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 ... -  《-》

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 ... -  《-》

Controllable synthesis of versatile mesoporous organosilica nanoparticles as precision cancer theranostics.

Despite the advantages of mesoporous silica nanoparticles (MSNs) in drug delivery, the inherent non-biodegradability seriously impedes the clinical translation of inorganic MSNs, so the current research focus has been turned to mesoporous organosilica nanoparticles (MONs) with higher biocompatibility and easier biodegradability. Recent remarkable advances in silica fabrication chemistry have catalyzed the emergence of a library of MONs with various structures and functions. This review will summarize the latest state-of-the-art studies on the precise control of morphology, structure, framework, particle size and pore size of MONs, which enables the precise synthesis of MONs with suitable engineering for precision stimuli-responsive drug delivery/release, bioimaging and synergistic therapy. Besides, the potential challenges about the future development of MONs are also outlooked with the intention of attracting more researchers to promote the clinical translation of MONs.

Cheng Y ，Jiao X ，Fan W ，Yang Z ，Wen Y ，Chen X ... -  《-》

Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality.

Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a "chemical homology" mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50 nm particle dimension were constructed in mass production. A physiologically active disulfide bond (SS) was directly incorporated into the silica framework, which could break up upon contacting the reducing microenvironment of tumor tissue and biodegrade accordingly. Such a tumor-specific biodegradability is also responsible for the tumor-responsive drug releasing by the fast biodegradation and disintegration of the framework. The ultrasmall particle size of HMONs guarantees their high accumulation into tumor tissue, thus causing the high chemotherapeutic outcome. This research provides a paradigm that framework organic-inorganic hybridization can endow the inorganic nanocarrier with unique biological effects suitable for biomedical application, benefiting the development of novel nanosystems with the unique bio-functionality and performance.

Huang P ，Chen Y ，Lin H ，Yu L ，Zhang L ，Wang L ，Zhu Y ，Shi J ... -  《-》

"Manganese Extraction" Strategy Enables Tumor-Sensitive Biodegradability and Theranostics of Nanoparticles.

Yu L ，Chen Y ，Wu M ，Cai X ，Yao H ，Zhang L ，Chen H ，Shi J ... -  《-》