Effect of mesoporous silica nanoparticles on cell viability and markers of oxidative stress

Abstract

In the recent years, the use of mesoporous silica nanoparticles (MSNs) has been extended in biomedical fields such as cancer therapy, drug and gene delivery, biosensors, and enzyme immobilization. Although nanomaterials are currently being widely used in modern technology, there is a lack of information regarding to the health and environmental implications of manufactured nanomaterials. In the present study, the effects of MSNs and surface functionalized MSNs on cell viability, markers of oxidative damages (mainly intracellular reactive oxygen species (ROS) formation), and oxidative DNA damage were investigated in vitro in rat pheochromocytoma PC12 cells. Following exposure of these nanoparticles (1.95–1000?µg/mL) to PC12 cells for 12 and 24?h, no significant reduction of cell viability was observed compared with control. Moreover, ROS formation and oxidative DNA damage were not significantly changed by these nanoparticles even at high concentrations or prolong exposures. In conclusion, the results showed that neither MSNs nor functionalized MSNs exhibited any remarkable in vitro toxic properties in PC12 cells even at high concentration.     

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.     

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.     

Gold nanoparticles: an era in bionanotechnology

Introduction: Gold nanoparticles have been efficiently and effectively used for the delivery of biomolecules and genes along with the potential to offer extremely sensitive diagnostics and imaging methods.

Areas covered: This review discusses the historical aspects, synthesis of gold nanoparticles, gold nanoparticles as drug delivery vehicles, photothermal effect of gold nanoparticles and the applications of gold nanoparticles. Gold nanoparticles with their unique optical properties may be useful as biosensors in living cells and has application in the field of drug delivery and photothermal therapy. Depending on the size, shape and degree of aggregation and nature of the protecting organic shells on their surface, gold nanoparticles can appear red, blue and other colors and emit bright resonance light of various wavelengths, which falls under visible region. Because of this property, gold nanoparticles have been extensively used as probes for sensing/imaging a wide range of analysts/targets such as proteins, cells and nucleic acids.

Expert opinion: Gold nanoparticles provide an admirable platform for the delivery of biomolecules and genes.     

Mesoporous silica nanoparticles: synthesis,classification, drug loading,pharmacokinetics, biocompatibility,and application in drug delivery

Introduction: Mesoporous silica nanoparticles (MSNs) feature a high surface area and large pore volume, uniform and tunable pore size, and stable framework; thus, they have been used extensively as drug carriers.

Areas covered: The synthesis, classification, and the latest generation of MSNs, drug loading methods, modification of MSNs, pharmacokinetic studies, biocompatibility, and toxicity of MSNs, and their application in drug delivery systems (DDS) are covered in this review.

Expert opinion: It is crucial to uncover the mechanism for the formation of MSNs. Before drug loading, the characteristics of MSNs should be taken into consideration. In addition, the porosity, particle size and morphology, surface oxidation and surface functionalization can also influence the in vivo fate of MSNs, which is worthy of further study. Coating MSNs with novel materials may improve their biocompatibility, control the release of drugs loaded into the MSNs or enhance the uptake of the coated MSNs by tumor cells. MSNs can also be used as carriers for combination therapy in the treatment of cancer. Despite the rapid development of MSNs, the biological effects of these biomaterials remain relatively less understood.     

Metallic nanoparticles: technology overview & drug delivery applications in oncology

Importance of the field: The targeted delivery of therapeutic agents to tumour cells is a challenge because most of the chemotherapeutic agents distribute to the whole body, which results in general toxicity and poor acceptance by patients and sometimes discontinuation of the treatment. Metallic nanoparticles have been used for a huge number of applications in various areas of medical treatment. Metallic nanoparticles are emerging as new carrier and contrast agents in cancer treatment. These metallic nanoparticles have been used for imaging of tumour cells by means of active and passive targeting. Recent advances have opened the way to site-specific targeting and drug delivery by these nanoparticles.

Areas covered in this review: This review summarizes the mechanisms of passive and active targeted drug delivery by metallic nanoparticles and their potential use in cancer theranostics.

What the reader will gain: The reader will gain information on the development of tumour cells, advantages of modern methods of cancer treatment over the traditional method, targeted delivery of anticancer agents using nanoparticles, influence of nanotechnology on the quality and expectancy of life, and challenges, implications and future prospects of metallic nanoparticles as probes in cancer treatment.

Take home message: The development of metallic nanoparticles is rapid and multidirectional, and the improved practical potential of metallic nanoparticle highlights their potency as new tools for future cancer therapeutics modalities.     

Gold nanoparticles: opportunities and challenges in nanomedicine

Importance of the field: Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of the drug and reduce potential side effects. Owing to this, substantial work has been done developing non-invasive and targeted tumor treatment with nanoscale metallic particles.

Areas covered in this review: This review focuses on the work done in the last few years developing gold nanoparticles as cancer therapeutics and diagnostic agents. However, there are challenges in using gold nanoparticles as drug delivery systems, such as biodistribution, pharmacokinetics and possible toxicity. Approaches to limit these issues are proposed.

What the reader will gain: Different approaches from several different disciplines are discussed. Potential clinical applications of these engineered nanoparticles are also presented.

Take home message: As a result of their unique size-dependent physicochemical and optical properties, adaptability, subcellular size and biocompatibility, these nanosized carriers offer a suitable means of transporting small molecules as well as biomacromolecules to diseased cells/tissues.     

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.     

Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents

ABSTRACT

Introduction: Bile acids are biological surfactants and signaling molecules with important paracrine and endocrine functions. The enterohepatic organotropism of bile acids turns these facial amphiphiles into attractive drug delivery systems for selective drug targeting to the liver or to enhance drug bioavailability by improving intestinal absorption and metabolic stability.

Areas covered: Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Therapeutic applications of bile acid derivatives as cytotoxic and neuroprotective agents are also addressed.

Expert opinion: Bile acids play an important role in modulating cancer therapy and novel derivatives with cytotoxic activity not restricted to the gastrointestinal tract can be expected. Selective toxicity targeting the bacterial membrane remains an attractive area of research for further development of bile acid-based bactericidal agents. On the other hand, the neuroprotective properties of some bile acids offer therapeutic potential in neurodegenerative disorders. Bile acid-based nanoparticles are also a growing research area due to the unique characteristics and tunable properties of these nanosystems. Therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.     

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。     

Silica nanoparticles on the oral delivery of insulin

Introduction: When intravenous or subcutaneous administration of insulin, various side effects or possible risks have been reported. Oral administration of insulin has significant advantages of convenience, painless and mimetic endogenous insulin pathway, and thus it presents patients compliance, protects pancreatic β cells and lessens adverse effects caused by long-term injection. This challenging oral delivery of insulin can be achieved by promising silica nanoparticles (SNs), especially mesoporous silica nanoparticles (MSNs), with controllable morphology and high loading efficiency. This review presents the synthesis and physiological behaviors of SNs such as in vivo and in vitro degradation, absorption, distribution, and excretion, as well as preparations of oral insulin based on SNs. As well, this review will provide insights for innovative oral delivery of SNs and insulin.

Areas covered: Promising SNs and MSNs have gained interests for application in oral drug delivery of insulin.

Expert opinion: After synthesis under proper conditions and methods, promising SNs with controllable structure and suitable stability can be synthesized. By improving permeability and penetration, achieving controlled release and adjusting physiological processes, functionalization on SNs by active groups, molecules, or polymers is necessary for oral delivery of insulin.     

Janus nanoparticles: materials,preparation and recent advances in drug delivery

Introduction: The term Janus particles was used to describe particles that are the combination of two distinct sides with differences in chemical nature and/or polarity on each face. Due to the exponential growth of interest on multifunctional nanotechnologies, such anisotropic nanoparticles are promising tools in the field of drug delivery.

Areas covered: The main preparation processes and the materials used have been described first. Then a specific focus has been done on therapeutic and/or diagnostic applications of Janus particles.

Expert opinion: Janus particles are demonstrated as interesting objects with advanced properties that combine features and functionalities of different materials in one single unit. Due to their dual structure, Janus particles are promising candidates for a variety of high-quality applications dealing with drug delivery purposes. Still, the main challenges for the future lie in the development of the preparation of shape-controlled and nano-sized particles with large-scale production processes and approved pharmaceutical excipients.     

基于钙离子驱动的药物负载构建光响应性介孔硅纳米粒的研究

目的 提高介孔硅纳米粒(mesoporous silicon nanoparticles，MSNs)中药物负载量，并使其具备光响应性等功能。方法 本研究采用模板法制备氨基化的介孔硅纳米粒(MSN-NH₂)，并通过钙离子负载的MSNs(MSN-Ca)诱导化疗药物阿霉素(Doxorubicin，Dox)及光热治疗药物Cypate、二氢卟吩e6(Ce6)的高效负载，制得光响应性载单药或多药的MSNs，并对其理化性质及释药特性进行研究。结果 钙离子可有效负载于MSNs内，并可以诱导Dox、Cypate、Ce6在MSNs孔道内的高效负载，其载药量可分别达到(28.5±1.4)%，(36.8±1.5)%，(36.6±1.7)%；MSN-Ca还可以实现Dox、Cypate、Ce6中的2种或3种药物共同负载。负载Cypate的MSNs具有良好的光热升温效果。载Dox的MSNs具有酸性pH响应性释放Dox的特点。785 nm激光照射可明显增强MSN-Ca-Dox/Cypate的Dox释放，具有光响应性释药的特点。结论 钙离子驱动的药物负载策略在多功能MSNs的构建及其抗肿瘤协同治疗研究中具有重要作用。     

‘Smart’ nanoparticles as drug delivery systems for applications in tumor therapy

Introduction: In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using ‘smart’ nanoparticles (NPs) as drug delivery systems, because they enable dramatic conformational changes in response to specific physical/chemical stimuli from the diseased cells for targeted and controlled drug release.

Areas covered: In this review, we first briefly summarize the characteristics of ‘smart’ NPs as drug delivery systems in medical therapy, and then discuss their targeting transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the applications of ‘smart’ NPs as drug delivery systems for tumor therapy.

Expert opinion: Biodegradable ‘smart’ NPs have the potential to achieve maximum efficacy and drug availability at the desired sites, and reduce the harmful side effects for healthy tissues in tumor therapy. It is necessary to select appropriate NPs and modify their characteristics according to treatment strategies of tumor therapy.     

The importance of nanoparticle shape in cancer drug delivery

Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.

Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery.

Expert opinion: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.     

Controlled synthesis and size effects of multifunctional mesoporous silica nanosystem for precise cancer therapy

Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20?nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80?nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80?nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy.     

Iron oxide magnetic nanoparticles as antimicrobials for therapeutics

Abstract

The use of iron oxide magnetic nanoparticles (IMNP) in medical and pharmaceutical areas dates to the beginning of the 1970s, as carriers. Some other uses to these nanoparticles are in vitro separation, magnetic resonance imaging and drug targeting agent. Many preparations containing IMNP have been described and used in drug delivery, hyperthermia, in vitro separation, tissue repair, cellular therapy, for magnetic separation, magnetic resonance imaging, as spoilers for magnetic resonance spectroscopy, and more recently as sensors for metabolites and other biomolecules. The use of these nanostructures as antibacterial agents has also been reported, which could kill some bacteria species causing no damage to the human host cells. Recently, they have been used as hyperthermia agents to treat infections or cancer, which are more susceptible than the healthy host’s cells. Engineering designs, physiochemical characteristics, biomedical applications of IMNP, toxicity and magnetic nanotoxicology have been discussed. However, the application of IMNP as antimicrobials is very important. Thus, this review explores the therapeutic activities of IMNP and their use as antimicrobial agents. These nanoparticles can be efficient for the treatment of microbial infections, probably acting as membrane permeability enhancer, damaging the cell wall or by generating reactive oxygen species.     

Nanodiamond-mediated drug delivery and imaging: challenges and opportunities

Introduction: The field of nanoparticle-based therapeutic systems is rapidly expanding encompassing a wide variety of practices ranging from detection to diagnosis to treatment. Recently a great potential of nanodiamond (ND) particles as a multimodal imaging/therapy platform has been demonstrated.

Areas covered: This review describes a unique set of properties of ND particles attractive for drug delivery and imaging applications and highlights the most recent ND-based multimodal imaging/therapy approaches and related biocompatibility studies. The spectrum of major advancements includes marked improvements in tumor treatment efficacy and safety based on integration of ND with doxorubicin (DOX). Recent progress of ND-mediated drug delivery in orthopedic, dental and ophthalmic applications is also discussed.

Expert opinion: ND particles possess a unique set of properties attractive for drug delivery applications, including exceptional biocompatibility, large carrier capacity and versatile surface chemistry properties, which enhance drug binding and provide sustainable drug release. Other unique attributes of NDs embrace bright stable fluorescence based on crystallographic defects. A roadmap toward a clinical translation comprises identification of ND-therapeutic compounds that display marked improvements over clinical standards with respects to efficacy, safety and cost.     

Cationic nanoparticles for cancer therapy

Importance of the field: The lack of selective delivery of therapeutic molecules to cancer cells remains a problem in cancer therapy. As a result of this non-selectivity, cytotoxic agents are delivered to both healthy and cancerous cells, resulting in severe side effects for the patient, eventually causing termination of therapy or ineffective therapy resulting in progression or recurrence of the disease. In this context, cationic polymers with net positive surface charge emerge as a promising option owing to their very strong cellular interaction properties and good cellular uptake.

Areas covered in this review: In this review, the structure, characteristics and preparation techniques for cationic nanoparticulate drug delivery systems are discussed in the light of cytotoxicity associated with cationic polymers and strong complement activation properties of cationic carrier systems on injection. In vivo behavior and biodistribution of cationic nanoparticles are also reviewed for a better understanding of biological interaction of cationic nanoparticles.

What the reader will gain: This review will give an insight to the properties of cationic polymers, including their advantages and drawbacks and drug/gene delivery systems based on cationic polymers intended for cancer therapy.

Take home message: Cationic polymer-based nanoparticles emerge as a promising group of nanosize carrier systems to the tumor cell level with a wide range of modification and application possibilities.     

Ultrasound-enhanced drug delivery for cancer

Introduction: Ultrasound, which has traditionally been used as a diagnostic tool, is increasingly being used in non-invasive therapy and drug delivery.

Areas covered: Of particular interest to this review is the rapidly accumulating evidence that ultrasound may have a key role to play both in improving the targeting and the efficacy of drug delivery for cancer. Currently available ultrasound-triggerable vehicles are first described, with particular reference to the ultrasonic mechanism that can activate release and the suitability of the size range of the vehicle used for drug delivery. Further mechanical and thermal effects of ultrasound that can enhance extravasation and drug distribution following release are then critically reviewed.

Expert opinion: Acoustic cavitation is found to play a potentially key role both in achieving targeted drug release and enhanced extravasation at modest pressure amplitudes and acoustic energies, whilst simultaneously enabling real-time monitoring of the drug delivery process. The next challenge in ultrasound-enhanced drug delivery will thus be to develop a new generation of drug-carrying nanoparticles which are of the right size range for delivery to tumours, yet still capable of achieving initiation of cavitation activity and drug release at modest acoustic pressures and energies that have no safety implications for the patient.