Nanoparticle-based Delivery Systems Research Articles

Overcoming the rising incidence and evolving mechanisms of antibiotic resistance by novel drug delivery approaches - An overview.

Antimicrobial resistance is a normal evolutionary process for microorganisms. Antibiotics exerted accelerated selective pressure that hasten bacterial resistance through mutation, and acquisition external genes. These genes often carry multiple antibiotic resistant determinants allowing the recipient microbe an instant "super-bug" status. The extent of Antimicrobial Resistance (AMR) has reached a level of global crisis, existing antimicrobials are no long effective in treating infections caused by AMR pathogens. The great majority of clinically available antimicrobial agents are administered through oral and intra-venous routes. Overcoming antibacterial resistance by novel drug delivery approach offered new hopes, particularly in the treatment of AMR pathogens in sites less assessible through systemic circulation such as the lung and skin. In the current review, we will revisit the mechanism and incidence of important AMR pathogens. Finally, we will discuss novel drug delivery approaches including novel local antibiotic delivery systems, hybrid antibiotics, and nanoparticle-based antibiotic delivery systems.

Novel lncRNA AL033381.2 Promotes Hepatocellular Carcinoma Progression by Upregulating PRKRA Expression.

Hepatocellular carcinoma (HCC) is a common malignant tumor that is characterized by aggressiveness and poor prognosis. Accumulating evidence indicates that oxidative stress plays a crucial role in carcinogenesis, whereas the potential mechanism between oxidative stress and carcinogenic effects remains elusive. In recent years, long noncoding RNAs (lncRNAs) in cancers have attracted extensive attention and have been shown to be involved in oxidative stress response and carcinogenesis. Nevertheless, the roles of lncRNA AL033381.2 in regulating the development and progression of HCC still remain unclear. The purpose of our study was to evaluate the potential effects and molecular mechanisms of AL033381.2 that may be involved in oxidative stress response in HCC. Using bioinformatics analyses based on the TCGA database, we screened and identified a novel lncRNA AL033381.2 in HCC, which may be involved in oxidative stress responses. qRT-PCR analysis revealed that AL033381.2 is upregulated in HCC tissues. Through in vitro and in vivo experiments, we found that AL033381.2 dramatically facilitates the growth and metastasis of HCC. Mechanistically, RNA pull-down experiments, mass spectrometry, PathArray™, and RIP were used to determine that AL033381.2 binds to PRKRA and may be involved in AL033381.2-mediated oncogenic functions in HCC cells. Moreover, rescue experiments demonstrated that PRKRA overexpression rescues the abilities of HCC cell proliferation, migration, and invasion that were affected by AL033381.2 knockdown. Furthermore, we produced a nanoparticle-based siRNA delivery system and tested its therapeutic effects in vivo. The results showed that the in vivo growth rate of the tumors treated with the nanoparticle/AL033381.2 siRNA complexes was dramatically lower than those treated with the nanoparticle/scramble siRNA complexes. Taken together, our results suggest that the novel lncRNA AL033381.2 may be involved in oxidative stress response by targeting oxidative stress-related genes in HCC. AL033381.2 plays vital oncogenic roles in HCC progression and may be a novel therapeutic marker for HCC diagnosis and treatment.

Kidney functional stages influence the role of PEG end-group on the renal accumulation and distribution of PEGylated nanoparticles.

Modification with polyethylene glycol (PEG), or PEGylation, has become a popular method to improve the efficiency of drug delivery in vivo using nanoparticle-based delivery systems. The PEG end-group plays an important role in the in vivo fate of PEGylated nanoparticles through its interactions with proteins in the serum and the cell membrane. However, the effects of PEG end-groups on the renal clearance of PEGylated nanoparticles remain unclear. Kidney function may also affect the renal accumulation and distribution of nanoparticles. Herein, we demonstrate that the accumulation and distribution of PEGylated nanoparticles in kidneys are significantly affected by both the PEG end-group and kidney function damage. Interestingly, compared to PEG with an amino or methoxy end-group, PEG with maleimide as the end-group markedly enhanced the accumulation of PEGylated nanoparticles in normal kidneys, which may improve renal clearance. However, obvious enhancements in the renal accumulation and medullary distribution of PEGylated nanoparticles are detected in kidneys with functional impairment. Damage to renal function further affects how the PEG end-group influences the accumulation and distribution of PEGylated nanoparticles in kidneys in vivo. Collectively, the findings provide deep insights into the interactions between PEGylated nanoparticles and kidneys in vivo.

Multimodal Targeted Nanoparticle-Based Delivery System for Pancreatic Tumor Imaging in Cellular and Animal Models

Multimodal Targeted Nanoparticle-Based Delivery System for Pancreatic Tumor Imaging in Cellular and Animal Models

Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier.

Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.

ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia.

With critical limb ischemia (CLI) being a multi-factorial disease, it is becoming evident that gene therapy with a multiple bio-functional growth factor could achieve better therapeutic outcomes. Cytochrome P450 epoxygenase-2J2 (CYP2J2) and its catalytic products epoxyeicosatrienoic acids (EETs) exhibit pleiotropic biological activities, including pro-angiogenic, anti-inflammatory and cardiovascular protective effects, which are considerably beneficial for reversing ischemia and restoring local blood flow in CLI. Here, we designed a nanoparticle-based pcDNA3.1-CYP2J2 plasmid DNA (pDNA) delivery system (nanoparticle/pDNA complex) composed of a novel three-arm star block copolymer (3S-PLGA-po-PEG), which was achieved by conjugating three-armed PLGA to PEG via the peroxalate ester bond. Considering the multiple bio-functions of CYP2J2-EETs and the sensitivity of the peroxalate ester bond to H2O2, this nanoparticle-based gene delivery system is expected to exhibit excellent pro-angiogenic effects while improving the high oxidative stress and inflammatory micro-environment in ischemic hindlimb. Our study reports the first application of CYP2J2 in the field of therapeutic angiogenesis for CLI treatment and our findings demonstrated good biocompatibility, stability and sustained release properties of the CYP2J2 nano-delivery system. In addition, this nanoparticle-based gene delivery system showed high transfection efficiency and efficient VEGF expression in vitro and in vivo. Intramuscular injection of nanoparticle/pDNA complexes into mice with hindlimb ischemia resulted in significant rapid blood flow recovery and improved muscle repair compared to mice treated with naked pDNA. In summary, 3S-PLGA-po-PEG/CYP2J2-pDNA complexes have tremendous potential and provide a practical strategy for the treatment of limb ischemia. Moreover, 3S-PLGA-po-PEG nanoparticles might be useful as a potential non-viral carrier for other gene delivery applications.

Nano-Particulate Platforms for Vaccine Delivery to Enhance Antigen-Specific CD8+ T-Cell Response.

Vaccines remain the most effective way to protect populations against deathly infectious diseases. Several disadvantages associated with the traditional vaccines that use whole pathogens have led to the development of alternative strategies including the useofrecombinant subunit vaccines. Subunit vaccines are, in general, safer than whole pathogens but tend to be less immunogenic due to thelackofmolecular cuesthat are typically found on whole pathogens.To enhance immunogenicity, the subunit antigen can be administeredwith adjuvants that stimulate the innate immune system as a means to steer the quality andmagnitude of the adaptive immune response. Novel classes of adjuvants are formulatedusing particle-based platformssuch as virus-like particles, liposomes, and polymeric nanoparticles. These particle-based systemspresent antigens in ways reminiscent of wholepathogens. Such platforms offer several advantages that include co-delivery of antigen along with innate immune stimulators in ahighly immunogenic format. Here we describe our recent efforts to synthesize, characterize, and validate two promising nanoparticle-based delivery systems anddemonstrate their potential to induce antigen-specific CD8+ T cell responses, essential in clearing infectionwith intracellular pathogens, such as viruses and bacteria, and eradicating tumors.

Nanocarriers for Inner Ear Disease Therapy.

Hearing loss is a common disease due to sensory loss caused by the diseases in the inner ear. The development of delivery systems for inner ear disease therapy is important to achieve high efficiency and reduce side effects. Currently, traditional drug delivery systems exhibit the potential to be used for inner ear disease therapy, but there are still some drawbacks. As nanotechnology is developing these years, one of the solutions is to develop nanoparticle-based delivery systems for inner ear disease therapy. Various nanoparticles, such as soft material and inorganic-based nanoparticles, have been designed, tested, and showed controlled delivery of drugs, improved targeting property to specific cells, and reduced systemic side effects. In this review, we summarized recent progress in nanocarriers for inner ear disease therapy. This review provides useful information on developing promising nanocarriers for the efficient treatment of inner ear diseases and for further clinical applications for inner ear disease therapy.

VirPorters: Insights into the action of cationic and histidine-rich cell-penetrating peptides

The utilization of nanoparticles for the intracellular delivery of theranostic agents faces one substantial limitation. Sequestration in intracellular vesicles prevents them from reaching the desired location in the cytoplasm or nucleus to deliver their cargo. We investigated whether three different cell-penetrating peptides (CPPs), namely, octa-arginine R8, polyhistidine KH27K and histidine-rich LAH4, could promote cytosolic and/or nuclear transfer of unique model nanoparticles—pseudovirions derived from murine polyomavirus. Two types of CPP-modified pseudovirions that carry the luciferase reporter gene were created: VirPorters-IN with CPPs genetically attached to the capsid interior and VirPorters-EX with CPPs noncovalently associated with the capsid exterior. We tested their transduction ability by luciferase assay and monitored their presence in subcellular fractions. Our results confirmed the overall effect of CPPs on the intracellular destination of the particles and suggested that KH27K has the potential to improve the cytosolic release of pseudovirions. None of the VirPorters caused endomembrane damage detectable by the Galectin-3 assay. Remarkably, a noncovalent modification was required to promote high transduction of the reporter gene and cytosolic delivery of pseudovirions mediated by LAH4. Together, CPPs in different arrangements have demonstrated their potential to improve pseudovirion invasion into cells, and these findings could be useful for the development of other nanoparticle-based delivery systems.

Modulation of intrinsic inhibitory checkpoints using nano-carriers to unleash NK cell activity.

Natural killer (NK) cells provide a powerful weapon mediating immune defense against viral infections, tumor growth, and metastatic spread. NK cells demonstrate great potential for cancer immunotherapy; they can rapidly and directly kill cancer cells in the absence of MHC‐dependent antigen presentation and can initiate a robust immune response in the tumor microenvironment (TME). Nevertheless, current NK cell‐based immunotherapies have several drawbacks, such as the requirement for ex vivo expansion of modified NK cells, and low transduction efficiency. Furthermore, to date, no clinical trial has demonstrated a significant benefit for NK‐based therapies in patients with advanced solid tumors, mainly due to the suppressive TME. To overcome current obstacles in NK cell‐based immunotherapies, we describe here a non‐viral lipid nanoparticle‐based delivery system that encapsulates small interfering RNAs (siRNAs) to gene silence the key intrinsic inhibitory NK cell molecules, SHP‐1, Cbl‐b, and c‐Cbl. The nanoparticles (NPs) target NK cells in vivo, silence inhibitory checkpoint signaling molecules, and unleash NK cell activity to eliminate tumors. Thus, the novel NP‐based system developed here may serve as a powerful tool for future NK cell‐based therapeutic approaches.

590: A lipid nanoparticle–based delivery system for the treatment of CF

590: A lipid nanoparticle–based delivery system for the treatment of CF

Preparation and characterization of BSA as a model protein loaded chitosan nanoparticles for the development of protein-/peptide-based drug delivery system

BackgroundThe purpose of this study was to develop protein-/peptide-loaded nanoparticle-based delivery system, which can efficiently deliver therapeutic molecules to the lung via pulmonary delivery. The chitosan nanoparticles were prepared by the ionic gelation method, and bovine serum albumin was used as a model protein. These nanoparticles were characterized for size, zeta potential, encapsulation efficiency, cell cytotoxicity, uptake study, release profile and size distribution and uniformity. The chemical interaction of chitosan and protein was studied by XRD and FTIR. The integrity assessment of encapsulated protein into nanoparticle was studied by native and SDS-PAGE gel electrophoresis.ResultsThe size and zeta potential of BSA nanoparticles were 193.53 ± 44.97 to 336.36 ± 94.63 and 12.73 ± 0.41 to 18.33 ± 0.96, respectively, with PDI values of 0.35–0.45. The encapsulation efficiency was in the range of 80.73 ± 6.37% to 92.34 ± 1.72%. The cumulative release of the BSA from the nanoparticles was 72.56 ± 6.67% in 2 weeks. The BSA-loaded nanoparticles showed good uptake and no significant cytotoxicity observed into the A549 cell line. In this study, it was also observed that during nanoparticles’ synthesis protein structure and integrity is not compromised. The nanoparticles showed controlled and sustained release with initial burst release. In TEM images, it was shown that nanoparticles’ distribution is uniform within nanometre range.ConclusionFrom this study, it was concluded that nanoparticles prepared by this method are suitable to deliver protein/peptide into the cells without any degradation of protein during process of nanoparticle fabrication.

Ethanol-soluble polysaccharide from sugar beet pulp for stabilizing zein nanoparticles and improving encapsulation of curcumin

Ethanol-soluble polysaccharide (ESP) is a highly ethanol-soluble (85% v/v) fraction from the precipitation process of sugar beet pectin and holds the potential to be utilized for food purposes. This study aimed to explore ESP as a coating polymer to stabilize zein nanoparticles against agglomeration via co-dissolving ESP and zein in an ethanol/water mixture (85% v/v) and subsequently dispersing into the water to form composite nanoparticles. Structural analyses showed that the ESP contained 28.3 wt% galacturonic acid, 45.7 wt% neutral sugar, and 17.6 wt% protein, and that its average molecular weight was 93,157 Da. In this study, we fabricated ESP-coated zein (zein-ESP) nanoparticles with a diameter of around 248 nm using the antisolvent co-precipitation method. These zein-ESP nanoparticles were stable over a wide pH range of 2.0–8.0 when the ESP:zein mass ratio was higher than 0.6:1. Additionally, the nanoparticles exhibited good stability in environmental stresses such as sodium ion concentrations of 400 mM and high temperatures of 90 °C (for 120 min). The encapsulation efficiency of Cur improved significantly, from 68.5% with the zein nanoparticles to 88.7% with the zein-ESP nanoparticles. When encapsulated by zein-ESP nanoparticles, Cur presented as an amorphous form and was released in a sustained and controlled manner after exposure to simulated gastrointestinal fluids, resulting in enhanced solubility and in vitro bioaccessibility, as compared with the free Cur. Altogether, ESP has great potential to stabilize zein nanoparticles-based delivery systems for hydrophobic bioactive compounds with enhanced water solubility and encapsulation efficiency for use in the food and pharmaceutical industries.

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform.

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Biocontrol Delivery System of <i>Trichoderma harzianum</i> Formulated in Graphite and Silica Nano Particles to Control <i>Rhizoctonia solani</i> on Tomato Plants

This paper reports the performance of a graphite and silica nanoparticles-based delivery system forT. harzianumin controlling the in vitro growth ofR. solaniand damping-off disease on tomato plants. The in vitro and in vivo experiments were arranged in the randomized complete block design. The in vitro treatment was a dual culture ofR. solaniandT. harzianumin the various components of formulation on PDA, i.e.,T. harzianum+ 5 wt.% graphite,T. harzianum+ 1wt.% silica NPs.,T. harzianum+ 5 wt.% graphite + 1 wt.% silica nanoparticles,T. harzianum, 5 wt.% graphite, 1 wt.% silica nanoparticles, fungicide (mancozeb), and a control. The in vivo treatment included the application ofT. harzianumin the same compositions as the in vitro treatment, except that there were two controls i.e., inoculated and noninoculated tomato plants withR. solani.T. harzianumby soaking tomato seeds in the formulation suspensions before planting. The results showed that all formulation compositions were able to inhibit the in vitro growth ofR. solani. The inhibitions of the colony growth ofR. solanicaused by formulated and non-formulatedT. harzianumwere the same. This proved that graphite and silica NPs did not resist to the ability ofT. harzianumin controllingR. solani, indicated that the formulation was promising to develop. However, the inhibition of damping-off disease incidence on tomato plants caused by formulatedT. harzianumwas the same as the non-formulated one only on day 7 after treatments. On days 14, 21, and 28, the inhibitions were lower than the non-formulated ones. It was suggested to reapply the formulation ofT. harzianumin the soil at planting and several days after.

Role of NKT Cells during Viral Infection and the Development of NKT Cell-Based Nanovaccines.

Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and the strategies of viruses to evade the functioning of NKT cell have been illustrated. The nanoparticle-based formulations have superior immunoadjuvant potential by facilitating the efficient antigen processing and presentation that favorably elicits the antigen-specific immune response. Finally, the immunoadjuvant potential of the NKT cell ligand was explored in the development of antiviral vaccines. The use of an NKT cell-activating nanoparticle-based vaccine delivery system was supported in order to avoid the NKT cell anergy. The results from the animal and preclinical studies demonstrated that nanoparticle-incorporated NKT cell ligands may have potential implications as an immunoadjuvant in the formulation of an effective antiviral vaccine that is capable of eliciting the antigen-specific activation of the cell-mediated and humoral immune responses.

Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer.

Simple SummaryConventional anti-cancer treatments for metastatic tumors include chemotherapy and radiation. These approaches can result in harmful side-effects and, in the vast majority of cases, are not curative. Recently, novel treatments have been developed in order to stimulate the host immune system to fight cancer. This type of therapeutic approach, called immunotherapy, has gained a lot of attention in recent years due to discoveries that have deciphered the immunosuppressive role of the tumor microenvironment and underpinning molecular signals. To enhance the delivery of therapeutic drugs to the tumor site, nanoparticle-based delivery systems can be used to reduce off-target effects, and to modulate immune cells present in the tumor microenvironment. This novel therapeutic approach can synergize with other immunotherapies such as immune checkpoint blockade inhibitors and adoptive cell therapy, by enhancing the infiltration of activated immune cells to the tumor site, and by limiting local immunosuppression.A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies.

A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis

Endophthalmitis is an infectious disease that affects the entire eye spreading to the internal retinal layers and the vitreous and causes severe sight-threatening conditions. Current treatment strategies rely on intraocular injections of antibiotics that are invasive, may lead to procedural complications and, ultimately, blindness. In this study, we developed a non-invasive strategy as an eyedrop containing nanoparticle-based dual-drug delivery system in which the hydrophobic poly-L-lactide core was loaded with azithromycin or triamcinolone acetonide, and the hydrophilic shell was made of chitosan. The developed nanoparticles were ~200–250 nm in size, spherical in shape, moderately hydrophilic, lysozyme tolerant, cytocompatible, and hemocompatible. Application of these chitosan-coated nanoparticles as eye drops to C57BL/6 mice showed higher bioavailability in choroid and retina when compared to the uncoated nanoparticles. The delivery system showed sustained release of drug for 300 h and exhibited antimicrobial effects against Gram-positive and Gram-negative bacteria and anti-inflammatory effects on activated microglial cells. Interestingly, the combination of the nanoparticles loaded with azithromycin and the nanoparticles loaded with triamcinolone acetonide acted synergistically as compared to either of the nanoparticles/drugs alone. Overall, the developed dual-drug delivery system is non-invasive, has antimicrobial and anti-inflammatory effects, and shows potential as an eye drop formulation against endophthalmitis.

In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint.

Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.4% ± 22.87, rTDSPC 18.13% ± 12.07, hBMSC 18.23% ± 14.80, hSDSC 26.63% ± 8.81) and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio (2:50, 4:50, or 6:50 w/w mRNA:NPs) had no impact. However, metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response. Finally, we demonstrate the feasibility of transfecting extracellular matrix-rich 3D cell culture constructs using the nanoparticle system, making it a promising transfection strategy for musculoskeletal tissues that exhibit a complex, dense extracellular matrix.

Metal-Organic Frameworks-Based Nanomaterials for Drug Delivery.

The composition and topology of metal-organic frameworks (MOFs) are exceptionally tailorable; moreover, they are extremely porous and represent an excellent Brunauer–Emmett–Teller (BET) surface area (≈3000–6000 m2·g−1). Nanoscale MOFs (NMOFs), as cargo nanocarriers, have increasingly attracted the attention of scientists and biotechnologists during the past decade, in parallel with the evolution in the use of porous nanomaterials in biomedicine. Compared to other nanoparticle-based delivery systems, such as porous nanosilica, nanomicelles, and dendrimer-encapsulated nanoparticles, NMOFs are more flexible, have a higher biodegradability potential, and can be more easily functionalized to meet the required level of host–guest interactions, while preserving a larger and fully adjustable pore window in most cases. Due to these unique properties, NMOFs have the potential to carry anticancer cargos. In contrast to almost all porous materials, MOFs can be synthesized in diverse morphologies, including spherical, ellipsoidal, cubic, hexagonal, and octahedral, which facilitates the acceptance of various drugs and genes.