide (H 2 O 2 ) in the heart. Thus, it is of importance that selective release of therapeutic drugs occurs at the heart failure site to maximize therapeutic effects. In this work, functional mesoporous silica nanoparticles (MSNPs) were developed for detection of H 2 O 2 , selective drug release and controlled treatment toward heart failure. The H 2 O 2 -sensitive probe was attached to the surface of the MSNPs, and a therapeutic drug of heart failure, captopril, was loaded within the pores of the MSNPs and retained by the binding of α-cyclodextrin to the probe. H 2 O 2 present in tissue could react with the probe and enable the dissociation of α-cyclodextrin present on the nanoparticle surface, so that captopril could be successfully released along with "turn-on" of the probe fluorescence. In vivo experiments using the KillerRed heart failure transgenic zebrafish model demonstrated that this therapeutic system is physiologically responsive. Captopril-loaded MSNPs showed high therapeutic efficacy, improving the heartbeat rate and cardiac output in zebrafish experiencing acute KillerRed-induced heart failure.

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX-loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX-loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, polymeric prodrug coated hollow mesoporous silica nanoparticles (HMSNs) with encapsulated near-infrared (NIR) absorbing dye were prepared and explored for combined photothermal-chemotherapy. A copolymer integrated with tert-butoxycarbonyl protected hydrazide groups and oligoethylene glycols was initially grafted on the surface of HMSNs via reversible addition-fragmentation chain-transfer (RAFT) polymerization followed by the deprotection to reactivate the hydrazide groups for the conjugation of anticancer drug doxorubicin (DOX). DOX was covalently bound onto the polymer substrate by acid-labile hydrazone bond and released quickly in weak acidic environment for chemotherapy. The hollow cavity of HMSNs was loaded with an NIR absorbing dye IR825 to form the final multifunctional hybrid denoted as HMSNs-DOX/IR825. The hybrid exhibited good dispersity and stability as well as high light-to-heat conversion efficiency. As revealed by confocal microscopy and flow cytometry analysis, the hybrid was efficiently taken up by cancer cells, and the conjugated DOX could be released under the cellular environment. In vitro cytotoxicity study demonstrated that anticancer activity of HMSNs-DOX/IR825 could be significantly improved by the NIR irradiation, which led to a satisfactory therapeutic efficacy through the combination treatment. Thus, the developed hybrid could be a promising candidate for the combined photothermal-chemotherapy of cancer.

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.

A "turn-on" thiol-responsive fluorescence probe was synthesized and integrated into polymeric nanoparticles for sensing intracellular thiols. There is a photo-induced electron transfer process in the off state of the probe, and this process is terminated upon the reaction with thiol compounds. Configuration interaction singles (CIS) calculation was performed to confirm the mechanism of this process. A series of sensing studies were carried out, showing that the probe-integrated nanoparticles were highly selective towards biological thiol compounds over non-thiolated amino acids. Kinetic studies were also performed to investigate the relative reaction rate between the probe and the thiolated amino acids. Subsequently, the Gibbs free energy of the reactions was explored by means of the electrochemical method. Finally, the detection system was employed for sensing intracellular thiols in cancer cells, and the sensing selectivity could be further enhanced with the use of a cancer cell-targeting ligand in the nanoparticles. This development paves a path for the sensing and detection of biological thiols, serving as a potential diagnostic tool in the future.

Mesoporous silica nanoparticles (MSNPs) have been widely used as drug carriers for stimuli-responsive drug delivery. Herein, a catalysis screening technique was adopted for analyzing the effects of chain length, terminal group, and density of disulfide-appended functional ligands on the surface of MSNPs on drug-loading capacity and glutathione-triggered drug-release kinetics. The ligand with an intermediate length (5 carbon atoms) and a bulky terminal group (cyclohexyl) that complexes with theβ-cyclodextrin ring showed the highest drug loading capacity as well as good release kinetics. In addition, decreasing the surface coverage of the functional ligands led to an enhancement in drug release. In vitro drug-delivery experiments on a melanoma cell line (B16-F10) by using the functionalized MSNPs further supported the conclusion. The results obtained may serve as a general guide for developing more effective MSNP systems for drug delivery., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cancer is currently one of the major diseases that has gained a lot of scientific attention. Conventional cancer therapeutics involve surgical removal of tumors from patients followed by chemotherapeutic treatment. In the use of anticancer drugs during the chemotherapy process, patients often suffer from a variety of undesirable side effects including damage to normal organs. Thus, there is an urgent need for the development of novel strategies to overcome these side effect issues. Among several strategies, the utilization of nanocarriers for anticancer drug delivery has shown improved therapeutic efficiency of the drugs with minimization of the undesirable side effects. In this review, we discuss various types of nanocarriers recently reported in the literature for application in cancer therapy. We introduce some targeting ligands that have been functionalized on nanocarriers in order to impart specificity to the nanocarriers for targeted drug delivery. We also highlight some therapeutic cargoes that are commonly used and their therapeutic mechanisms in cancer treatment. Finally, we summarize some interesting stimulus strategies for controlled release of therapeutic cargoes at tumor sites. This review is expected to inspire new ideas and create novel strategies in advancing efficient cancer therapy using nanomedicine approaches.

Glutamate receptor antagonists have been known to play a crucial role in the treatment of many neuronal diseases. Recently, these antagonists have also shown therapeutic effects in the treatment of cancer. In this study, an ionotropic glutamate (iGlu) receptor antagonist, 4-hydroxyphenylacetyl spermine ( L1), was used concurrently with a common anticancer drug, doxorubicin (Dox), for simultaneous cancer therapy. Mesoporous silica nanoparticles (MSNPs) were employed as the delivery vehicle for both L1 and Dox by conjugating the iGlu receptor antagonist on the surface and encapsulating Dox within the mesopores. Dox was then trapped within the mesopores by functionalizing a redox-cleavable capping group on the MSNP surface, and it could be released upon exposure to the reductive glutathione. In vitro studies on B16F10 and NIH3T3 cell lines revealed that the iGlu receptor antagonist L1 exhibited therapeutic as well as targeting effects. In addition, the simultaneous use of therapeutic L1 and Dox proved to be synergistic in the treatment of cancer. The present work demonstrated the feasibility of employing a delivery system to deliver both neuroprotective drug and anticancer drug for efficient anticancer treatment. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNPs) have been widely used as drug carriers for stimuli-responsive drug delivery. Herein, a catalysis screening technique was adopted for analyzing the effects of chain length, terminal group, and density of disulfide-appended functional ligands on the surface of MSNPs on drug-loading capacity and glutathione-triggered drug-release kinetics. The ligand with an intermediate length (5 carbon atoms) and a bulky terminal group (cyclohexyl) that complexes with theβ-cyclodextrin ring showed the highest drug loading capacity as well as good release kinetics. In addition, decreasing the surface coverage of the functional ligands led to an enhancement in drug release. In vitro drug-delivery experiments on a melanoma cell line (B16-F10) by using the functionalized MSNPs further supported the conclusion. The results obtained may serve as a general guide for developing more effective MSNP systems for drug delivery. [ABSTRACT FROM AUTHOR]

A combination therapy using a neuroprotective drug, N ‐ (4 ‐ hydroxylphenylacetyl) spermine, and an anticancer drug, doxorubicin, integrated with functional mesoporous silica nanoparticles as carriers has been developed for improved treatment of metastatic melanoma cancer, as reported by Y. Zhao et al. in their Full Paper on page 6123 ff. [ABSTRACT FROM AUTHOR]