Mesoporous Silica Nanoparticles for Drug Delivery

In recent years, nanomedicine has emerged at the forefront of nanotechnology, generating great expectations in the biomedical field. Researchers are developing novel nanoparticles for both diagnostic applications using imaging technology and treatment purposes through drug delivery technologies. Among all the available nanoparticles, inorganic mesoporous silica nanoparticles are the newcomers to the field, contributing with their unique and superlative properties. A brief overview of the most recent progress in the synthesis of mesoporous silica nanoparticles and their use as drug delivery nanocarriers is provided. The latest trends in this type of nanoparticles and their use in modern medicine are discussed, highlighting the significant impact that this technology might have in the near future.     

Doxorubicin‐Conjugated Immuno‐Nanoparticles for Intracellular Anticancer Drug Delivery

A polymeric nanoparticle comprised of surface furan groups is used to bind, by Diels–Alder (DA) coupling chemistry, both targeting anti‐human epidermal growth factor receptor 2 (anti‐HER2) antibodies and chemotherapeutic doxorubicin (DOX) for targeted, intracellular delivery of DOX. In this new approach for delivery, where both chemotherapeutic and targeting ligand are attached, for the first time, to the surface of the delivery vehicle, the nuclear localization of DOX in HER2‐overexpressing breast cancer SKBR‐3 cells is demonstrated, as determined by confocal laser scanning microscopy. Flow cytometric analysis shows that the conjugated DOX maintains its biological function and induces similar apoptotic progression in SKBR‐3 cells as free DOX. The viable cell counts of SKBR‐3 cancer cells following incubation with different nanoparticle formulations demonstrates that the combined DOX and anti‐HER2 nanoparticle is more efficacious than the nanoparticle formulation with either DOX or anti‐HER2 alone. While free DOX shows similar cytotoxicity against both cancerous SKBR‐3 cells and healthy HMEC‐1 cells, the combined DOX‐anti‐HER2 nanoparticle is significantly more cytotoxic against SKBR‐3 cells than HMEC‐1 cells, suggesting the benefit of nanoparticle‐conjugated DOX for cell type‐specific targeting. The DOX‐conjugated immuno‐nanoparticle represents an entirely new method for localized co‐delivery of chemotherapeutics and antibodies.     

Site‐Selectively Coated,Densely‐Packed Microprojection Array Patches for Targeted Delivery of Vaccines to Skin

Densely packed dry‐coated microprojections are shown to deliver vaccines to targeted locations within the skin that are rich in immune cells, thus inducing protective immune responses against a lethal virus challenge. Selectively limiting the antigen coating to the tips of the projections, which penetrate the skin, would significantly reduce the amount of vaccine required in immunization. In this paper a simple technique, dip‐coating the microprojections, is introduced to meet this goal. By increasing the coating solution viscosity, an otherwise strong capillary action is mitigated and the desired controlled coating length on projections is achieved. Following application to the skin, most of the coated vaccine material is rapidly released from the projections (82.6% in mass within 2 min) to the target locations within the skin strata and a potent immune response is induced when a conventional influenza vaccine (Fluvax) is tested in a mouse model. The utility of this coating approach to a variety of molecules representative of vaccines (e.g., chicken egg ovalbumin (OVA) protein, DNA, and fluorescent dyes) is demonstrated. These collective attributes, together with the simplicity of the approach, position the dip‐coating method for practical utility in large vaccination campaigns.     

Biodegradable Dextran Nanogels for RNA Interference: Focusing on Endosomal Escape and Intracellular siRNA Delivery

The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA‐loaded nanogels can be internalized by HuH‐7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza‐derived fusogenic peptide (diINF‐7) can significantly improve the silencing efficiency of siRNA‐loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA.     

Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

The efficient and specific delivery of nanoparticles (NPs) to brain tumors is crucial for successful glioma treatment. Heparin‐based polymers decorated with two peptides self‐assemble into multi‐functional NPs that specifically target glioma cells. These NPs re‐self‐assemble to a smaller size in blood, which is beneficial for in‐vivo brain drug delivery. The hydrodynamic size of one type of these NPs is 63 ± 11 nm under blood‐mimic conditions (10% fetal bovine serum), but it is 164 ± 16 nm in water. Additionally their zeta potential is more neutral in the blood‐mimic conditions. Transmission electron microscopy reveals the morphology of the spherical NPs. In vitro experiments demonstrate that the NPs exhibit a high cellular uptake and the ability to efficiently discourage proliferation, endothelial‐lined vessels, and vasculogenic mimicry. In vivo studies demonstrate that the NPs can by‐pass the normal blood–brain and blood–(brain tumor) barriers and specifically accumulate in glioma tissues; moreover, they present an excellent anti‐glioma effect in subcutaneous/intracranial glioma‐bearing mice. Their superiority is due to their appropriate size in blood and the synergic effect arising from their targeting of two different receptors. The data suggests that these NPs are ideal for anti‐glioma therapy.     

Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery

Microneedles are emerging as a minimally invasive drug delivery alternative to hypodermic needles. Current material systems utilized in microneedles impose constraints hindering the further development of this technology. In particular, it is difficult to preserve sensitive biochemical compounds (such as pharmaceuticals) during processing in a single microneedle system and subsequently achieve their controlled release. A possible solution involves fabricating microneedles systems from the biomaterial silk fibroin. Silk fibroin combines excellent mechanical properties, biocompatibility, biodegradability, benign processing conditions, and the ability to preserve and maintain the activity of biological compounds entrained in its material matrix. The degradation rate of silk fibroin and the diffusion rate of the entrained molecules can be controlled simply by adjusting post‐processing conditions. This combination of properties makes silk an ideal choice to improve on existing issues associated with other microneedle‐based drug delivery system. In this study, a fabrication method to produce silk biopolymer microstructures with the high aspect ratios and mechanical properties required to manufacture microneedle systems is reported. Room temperature and aqueous‐based micromolding allows for the bulk loading of these microneedles with labile drugs. The drug release rate is decreased 5.6‐fold by adjusting the post‐processing conditions of the microneedles, mainly by controlling the silk protein secondary structure. The release kinetics are quantified in an in vitro collagen hydrogel model, which allows tracking of the model drug. Antibiotic loaded silk microneedles are manufactured and used to demonstrate a 10‐fold reduction of bacterial density after their application. The processing strategies developed in this study can be expanded to other silk‐based structural formats for drug delivery and biologicals storage applications.     

Mussel‐Inspired Electrospun Smart Magnetic Nanofibers for Hyperthermic Chemotherapy

A method for the versatile synthesis of novel, mussel‐inspired, electrospun nanofibers with catechol moieties is reported. These mussel‐inspired nanofibers are used to bind iron oxide nanoparticles (IONPs) and the borate‐containing anticancer drug Bortezomib (BTZ) through a catechol metal binding mechanism adapted from nature. These smart nanofibers exhibit a unique conjugation of Bortezomib to their 1, 2‐benzenediol (catechol) moieties for enabling a pH‐dependent drug delivery towards the cancer cells and the IONPs via strong coordination bonds for exploiting the repeated application of hyperthermia. Thus the synergistic anticancer effect of these mussel‐inspired magnetic nanofibers were tested in vitro for the repeated application of hyperthermia along with the chemotherapy and found that the drug‐bound catecholic magnetic nanofibers exhibited excellent therapeutic efficacy for potential anticancer treatment.     

Latch Applicator for Efficient Delivery of Dissolving Microneedles Based on Rapid Release of Elastic Strain Energy by Thumb Force (Adv. Funct. Mater. 11/2023)

Dissolving microneedle (DMN) is an attractive alternative to parenteral and enteral drug administration owing to its painless self-administration and safety due to non-generation of medical waste. For reproducible and efficient DMN administration, various DMN application methods, such as weights, springs, and electromagnetic devices, have been studied. However, these applicators have complex structures that are complicated to use and high production costs. In this study, a latch applicator that consists of only simple plastic parts and operates via thumb force without any external complex device is developed. Protrusion-shaped latches and impact distances are designed to accumulate thumb force energy through elastic deformation and to control impact velocity. The optimized latch applicator with a pressing force of 25 N and an impact velocity of 5.9 m s⁻¹ fully inserts the drug-loaded tip of the two-layered DMN into the skin. In an ovalbumin immunization test, DMN with the latch applicator shows a significantly higher IgG antibody production rate than that of intramuscular injection. The latch applicator, which provides effective DMN insertion and a competitive price compared with conventional syringes, has great potential to improve delivery of drugs, including vaccines.     

Targeted Delivery of Anesthetic Agents to Bone Tissues using Conductive Microneedles Enhanced Iontophoresis for Painless Dental Anesthesia

Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual-role, creating micro-conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low-voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.     

Porous Silicon Nanodiscs for Targeted Drug Delivery

There is a strong demand for techniques that allow the fabrication of biocompatible porous nanoparticles for drug delivery applications. In this work, a new method to fabricate size‐ and shape‐controlled porous silicon (pSi) nanodiscs is described. The process relies on a combination of colloidal lithography and metal‐assisted chemical etching. Height and diameter of the pSi nanodiscs can be easily adjusted. The nanodiscs are degradable in physiological milieu and are nontoxic to mammalian cells. In order to highlight the potential of the pSi nanodiscs in drug delivery, an in vitro investigation that involved loading of nanodiscs with the anticancer agent camptothecin and functionalization of the nanodisc periphery with an antibody that targets receptors on the surface of neuroblastoma cells is carried out. The thus‐prepared nanocarriers are found to selectively attach to and kill cancer cells.     

Near‐Infrared Fluorescent Silica/Porphyrin Hybrid Nanorings for In Vivo Cancer Imaging

Ring‐shaped silica nanoparticles are synthesized with a high tetrakis(4‐carboxyphenyl)porphyrin (TCPP) content or silica/TCPP hybrid nanorings (HNRs) using a one‐pot sol‐gel reaction with a TCPP‐binding silica precursor for fluorescence imaging of tumor. The shape of the HNRs is a reflection of abundant ring‐shaped TCPP aggregates in the silica matrix. The HNRs are of a size that makes them susceptible to the enhanced permeability and retention effect. For comparison, the TCPP‐doped silica nanoparticles are synthesized using a conventional method. The nanoparticles are spherical in shape because little TCPP is contained in the silica matrix and are designated as TCPP‐containing silica nanospheres (NSs). The absorption bands of the HNRs shift by about 20 nm toward longer wavelengths compared with the TCPP bands. This redshift leads the excitation wavelength of the HNRs into the near‐infrared (NIR) region. Therefore, the HNRs are excited by NIR light to emit strong fluorescence, although the NSs emit no fluorescence. The PEGylated HNRs (PEG‐HNRs) are uncharged and possess a significantly longer blood circulation time than PEG‐NSs. The PEG‐HNRs accumulate in tumor through multiple factors including their size, uncharged surface, unique shape, and long circulation time in blood, resulting in the acquisition of clear images of tumor.     

Lipid Nanoparticles for Broad-Spectrum Nucleic Acid Delivery

Lipid nanoparticles (LNPs) are the most advanced nonviral modality for nucleic acid (NA) delivery, and have recently gained enormous attention in the fields of RNA therapeutics and vaccine development. Here, ionizable adamantane-based lipidoids named XMaNs, which circumvent the usual need for laborious optimization of LNP components for highly diverse types of NAs, are described. The non-toxic XMaN6 lipidoid is highly versatile in entrapment and delivery of siRNA, mRNA, plasmid DNA, and a cyclic dinucleotide. XMaN6-based LNPs efficiently deliver: 1) siRNA into human primary hepatocytes and cell lines that are hard-to-transfect; 2) mRNA into mouse liver; 3) plasmid DNA; 4) 2′,3′-cGAMP into cells and activated the cGAS-STING pathway three orders of magnitude more efficiently than 2′,3′-cGAMP alone. To our knowledge, such universality in delivering different NA types has not been previously described and can accelerate translation of LNPs into the clinic.     

新型MEMS微针设计及其力学性能

描述了三种新型MEMS微针的结构设计及制备方法.针对微针的实际使用要求,对微针的固体力学性质及微通道内液体的流动情况进行了理论分析和数值模拟.结果表明,所设计的三种微针的强度可以保证安全地进行皮肤注射,且适于进行药剂的微量传输.     

新型MEMS微针设计及其力学性能

描述了三种新型MEMS微针的结构设计及制备方法.针对微针的实际使用要求,对微针的固体力学性质及微通道内液体的流动情况进行了理论分析和数值模拟.结果表明,所设计的三种微针的强度可以保证安全地进行皮肤注射,且适于进行药剂的微量传输.     

Metal Species–Encapsulated Mesoporous Silica Nanoparticles: Current Advancements and Latest Breakthroughs

Despite their advantageous morphological attributes and attractive physicochemical properties, mesoporous silica nanoparticles (MSNs) are merely supported as carriers or vectors for a reason. Incorporating various metal species in the confined nanospaces of MSNs (M‐MSNs) significantly enriches their mesoporous architecture and diverse functionalities, bringing exciting potentials to this burgeoning field of research. These incorporated guest species offer enormous benefits to the MSN hosts concerning the reduction of their eventual size and the enhancement of their performance and stability, among other benefits. Substantially, the guest species act through contributing to reduced aggregation, augmented durability, ease of long‐term storage, and reduced toxicity, attributes that are of particular interest in diverse fields of biomedicine. In this review, the first aim is to discuss the current advancements and latest breakthroughs in the fabrication of M‐MSNs, emphasizing the pros and cons, the confinement of various metal species in the nanospaces of MSNs, and various factors influencing the encapsulation of metal species in MSNs. Further, an emphasis on potential applications of M‐MSNs in various fields, including in adsorption, catalysis, photoluminescence, and biomedicine, among others, along with a set of examples is provided. Finally, the advances in M‐MSNs with perspectives are summarized.     

Microstructured Biodegradable Fibers for Advanced Control Delivery

Biodegradable polymers are increasingly employed at the heart of therapeutic devices. Particularly in the form of thin and elongated fibers, they offer an effective strategy for controlled release in a variety of biomedical configurations such as sutures, scaffolds, wound dressings, surgical or imaging probes, and smart textiles. So far however, the fabrication of fiber‐based drug delivery systems has been unable to fulfill significant requirements of medicated fibers such as multifunctionality, adequate mechanical strength, drug loading capability, and complex release profiles of multiple substances. Here, a novel paradigm in the design and fabrication of microstructured biodegradable fibers with tailored mechanical properties and capable of predefined release patterns from multiple reservoirs is proposed. Different biodegradable polymers compatible with the scalable thermal drawing process are identified, and their release properties as thin films of various thicknesses in the fiber form are experimentally investigated and modeled. Multimaterial microstructured fibers with predictable complex release profiles of potentially different substances are then designed and fabricated. Moreover, the tunability of the mechanical properties via tailoring the drawing process parameters is demonstrated, as well as the ability to weave such fibers. This work establishes a novel platform for biodegradable microstructured fibers for applications in implants, sutures, wound dressing, or tissue scaffolds.     

Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino‐β‐cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β‐cyclodextrin/adamantane complexation. The non‐cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate‐receptor‐rich HeLa cancer cells through receptormmediated endocytosis, while folate‐receptor‐poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β‐cyclodextrin capping rings by cleaving the pre‐installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug‐delivery efficacy of the multifunctional nanoparticles is attributed to the co‐operative effects of folate‐mediated targeting and stimuli‐triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.     

Remote‐Loaded Platelet Vesicles for Disease‐Targeted Delivery of Therapeutics

The recent emergence of biomimetic nanotechnology has facilitated the development of next‐generation nanodelivery systems capable of enhanced biointerfacing. In particular, the direct use of natural cell membranes can enable multivalent targeting functionalities. Herein, this study reports on the remote loading of small molecule therapeutics into cholesterol‐enriched platelet membrane‐derived vesicles for disease‐targeted delivery. Using this approach, high loading yields for two model drugs, doxorubicin and vancomycin, are achieved. Leveraging the surface markers found on platelet membranes, the resultant nanoformulations demonstrate natural affinity toward both breast cancer cells and methicillin‐resistant Staphylococcus aureus. In vivo, this translates to improved disease targeting, increasing the potency of the encapsulated drug payloads compared with free drugs and the corresponding nontargeted nanoformulations. Overall, this work demonstrates that the remote loading of drugs into functional platelet membrane‐derived vesicles is a facile means of fabricating targeted nanoformulations, an approach that can be easily generalized to other cell types in the future.