A comparison of mesoporous silica nanoparticles and mesoporous organosilica nanoparticles as drug vehicles for cancer therapy.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for use in cancer treatment owing to their excellent biocompatibility and drug-loading capacity. However, MSN's incomplete drug release and toxic bioaccumulation phenomena limit their clinical application. Recently, researchers have presented redox responsive mesoporous organosilica nanoparticles containing disulfide (S-S) bridges (ss-MONs). These nanoparticles retained their ability to undergo structural degradation and increased their local release activity when exposed to reducing agents. Disulfide-based mesoporous organosilica nanoparticles offer researchers a better option for loading chemotherapeutic drugs due to their effective biodegradability through the reduction of glutathione. Although the potential of ss-MONs in cancer theranostics has been studied, few researchers have systematically compared ss-MONs with MSNs with regard to endocytosis, drug release, cytotoxicity, and therapeutic effect. In this work, ss-MONs and MSNs with equal morphology and size were designed and used to payload doxorubicin hydrochloride (DOX) for liver cancer chemotherapy. The ss-MONs showed considerable degradability in the presence of glutathione and performed comparably to MSNs on biocompatibility measures, including cytotoxicity and endocytosis, as well as in drug-loading capacity. Notably, DOX-loaded ss-MONs exhibited higher intracellular drug release in cancer cells and better anticancer effects in comparison with DOX-loaded MSNs. Hence, the ss-MONs may be more desirable carriers for a highly efficient and safe treatment of cancer.

Yue J ，Luo SZ ，Lu MM ，Shao D ，Wang Z ，Dong WF ... -  《-》

Multifunctional mesoporous silica nanoparticles modified with tumor-shedable hyaluronic acid as carriers for doxorubicin.

In this paper, a CD44-targeted and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) was synthesized by conjugating tumor-shedable hyaluronic acid (HA) on the surface of MSNs via disulfide bonds. Doxorubicin hydrochloride (DOX·HCl) was physically encapsulated into HA modified MSNs (MSNs/SS/HA@DOX) as a model drug. MSNs/SS/HA@DOX (40nm) had a high drug loading (14.1%) and redox-responsive drug release property. The cellular uptake behaviors of MSNs/SS/HA@DOX by HeLa and LO2 cells were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). MSNs/SS/HA@DOX exhibited higher cellular uptake efficacy via CD44-mediated endocytosis by HeLa cells (CD44 over-expressed cells) than by LO2 cells (CD44 deficient cells). The in vitro cytotoxicity assay demonstrated that MSNs/SS/HA@DOX exhibited higher cytotoxicity to HeLa cells than to LO2 cells. These results indicated that MSNs/SS/HA@DOX might be promising as a multifunctional drug delivery system to improve the anti-tumor efficacy of chemotherapeutic drugs.

Zhang J ，Sun Y ，Tian B ，Li K ，Wang L ，Liang Y ，Han J ... -  《-》

Ultrasmall mesoporous organosilica nanoparticles: Morphology modulations and redox-responsive biodegradability for tumor-specific drug delivery.

Beyond mesoporous silica nanoparticles (MSNs), mesoporous organosilica nanoparticles (MONs) have been becoming an even more attractive alternative to the traditional organic or inorganic nanomaterials in biomedical applications, especially for drug delivery, due to its high surface area, stable physicochemical properties, low toxicity, high biocompatibility, and particularly the devisable features decided by the incorporated organic fragments. However, it is still challenging to fabricate uniform ultrasmall MONs with tunable composition, morphology and fine biodegradability. Herein, we report, on the large-scale fabrication of monodispersed and molecularly organic-inorganic hybrid MONs with framework-incorporated physiologically active thioether bonds, controllable nanostructure, composition and morphology, which provides the material foundation for exploring the versatile biomedical applications of organosilica nanosystems. The hybrid MONs of less than 50 nm in particle size exhibit the unique reduction-responsive biodegradation behavior, and the biodegradation rate is significantly higher than that of traditional mesoporous silica nanoparticles with pure inorganic SiOSi framework. The reductive microenvironment-triggered biodegradation of MONs induces the concurrent reduction-responsive anticancer drug releasing from MONs, enabling tumor-specific drug delivery. Importantly, these biocompatible and biodegradable MONs exhibit significantly improved drug-delivery efficiency and enhanced tumor-suppressing effect for combating cancer. Based on the facile and large-scale fabrication of MONs with controllable key structure/composition/morphology parameters, unique tumor microenvironment-responsive biodegradation behavior and high performance for drug delivery, the MONs therefore show more promising potentials for clinical translation as compared to traditional MSNs.

Yu L ，Chen Y ，Lin H ，Du W ，Chen H ，Shi J ... -  《-》

Functionalization of mesoporous organosilica nanocarrier for pH/glutathione dual-responsive drug delivery and imaging of cancer therapy process.

A multifunctional drug nanocarrier is developed by incorporating acetaldehyde-modified-cystine (AMC) into mesoporous organosilica nanoparticles (MONs), shortly termed as MONs-AMC. The anticancer drug doxorubicin (DOX) links directly to MONs-AMC through electrostatic interaction between DOX and AMC to produce a conjugate, MONs-AMC-DOX, with a drug loading efficiency of 26.24 ± 1.35%, corresponding to a loading capacity of 0.26 ± 0.01mgmg-1 for DOX. Schiff base AMC contains a -S-S- bond and two -C˭N- bonds which cleave in the presence of certain level of GSH and in an acidic medium, providing MONs-AMC-DOX the capability for triggering pH and glutathione (GSH) dual-responsive drug release. Further, the self-fluorescent nature of AMC offers the tracing capability without the need of fluorescent label, which facilitates real-time tracing of the drug delivery and cancer therapy process. With 10mmolL-1 GSH and at pH 5.0, a drug release efficiency of 52.27 ± 2.84% is achieved. The intracellular drug release process is traced with confocal laser scanning microscope by monitoring the green fluorescence of MONs-AMC-DOX and red fluorescence of DOX with excitation at 408nm and 488nm, respectively. The drug loaded nanocarriers exhibit a time-dependent cellular uptake behavior, providing an enhanced therapeutic effect to A549 cancer cells.

Hu LL ，Meng J ，Zhang DD ，Chen ML ，Shu Y ，Wang JH ... -  《-》

Facile synthesis of organosilica-capped mesoporous silica nanocarriers with selective redox-triggered drug release properties for safe tumor chemotherapy.

Shen L ，Pan S ，Niu D ，He J ，Jia X ，Hao J ，Gu J ，Zhao W ，Li P ，Li Y ... -  《-》