Mesoporous silica nanoparticles (MSNs), one of the important porous materials, have garnered interest owing to their highly attractive physicochemical features and advantageous morphological attributes. They are of particular importance for use in diverse fields including, but not limited to, adsorption, catalysis, and medicine. Despite their intrinsic stable siliceous frameworks, excellent mechanical strength, and optimal morphological attributes, pristine MSNs suffer from poor drug loading efficiency, as well as compatibility and degradability issues for therapeutic, diagnostic, and tissue engineering purposes. Collectively, the desirable and beneficial properties of MSNs have been harnessed by modifying the surface of the siliceous frameworks through incorporating supramolecular assemblies and various metal species, and through incorporating supramolecular assemblies and various metal species and their conjugates. Substantial advancements of these innovative colloidal inorganic nanocontainers drive researchers in promoting them toward innovative applications like stimuli (light/ultrasound/magnetic)-responsive delivery-associated therapies with exceptional performance in vivo. Here, a brief overview of the fabrication of siliceous frameworks, along with discussions on the significant advances in engineering of MSNs, is provided. The scope of the advancement in terms of structural and physicochemical attributes and their effects on biomedical applications with a particular focus on recent studies is emphasized. Finally, interesting perspectives are recapitulated, along with the scope toward clinical translation.

https://espace.library.uq.edu.au/view/UQ:e768bd6/UQe768bd6_OA.pdf

Nanoarchitectured Structure and Surface Biofunctionality of Mesoporous Silica Nanoparticles

Objective:To investigate the effectiveness of curcumin,a natural polyphenoiic compound with antioxidant and anti-inflammatory activities,on the frequency of symptoms of anxiety and depression in obese individuals.Methods:In this double blind,cross-over trial,30 obese subjects were randomized to receive either curcumin(1 g/day) or placebo for a period of 30 days.Following a wash-out interval of 2 weeks,each subject was crossed over to the alternative regimen for a further 30 days.Severity of anxiety and depression was assessed at baseline and at weeks 4,6 and 10 of the trial using the Beck Anxiety Inventory(BAI) and Beck Depression Inventory(BDI) scales,respectively.Results:Mean BAI score was found to be significantly reduced following curcumin therapy(P=0.03).However,curcumin supplementation did not exert any significant impact on BDI scores(P=0.7).Conclusion:Curcumin has a potential anti-anxiety effect in individuals with obesity.

An Investigation of the Effects of Curcumin on Anxiety and Depression in Obese Individuals： A Randomized Controlled Trial

Ultrasmall platinum nanoparticles enable deep tumor penetration and synergistic therapeutic abilities through free radical species-assisted catalysis to combat cancer multidrug resistance

With the advent of nanotechnology, various modes of traditional treatment strategies have been transformed extensively owing to the advantageous morphological, physiochemical, and functional attributes of nano-sized materials, which are of particular interest in diverse biomedical applications, such as diagnostics, sensing, imaging, and drug delivery. Despite their success in delivering therapeutic agents, several traditional nanocarriers often end up with deprived selectivity and undesired therapeutic outcome, which significantly limit their clinical applicability. Further advancements in terms of improved selectivity to exhibit desired therapeutic outcome toward ablating cancer cells have been predominantly made focusing on the precise entry of nanoparticles into tumor cells via targeting ligands, and subsequent delivery of therapeutic cargo in response to specific biological or external stimuli. However, there is enough room intracellularly, where diverse small-sized nanomaterials can accumulate and significantly exert potentially specific mechanisms of antitumor effects toward activation of precise cancer cell death pathways that can be explored. In this review, we aim to summarize the intracellular pathways of nanoparticles, highlighting the principles and state of their destructive effects in the subcellular structures as well as the current limitations of conventional therapeutic approaches. Next, we give an overview of subcellular performances and the fate of internalized nanoparticles under various organelle circumstances, particularly endosome or lysosome, mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus, by comprehensively emphasizing the unique mechanisms with a series of interesting reports. Moreover, intracellular transformation of the internalized nanoparticles, prominent outcome and potential affluence of these interdependent subcellular components in cancer therapy are emphasized. Finally, we conclude with perspectives with a focus on the contemporary challenges in their clinical applicability.

/pdf/subcellular-performance-of-nanoparticles-in-cancer-therapy-2zonptxycq.pdf

Subcellular Performance of Nanoparticles in Cancer Therapy

In recent years, porous bioactive glass micro/nanospheres (PBGSs) have emerged as attractive biomaterials in various biomedical applications where such engineered particles provide suitable functions, from tissue engineering to drug delivery. The design and synthesis of PBGSs with controllable particle size and pore structure are critical for such applications. PBGSs have been successfully synthesized using melt-quenching and sol-gel based methods. The morphology of PBGSs is controllable by tuning the processing parameters and precursor characteristics during the synthesis. In this comprehensive review on PBGSs, we first overview the synthesis approaches for PBGSs, including both melt-quenching and sol-gel based strategies. Sol-gel processing is the primary technology used to produce PBGSs, allowing for control over the chemical compositions and pore structure of particles. Particularly, the influence of pore-forming templates on the morphology of PBGSs is highlighted. Recent progress in the sol-gel synthesis of PBGSs with sophisticated pore structures (e.g., hollow mesoporous, dendritic fibrous mesoporous) is also covered. The challenges regarding the control of particle morphology, including the influence of metal ion precursors and pore expansion, are discussed in detail. We also highlight the recent achievements of PBGSs in a number of biomedical applications, including bone tissue regeneration, wound healing, therapeutic agent delivery, bioimaging, and cancer therapy. Finally, we conclude with our perspectives on the directions of future research based on identified challenges and potential new developments and applications of PBGSs.

Porous bioactive glass micro- and nanospheres with controlled morphology: developments, properties and emerging biomedical applications

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.

/pdf/metal-species-encapsulated-mesoporous-silica-nanoparticles-4clzi0ms7v.pdf

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

Alzheimer's disease (AD), an age-related neurodegenerative disease, the most common causes of dementia is a multifactorial pathology categorized by a complex etiology. Numerous nutraceuticals have been clinically evaluated, but some of the trials failed. However, natural compounds have some limitations due to their poor bioavailability, ineffective capability to cross the blood-brain barrier, or less therapeutic effects on AD. To overcome these disadvantages, nanoparticle-conjugated natural products could promote the bioavailability and enhance the therapeutic efficacy of AD when compared with a naked drug. This application generates and implements new prospect for drug discovery in neurodegenerative diseases. In this article, we confer AD pathology, review natural products in clinical trials, and ascertain the importance of nanomedicine coupled with natural compounds for AD.

/pdf/nanoparticle-conjugated-nutraceuticals-exert-prospectively-3yo1qm79dc.pdf

Nanoparticle-conjugated nutraceuticals exert prospectively palliative of amyloid aggregation.

In this study, a methodology utilizing peptide conformational imprints (PCIs) as a tool to specifically immobilize porcine pancreatic alpha-trypsin (PPT) at a targeted position is demonstrated. Owing to the fabrication of segment-mediated PCIs on the magnetic particles (PCIMPs), elegant cavities complementary to the PPT structure are constructed. Based on the sequence on targeted PPT, the individual region of the enzyme is trapped with different template-derived PCIMPs to show certain types of inhibition. Upon hydrolysis, N-benzoyl-L-arginine ethyl ester (BAEE) is employed to assess the hydrolytic activity of PCIMPs bound to the trypsin using high-performance liquid chromatography (HPLC) analysis. Further, the kinetic data of four different PCIMPs are compared. As a result, the PCIMPs presented non-competitive inhibition toward trypsin, according to the Lineweaver-Burk plot. Further, the kinetic analysis confirmed that the best parameters of PPT/PCIMPs 233–245+G were Vmax = 1.47 × 10−3 mM s−1, Km = 0.42 mM, kcat = 1.16 s−1, and kcat/Km = 2.79 mM−1 s−1. As PPT is bound tightly to the correct position, its catalytic activities could be sustained. Additionally, our findings stated that the immobilized PPT could maintain stable activity even after four successive cycles.

https://www.mdpi.com/2079-4991/11/2/334/pdf

Deviation of Trypsin Activity Using Peptide Conformational Imprints.

Peptide conformational imprints (PCIs) offer a promising perspective to directly generate binding sites for preserving enzymes with high catalytic activity and stability. In this study, we synthesized a new chiral cross-linker cost-effectively for controlling the matrix morphology of PCIs on magnetic particles (PCIMPs) to stabilize their recognition capability. Meanwhile, based on the flank part of the sequences on papain (PAP), three epitope peptides were selected and synthesized. Molecularly imprinted polymers (MIPs) were then fabricated in the presence of the epitope peptide using our new cross-linker on magnetic particles (MPs) to generate PCIMPs. PCIMPs were formed with helical cavities that complement the PAP structure to adsorb specifically at the targeted position of PAP. PCIMPs65–79 were found to have the best binding parameters to the PAP with K d = 0.087 μM and B max = 4.56 μM. Upon esterification of N-Boc-His-OH, proton nuclear magnetic resonance (1H-NMR) was used to monitor the yield of the reaction and evaluate the activity of PAP/PCIMPs. The kinetic parameters of PAP/PCIMPs65–79 were calculated as V max = 3.0 μM s−1, K m = 5 × 10−2 M, k cat = 1.1 × 10–1 s−1, and k cat/K m = 2.2 M−1 s−1. In addition, PAP is bound tightly to PCIMPs to sustain its activity after four consecutive cycles.

/pdf/peptide-conformational-imprints-enhanced-the-catalytic-2vmymk96.pdf

Kiran Reddy Kanubaddi

Papers

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

Nanoparticle-conjugated nutraceuticals exert prospectively palliative of amyloid aggregation.

Deviation of Trypsin Activity Using Peptide Conformational Imprints.

Peptide conformational imprints enhanced the catalytic activity of papain for esterification