Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

Introduction: Mesoporous silica nanoparticles (MSNs) are outstanding nanoplatforms for drug delivery. Herein, the most recent advances to turn MSN-based carriers into minimal side effect drug delivery agents are covered.

Areas covered: This review summarizes the scientific advances dealing with MSNs for targeted and stimuli-responsive drug delivery since 2015. Delivery aspects to diseased tissues together with approaches to obtain smart MSNs able to respond to internal or external stimuli and their applications are here described. Special emphasis is done on the combination of two or more stimuli on the same nanoplatform and on combined drug therapy.

Expert opinion: The use of MSNs in nanomedicine is a promising research field because they are outstanding platforms for treating different pathologies. This is possible thanks to their structural, chemical, physical and biological properties. However, there are certain issues that should be overcome to improve the suitability of MSNs for clinical applications. All materials must be properly characterized prior to their in vivo evaluation; furthermore, preclinical in vivo studies need to be standardized to demonstrate the MSNs clinical translation potential.     

Capped mesoporous silica nanoparticles as stimuli-responsive controlled release systems for intracellular drug/gene delivery

Importance of the field: The incorporation of stimuli-responsive properties into nanostructured systems has recently attracted significant attention in the research of intracellular drug/gene delivery. In particular, numerous surface-functionalized, end-capped mesoporous silica nanoparticle (MSN) materials have been designed as efficient stimuli-responsive controlled release systems with the advantageous ‘zero premature release’ property.

Areas covered in this review: Herein, the most recent research progress on the design of biocompatible, capped MSN materials for stimuli-responsive intracellular controlled release of therapeutics and genes is reviewed. A series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different cargoes are summarized. Recent investigations on the biocompatibility of MSN both in vitro and in vivo are also discussed.

What the reader will gain: The reader will gain an understanding of the challenges for the future exploration of biocompatible stimuli-responsive MSN devices.

Take home message: With a better understanding of the unique features of capped MSN and its behaviors in biological environment, these multifunctional materials will find a wide variety of applications in the field of drug/gene delivery.     

Novel advances in targeted drug delivery

Developing a new drug molecule is not only time-consuming and expensive, but also mostly a failing process. However, improving bioavailability, targetability, efficacy or safety of old drugs could be more effective way to use them in clinic. For these purposes, so many strategies including individualising drug therapy, nanoparticle-based drug delivery systems, drug conjugates, therapeutic drug monitoring, stimuli-sensitive targeted therapy are investigated intensely. Depending on the desired application or targeted site, nanoparticles can be administrated as orally, locally, topically and systemically. Currently, the Food and Drug Administration and the European Medicines Agency approved nanoparticles are mostly aimed to treat cancer. Although some of these formulations were approved by Food and Drug Administration and/or European Medicines Agency to use in clinic, most of them have fell down to pass either pre-clinical or clinical trials. To have high approval rate, failure reasons need to be better understand.     

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand–receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.     

Cell microenvironment stimuli-responsive controlled-release delivery systems based on mesoporous silica nanoparticles

To develop novel tumor cell microenvironment stimuli-responsive smart controlled-release delivery systems is one of the current common interests of materials science and clinical medicine. Meanwhile, mesoporous silica nanoparticles as a promising drug carrier have become the new area of interest in the field of biomedical application in recent years because of their unique characteristics and abilities to efficiently and specifically entrap cargo molecules. This review describes the more recent developments and achievements of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled-release systems that are able to respond to tumor cell environmental changes, such as pH, glucose, adenosine-5′-triphosphate (ATP), glutathione (GSH), and H₂O₂.     

介孔二氧化硅纳米粒的研究进展

介孔二氧化硅纳米粒(MSNs)具有良好生物相容性、有序介孔结构、比表面积大、表面易修饰性等特点,在很多生物医药领域显示出了极大的应用前景,尤其是基于MSNs的纳米药物输送体系被广泛用于各种药物的递送。主要介绍MSNs和可降解MSNs的制备,同时介绍了MSNs膜包被及官能团修饰在缓释控释药物中的应用,最后探讨了MSNs递进到中空介孔二氧化硅纳米粒(HMSNs)的更大的应用前景。     

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.     

Sugar-decorated mesoporous silica nanoparticles as delivery vehicles for the poorly soluble drug celastrol enables targeted induction of apoptosis in cancer cells

Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at significantly higher rates than normal cells. Celastrol is a traditional herbal medicine known for its anti-inflammatory and anti-cancer activities. The poor aqueous solubility and lack of target selectivity of celastrol result in low therapeutic concentration of the drug reaching subcellular compartments of the target tissue, making it an interesting candidate for nanoparticulate delivery. The goal of this study was to utilize glucose as an affinity ligand decorated on mesoporous silica nanoparticles (MSNs), with the aim of delivering these celastrol-loaded MSNs with high specificity to cancer cells and inducing minimal off-target effects in healthy cells. MSNs were thus functionalized with sugar moieties by two different routes, either by conjugation directly to the MSN surface or mediated by a hyperbranched poly(ethylene imine), PEI layer; the latter to increase the cellular uptake by providing an overall positive surface charge as well as to increase the reaction sites for sugar conjugation. The effect of surface functionalization on the target-specific efficacy of the particles was assessed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEF) as a representative for normal cells. To this end a comprehensive analysis strategy was employed, including flow cytometry, confocal microscopy, and spectrophotometry. When the apoptotic effect of celastrol was evaluated, the anti-cancer activity of celastrol was shown to be significantly enhanced when it was loaded into the specifically designed MSNs. The particles themselves did not induce any toxicity, and normal cells displayed minimal off-target effects. In summary, we show that glucose-functionalized MSNs can be used as efficient carriers for targeted celastrol delivery to achieve specific induction of apoptosis in cancer cells.     

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

 Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.     

Anti-miRNA21 and resveratrol-loaded polysaccharide-based mesoporous silica nanoparticle for synergistic activity in gastric carcinoma

Abstract

Anti-miR21 and resveratrol (RSV)-loaded mesoporous silica nanoparticles (MSNs) conjugated with hyaluronic acid (HA) were developed to enhance therapeutic efficacy in gastric carcinoma. The surface conjugation of HA, which acts as a targeting ligand to the overexpressed CD44 receptor on gastric cancer cells, was clearly identified by the presence of a greyish shell on the dark MSNs. Confocal laser-scanning microscopy and flow cytometry analysis showed higher cellular internalisation of HA/RSVmirNP compared to RSVmirNP. In vitro cytotoxicity and apoptosis assays confirmed the superior anticancer effect of the optimised formulation and synergistic effects of anti-miR21 and RSV in gastric cancer cells. Importantly, HA/RSVmirNP showed significant (p?<?.001) reductions in the tumour burden compared to the other group. Indeed, HA/RSVmirNP showed a threefold higher tumour regression effect compared to that of free RSV and a twofold tumour regression effect compared to that of RSVmirNP, indicating its anticancer efficacy. The percentage of TUNEL-positive cells was significantly higher in HA/RSVmirNP-treated cells compared to any other group, indicating that the mechanism underlying the superior anticancer efficacy of HA/RSVmirNP included apoptosis and cell necrosis. Thus, a combination of anti-miR21 and RSV in a targeted nanocarrier might be a promising drug delivery system for gastric cancer therapy.     

Drug delivery from ordered mesoporous matrices

Research interest in silica-based ordered mesoporous materials (SMMs) as drug delivery systems has grown drastically in the last few years owing to the great versatility and stability of these mesoporous matrices. This review aims to resume the work carried out in this area so far and the possible applications in biomedical technologies. The different SMMs can be designed and tailored using different chemical strategies according to the drug and clinical necessity. The available channels of SMMs that can be used to store drugs can be opened and closed by different systems, in the so-called stimuli-responsive release devices. These systems could improve the therapeutic efficacy compared with conventional sustained release systems. SMMs offer such a great versatility that can be used both for oral and for local drug delivery, with huge possible applications in different clinical areas.     

Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics

Introduction: For many years, the controlled delivery of therapeutic compounds has been a matter of great interest in the field of nanomedicine. Among the wide amount of drug nanocarriers, magnetic iron oxide nanoparticles (IONs) stand out from the crowd and constitute robust nanoplatforms since they can achieve high drug loading as well as targeting abilities stemming from their remarkable properties (magnetic and biological properties). These applications require precise design of the nanoparticles regarding several parameters which must be considered together in order to attain highest therapeutic efficacy.

Areas covered: This short review presents recent developments in the field of cancer targeted drug delivery using magnetic nanocarriers as drug delivery systems.

Expert opinion: The design of nanocarriers enabling efficient delivery of therapeutic compounds toward targeted locations is one of the major area of research in the targeted drug delivery field. By precisely shaping the structural properties of the iron oxide nanoparticles, drugs loaded onto the nanoparticles can be efficiently guided and selectively delivered toward targeted locations. With these goals in mind, special attention should be given to the pharmacokinetics and in vivo behavior of the developed nanocarriers.     

Current trends in chemical modifications of magnetic nanoparticles for targeted drug delivery in cancer chemotherapy

Abstract

Nowadays, magnetic nanoparticles (MNPs) have been rapidly investigated and attracted worldwide attention due to their great potential as mediators of heat for treating hyperthermia and their possibility to deliver drugs at specific locations, which can thereby limit systematic effects. Cancer therapy via MNPs proposes novel properties rather than normal methods such as almost zero side effects and a high-efficiency rate of effectiveness. The key aim of targeted drug delivery is to reduce side effects of the main cancer treatment that other usual chemotherapies will attend to the body, and thus controlling the effectiveness of the drug on a specific location that tumoral tissue exist. Herein, the high potential of MNPs has been studied, and different examples of their effectiveness on drug delivery and hypothermia therapy have been provided.     

Facile synthesis of PEI-based crystalline templated mesoporous silica with molecular chirality for improved oral delivery of the poorly water-soluble drug

The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120–130 nm with well-developed pore structure (S_BET: 1009.94 m²/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.     

Actively targeted nanocarriers for drug delivery to cancer cells

Introduction: Progressive breakthroughs in nanomedicine have been instrumental for the clinical translation of actively targeted drug-delivery approaches. Besides storing large payloads of drugs within the nanoparticle core, the conjugation of targeting moieties confers specific targeting ability to the nanoplatforms. In this respect, clinical results suggest that actively targeted nanocarriers can exhibit an overall improved antitumor efficacy, minimizing off-target toxicity.

Areas covered: This review article summarizes the advances in active targeting of nanocarriers to cancer cells. Specifically, we discuss the various types of nanocarriers, describe the receptors that are frequently overexpressed in solid tumors, and discuss how this approach can be used to improve clinical outcomes. We particularly focus on ongoing clinical trials of actively targeted nanoparticles that are yet to be clinically approved.

Expert opinion: Further investment in active targeting will likely pose clinical benefits. We envisage a future requiring the use of longitudinal measures in the clinical setting to profile the patients that are likely to benefit from actively targeted nanocarriers. At the preclinical stage, a complete picture of intratumoral barriers combined with a quantitative approach of the intratumoral fate of nanomaterials will be instrumental in defining more effective strategies to improve their clinical translation.     

基于介孔碳纳米粒包载胰岛素实现口服递药的研究

目的 利用介孔碳纳米粒(MCN)包载胰岛素从而实现口服缓释递药.方法 (1)制备与表征:制备包载胰岛素的介孔碳纳米粒(MCN-I),通过扫描电镜和透射电镜进行表征,高效液相色谱测定包封率和载药量,激光粒度仪测定粒径、多分散系数及Zeta电位,考察MCN-I的体外释放性能.(2)体内分布实验:按照体重将SD大鼠随机分为4...     

Antibacterial and anti-inflammatory drug delivery properties on cotton fabric using betamethasone-loaded mesoporous silica particles stabilized with chitosan and silicone softener

In this study, mesoporous silica particles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane, and used as a carrier for anti-inflammatory drug, betamethasone sodium phosphate. Drug-loaded silica particles were grafted on the cotton fabric surface using chitosan and polysiloxane reactive softener as a soft and safe fixing agent to develop an antibacterial cotton fabric with drug delivery properties. Cytometry assays revealed that synthesized silica have no cytotoxicity against human peripheral blood mononuclear cells. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as wound dressing. Drug delivery profile of the treated fabrics were investigated and compared. The drug release rate followed the conventional Higuchi model. The treated cotton fabrics were tested and evaluated using scanning electron microscope images, bending length, air permeability, washing durability and anti-bacterial properties. It was found that the chitosan-/softener-treated fabrics compounded with drug-loaded silica particles have a good drug delivery performance and exhibited a powerful antibacterial activity against both Escherichia coli and Staphylococcus aureus even after five washing cycles. The produced antibacterial cotton fabric with drug delivery properties could be proposed as a suitable material for many medical and hygienic applications.     

靶向给药研究的新进展

靶向给药可使治疗部位的药物浓度明显提高, 可减少用药量并使治疗费用降低, 降低药物对全身的毒副作用。因此, 靶向给药是目前研究的热点, 本文综述了近年来靶向给药的相关研究, 主要从被动靶向、主动靶向以及物理化学靶向3个方面阐述了靶向给药的研究进展。     

Stimuli-responsive nanoscale drug delivery systems for cancer therapy

Abstract

Currently, with the rapid development of nanotechnology, novel drug delivery systems (DDSs) have made rapid progress, in which nanocarriers play an important role in the tumour treatment. In view of the conventional chemotherapeutic drugs with many restrictions such as nonspecific systemic toxicity, short half-life and low concentration in the tumour sites, stimuli-responsive DDSs can deliver anti-tumour drugs targeting to the specific sites of tumours. Owing to precise stimuli response, stimuli-responsive DDSs can control drug release, so as to improve the curative effects, reduce the damage of normal tissues and organs, and decrease the side effects of traditional anticancer drugs. At present, according to the physicochemical properties and structures of nanomaterials, they can be divided into three categories: (1) endogenous stimuli-responsive materials, including pH, enzyme and redox responsive materials; (2) exogenous stimuli-responsive materials, such as temperature, light, ultrasound and magnetic field responsive materials; (3) multi-stimuli responsive materials. This review mainly focuses on the researches and developments of these novel stimuli-responsive DDSs based on above-mentioned nanomaterials and their clinical applications.     

Rod-shaped mesoporous silica nanoparticles for nanomedicine: recent progress and perspectives

Introduction: Interest in mesoporous silica nanoparticles for drug delivery has resulted in a good understanding of the impact of size and surface chemistry of these nanoparticles on their performance as drug carriers. Shape has emerged as an additional factor that can have a significant effect on delivery efficacy. Rod-shaped mesoporous silica nanoparticles show improvements in drug delivery relative to spherical mesoporous silica nanoparticles.

Areas covered: This review summarises the synthesis methods for producing rod-shaped mesoporous silica nanoparticles for use in nanomedicine. The second part covers recent progress of mesoporous silica nanorods by comparing the impact of sphere and rod-shape on drug delivery efficiency.

Expert opinion: As hollow mesoporous silica nanorods are capable of higher drug loads than most other drug delivery vehicles, such particles will reduce the amount of mesoporous silica in the body for efficient therapy. However, the importance of nanoparticle shape on drug delivery efficiency is not well understood for mesoporous silica. Studies that visualize and quantify the uptake pathway of mesoporous silica nanorods in specific cell types and compare the cellular uptake to the well-studied nanospheres should be the focus of research to better understand the role of shape in uptake.