Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Chitosan‐Capped Mesoporous Silica Nanoparticles as pH‐Responsive Nanocarriers for Controlled Drug Release

Herein, we present a straightforward synthesis of pH‐responsive chitosan‐capped mesoporous silica nanoparticles (MSNs). These MCM‐41‐type MSNs could be used as nanocapsules to accommodate guest molecules. Subsequently, (3‐glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs, which served as a bridge to link between MSNs and chitosan, which is ubiquitous in nature and commercially available. Owing to the pH‐responsive and biocompatible features of chitosan, the loading and release of an anti‐cancer drug, doxorubicin hydrochloride, were carried out in vitro, in which the composite chitosan‐capped MSNs (CS‐MSNs) showed excellent environmental response. As the pH value of the media decreased, the degree of drug release correspondingly increased. Moreover, thanks to the perfect biocompatibility of chitosan, the CS‐MSNs exhibited lower cytotoxicity than that of the naked MSNs in an MTT assay. In addition, the in vitro kill potency against MCF‐7 breast‐cancer cells was enhanced over time, as well as with increasing concentration of the drug‐loaded CS‐MSNs. These results indicate that CS‐MSNs are promising candidates for pH‐responsive drug delivery in cancer therapy.     

Lipid,protein and poly(NIPAM) coated mesoporous silica nanoparticles for biomedical applications

In the past decade, mesoporous silica nanoparticles (MSNs) as nanocarriers have showed much potential in advanced nanomaterials due to their large surface area and pore volume. Especially, more and more MSNs based nanodevices have been designed as efficient drug delivery systems (DDSs) or biosensors. In this paper, lipid, protein and poly(NIPAM) coated MSNs are reviewed from the preparation, properties and their potential application. We also introduce the preparative methods including physical adsorption, covalent binding and self-assembly on the MSNs' surfaces. Furthermore, the interaction between the aimed cells and these molecular modified MSNs is discussed. We also demonstrate their typical applications, such as photodynamic therapy, bioimaging, controlled release and selective recognition in biomedical field.     

New advances in gated materials of mesoporous silica for drug controlled release

Drug delivery systems (DDS) are used to deliver therapeutic drugs to improve selectivity and reduce side effects. With the development of nanotechnology, many nanocarriers have been developed and applied to drug delivery, including mesoporous silica. Mesoporous silica nanoparticles (MSNs) have attracted a lot of attention for simple synthesis, biocompatibility, high surface area and pore volume. Based on the pore system and surface modification, gated mesoporous silica nanoparticles can be designed to realize on-command drug release, which provides a new approach for selective delivery of antitumor drugs. Herein, this review mainly focuses on the “gate keepers” of mesoporous silica for drug controlled release in nearly few years (2017–2020). We summarize the mechanism of drug controlled release in gated MSNs and different gated materials: inorganic gated materials, organic gated materials, self-gated drug molecules, and biological membranes. The facing challenges and future prospects of gated MSNs are discussed rationally in the end.     

Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles

Most present nanodrug delivery systems have been developed to target cancer cells but rarely nuclei. However, nuclear-targeted drug delivery is expected to kill cancer cells more directly and efficiently. In this work, TAT peptide has been employed to conjugate onto mesoporous silica nanoparticles (MSNs-TAT) with high payload for nuclear-targeted drug delivery for the first time. Monodispersed MSNs-TAT of varied particle sizes have been synthesized to investigate the effects of particle size and TAT conjugation on the nuclear membrane penetrability of MSNs. MSNs-TAT with a diameter of 50 nm or smaller can efficiently target the nucleus and deliver the active anticancer drug doxorubicin (DOX) into the targeted nucleus, killing these cancer cells with much enhanced efficiencies. This study may provide an effective strategy for the design and development of cell-nuclear-targeted drug delivery.     

General one-pot strategy to prepare multifunctional nanocomposites with hydrophilic colloidal nanoparticles core/mesoporous silica shell structure

A general and facile strategy was developed to coat hydrophilic inorganic nanoparticles directly with mesoporous silica nanoparticles (MSNs). The cationic surfactant of cetyltrimethylammonium bromide (CTAB) was adsorbed to various negatively charged CdTe quantum dots, Fe(3)O(4) nanocrystals or Au nanoparticles, introducing the bilayer of CTAB overcoating with positive charge. The subsequent sol-gel reaction of TEOS with the basic catalyst resulted in uniform nanocomposites. The concentration of CTAB and NH(4)OH in the recipe strongly influenced the number of inorganic nanoparticles in the nanocomposites and the homogeneity of MSNs shell. One dimensional Au nanorods and larger size of solid SiO(2) nanoparticles were also able to coat with MSNs using a similar synthetic procedure. The proposed method was greatly simplified without the help of any mediators or silane coupling agents and excellent mesostructural performance was readily achieved. Compared to the methods known from the literatures for the coating of hydrophobic nanoparticles, this efficient way is especially useful for trapping different hydrophilic nanoparticles with arbitrary sizes and shapes into MSNs. These highly versatile multifunctional nanocomposites, together with the pH-responsible drug release behaviors, non-toxicity to normal cells and ease of uptake into cancer cells, are expected to be utilized as drug delivery system for simultaneous imaging and therapeutic applications.     

由聚合物门控的介孔二氧化硅基刺激响应性药物递送系统

本文主要介绍了以聚合物体系作为门控构筑的基于介孔二氧化硅纳米粒子的刺激响应性药物控释体系,并根据聚合物类别将门控体系分为聚合物刷、聚合物交联网络和聚合物包裹层三类.根据聚合物"阀门"与无机纳米粒子的共价或非共价连接方式,综述了这些杂化材料在不同外界刺激作用下的药物控制释放行为,并给出该领域所面临的机遇和挑战.     

pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids

Acid-decomposable, luminescent ZnO quantum dots (QDs) have been employed to seal the nanopores of mesoporous silica nanoparticles (MSNs) in order to inhibit premature drug (doxorubicin) release. After internalization into HeLa cells, the ZnO QD lids are rapidly dissolved in the acidic intracellular compartments, and as a result, the loaded drug is released into the cytosol from the MSNs. The ZnO QDs behave as a dual-purpose entity that not only acts as a lid but also has a synergistic antitumor effect on cancer cells. We anticipate that these nanoparticles may prove to be a significant step toward the development of a pH-sensitive drug delivery system that minimizes drug toxicity.     

Functionalized mesoporous silica nanoparticles templated by pyridinium ionic liquid for hydrophilic and hydrophobic drug release application

Chemotherapy is the most common treatment for all cancer patients but this treatment poses many side effects due to lack of drug’s selectivity. To overcome this problem, utilizing a better and more effective delivery agent is the solution. Mesoporous silica nanoparticles (MSNs) emerged as a promising platform in development of drug delivery agent. This is due to its desirable properties such as tunable pores, large surface area, good biocompatibility and easy functionalization. Furthermore, these properties can be tuned through the utilization of alternative template such as pyridinium ionic liquid. Besides, by employing surface functionalization, the effectiveness of MSNs as drug delivery agent may also increase. This work reported the usage of 1-hexadecylpyridinium bromide ionic liquid as template for MSNs production and the surface of MSNs was then further functionalized via post – grafting method in order to obtain MSN – NH₂, MSN – SH and MSN – COOH as drug carrier, respectively. These functionalized MSNs were then used to study the drug loading and drug release of hydrophilic drug, gemcitabine and hydrophobic drug, quercetin. For quercetin, MSN-NH₂ had the highest drug loading percentage (72%) and slowest release (14%) in 48 h while for gemcitabine, it was found that MSN-COOH had the highest drug loading percentage (45%) and slowest release (15%) in 48 h. Based on the results, it is suggested that mesoporous silica nanoparticle with surface functionalization has suitable properties for controlled drug release which gives constant release behavior over a period of time to avoid repeated administration of drug where the drug is administered at a fixed dosage and regular time interval.     

Chemical Design of Nuclear‐Targeting Mesoporous Silica Nanoparticles for Intra‐nuclear Drug Delivery

Targeted drug delivery has been widely explored for efficient tumor therapy with desired efficacy but minimized side effects. It is widely known that large numbers of DNA‐toxins, such as doxorubicin, genes, reactive oxygen species, serving as therapeutic agents, can result in maximized therapeutic effects via the interaction directly with DNA helix. So after cellular uptake, these agents should be further delivered into cell nuclei to play their essential roles in damaging the DNA helix in cancer cells. Here, we demonstrate the first paradigm established in our laboratory in developing nuclear‐targeted drug delivery systems (DDSs) based on MSNs for enhanced therapeutic efficiency in the hope of speeding their translation into the clinics. Firstly, nuclear‐targeting DDSs based on MSNs, capable of intranuclear accumulation and drug release therein, were designed and constructed for the first time, resulting in much enhanced anticancer effects both in vitro and in vivo. Such an MSNs‐based and nuclear‐targeted drug/agent delivery strategy was further applied to overcome multidrug resistance (MDR) of malignant tumors, intra‐nuclearly deliver therapeutic genes, photosensitizers, radio‐enhancement agents and photothermal agents to realize efficient gene therapy, photodynamic therapy, radiation therapy and photothermal therapy, respectively.     

Concept Design,Development and Preliminary Physical and Chemical Characterization of Tamoxifen-Guided-Mesoporous Silica Nanoparticles

Conventional chemotherapies used for breast cancer (BC) treatment are non-selective, attacking both healthy and cancerous cells. Therefore, new technologies that enhance drug efficacy and ameliorate the off-target toxic effects exhibited by currently used anticancer drugs are urgently needed. Here we report the design and synthesis of novel mesoporous silica nanoparticles (MSNs) equipped with the hormonal drug tamoxifen (TAM) to facilitate guidance towards estrogen receptors (ERs) which are upregulated in breast tumours. TAM is linked to the MSNs using a poly-ʟ-histidine (PLH) polymer as a pH-sensitive gatekeeper, to ensure efficient delivery of encapsulated materials within the pores. XRD, HR-TEM, DLS, SEM, FT-IR and BET techniques were used to confirm the successful fabrication of MSNs. The MSNs have a high surface area (>1000 m²/g); and a mean particle size of 150 nm, which is an appropriate size to allow the penetration of premature blood vessels surrounding breast tumours. Successful surface functionalization was supported by FT-IR, XPS and TGA techniques, with a grafting ratio of approximately 29%. The outcomes of this preliminary work could be used as practical building blocks towards future formulations.     

Photosensitizer-Mesoporous Silica Nanoparticles Combination for Enhanced Photodynamic Therapy†

Mesoporous silica nanoparticles (MSNs) are widely known for their versatile applications. One of the most extended is as drug delivery systems for the treatment of cancer and other diseases. This review compiles the most representative examples in the last years of functionalized MSNs as photosensitizer carriers for photodynamic therapy (PDT) against cancer. Several commercially available photosensitizers (PSs) demonstrated poor solubility in an aqueous medium and insufficient selectivity for cancer tissues. The tumor specificity of PSs is a key factor for enhancing the PDT effect and at the same time reducing side effects. The use of nanoparticles and particularly MSNs, in which PS is covalently anchored or physically embedded, can overcome these limitations. For that, PS-MSNs can be externally decorated with compounds of interest in order to act as an active target for certain cancer cells, demonstrating enhanced phototoxicity in vitro and in vivo. The objective of this review is to collect and compare different nanosystems based on PS-MSNs pointing out their advantages in PDT against diverse types of cancers.     

P(VPBA-DMAEA) as a pH-sensitive nanovalve for mesoporous silica nanoparticles based controlled release

A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles(MSNs) functionalized on the pore outlets with poly(4-vinylphenybronic acid-co-2-(dimethylamino)ethyl acrylate) [P(VPBA-DMAEA)]. Four kinds of P(VPBA-DMAEA)-gated MSNs were synthesized and applied for the p H-sensitive controlled release. The results showed that P(VPBADMAEA) can work as a p H-sensitive nanovalve. The release behavior of the hybrid nanoparticles could be adjusted by changing the mole ratio of VPBA and DMAEA. With the increasing of the mole ratio of VPBA,the leakage of the entrapped molecules in the pores of MSNs could be decreased at neutral and alkaline conditions. By altering the p H of buffer from 4.0 to 8.0, the valve could be switched ‘‘on' and ‘‘off'reversibly. In addition, cells viability results indicated that these P(VPBA-DMAEA)-gated MSNs had good biocompatibility. We believe that these MSNs based p H-sensitive controlled release system will provide a promising nanodevice for sited release of drug delivery.     

Cell‐Penetrating Poly(disulfide) Assisted Intracellular Delivery of Mesoporous Silica Nanoparticles for Inhibition of miR‐21 Function and Detection of Subsequent Therapeutic Effects

The design of drug delivery systems capable of minimal endolysosomal trapping, controlled drug release, and real‐time monitoring of drug effect is highly desirable for personalized medicine. Herein, by using mesoporous silica nanoparticles (MSNs) coated with cell‐penetrating poly(disulfide)s and a fluorogenic apoptosis‐detecting peptide (DEVD‐AAN), we have developed a platform that could be uptaken rapidly by mammalian cells via endocytosis‐independent pathways. Subsequent loading of these MSNs with small molecule inhibitors and antisense oligonucleotides resulted in intracellular release of these drugs, leading to combination inhibition of endogenous miR‐21 activities which was immediately detectable by the MSN surface‐coated peptide using two‐photon fluorescence microscopy.     

Single‐Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR‐122 Function in Hepatocellular Carcinoma Cells by using “Smart” Mesoporous Silica Nanoparticles

MicroRNAs (miRNAs) regulate a variety of biological processes. The liver‐specific, highly abundant miR‐122 is implicated in many human diseases including cancer. Its inhibition has been found to result in a dramatic loss in the ability of Hepatitis C virus (HCV) to infect host cells. Both antisense technology and small molecules have been used to independently inhibit endogenous miR‐122 function, but not in combination. Intracellular stability, efficient delivery, hydrophobicity, and controlled release are some of the current challenges associated with these novel therapeutic methods. Reported herein is the first single‐vehicular system, based on mesoporous silica nanoparticles (MSNs), for simultaneous cellular delivery of miR‐122 antagomir and small molecule inhibitors. The controlled release of both types of inhibitors depends on the expression levels of endogenous miR‐122, thus enabling these drug‐loaded MSNs to achieve combination inhibition of its targeted mRNAs in Huh7 cells.     

Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In Vitro and In Vivo

Mesoporous silica-based nanoparticles are generally accepted as a potential platform for drug loading with a lot of advantages, except for their complex purification procedures and structures that are difficult to decompose. In this work, biocompatible hyperbranched polyglycerol is introduced to synthesize mesoporous silica nanoparticles (MSNs). The materials possess good biocompatibility, controlled release, and biodegradability. They also show passive targeting capability through the enhanced permeability and retention effect and can be excreted from the biological system. The method avoids the needs to employ traditional surfactants and complicated purified procedures, which make these MSNs an efficient delivery system for cancer therapy.     

Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy

A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation.     

Dual pH and glucose sensitive gel gated mesoporous silica nanoparticles for drug delivery

A low-molecular-weight gel with dual pH and glucose sensitivity was designed as the gate controller for mesoporous silica nanoparticles (MSNs) to fabricate a smart drug delivery system. The smart gel caped MSNs could control the antidiabetic drug release via the detection of glucose and pH levels.     

Mesoporous silica nanoparticles-assisted ruthenium(Ⅱ) complexes for live cell staining

Ruthenium complexes which can bind to DNA via electrostatic and intercalation interactions producing strong luminescence have become ideal candidates for DNA staining. However, some of them such as Ru(phen)_3Cl_2 and Ru(phen)_2(dppz)Cl_2 could hardly cross the cellular membrane of live cells which limited their further interaction with DNA in live cells. To solve this problem, a potential approach is to find a proper vehicle for loading and delivery of these ruthenium complexes into live cells.Mesoporous silica nanoparticles(MSNs) with non-toxicity and good biocompatibility can be good candidates. More importantly,ruthenium complexes with positively charge could be loaded on negatively charged MSNs via electrostatic attractions to form MSNs-Ru hybrid. In vitro test demonstrated that MSNs had no side effects on the interactions between Ru complexes and DNA.Furthermore, it is found that the MSNs-Ru hybrid can enter into living human cervical cancer cells HeLa and stain the DNA while the corresponding ruthenium complexes alone could hardly cross the cellular membrane in the control experiment, demonstrating MSNs can be employed to be an efficient ruthenium complexes delivery nanomaterial for live cell staining.     

Effect of mesopores on solidification of sirolimus self-microemulsifying drug delivery system

The mesoporous silica materials had a high loading efficiency of sirolimus-SMEDDS. The length of the mesopores played a more important role than the pore diameter in drug dissolution and in vivo absorption.