Alzheimer\'s disease (AD) poses a significant burden on the economy and healthcare systems worldwide. Although the pathophysiology of AD remains debatable, its progression is strongly correlated with the accumulation of tau aggregates. Therefore, tau clearance from brain lesions can be a promising strategy for AD therapy. To achieve this, the present study combined proteolysis-targeting chimera (PROTAC), a novel protein-degradation technique that mediates degradation of target proteins via the ubiquitin-proteasome system, and a neurotransmitter-derived lipidoid (NT-lipidoid) nanoparticle delivery system with high blood-brain barrier-penetration activity, to generate a novel nanomedicine named NPD. Peptide 1, a cationic tau-targeting PROTAC is loaded onto the positively charged nanoparticles using DNA-intercalation technology. The resulting nanomedicine displayed good encapsulation efficiency, serum stability, drug release profile, and blood-brain barrier-penetration capability. Furthermore, NPD potently induced tau clearance in both cultured neuronal cells and the brains of AD mice. Moreover, intravenous injection of NPD led to a significant improvement in the cognitive function of the AD mice, without any remarkable abnormalities, thereby supporting its clinical development. Collectively, the novel nanomedicine developed in this study may serve as an innovative strategy for AD therapy, since it effectively and specifically induces tau protein clearance in brain lesions, which in turn enhances cognition.

Most organophosphates (OPs) are hydrophobic, and after exposure, can sequester into lipophilic regions within the body, such as adipose tissue, resulting in long term chronic effects. Consequently, there is an urgent need for therapeutic agents that can decontaminate OPs in these hydrophobic regions. Accordingly, an enzyme-polymer surfactant nanocomplex is designed and tested comprising chemically supercharged phosphotriesterase (Agrobacterium radiobacter; arPTE) electrostatically conjugated to amphiphilic polymer surfactant chains ([cat.arPTE][S-]). Experimentally-derived structural data are combined with molecular dynamics (MD) simulations to provide atomic level detail on conformational ensembles of the nanocomplex using dielectric constants relevant to aqueous and lipidic microenvironments. These show the formation of a compact admicelle pseudophase surfactant corona under aqueous conditions, which reconfigures to yield an extended conformation at a low dielectric constant, providing insight into the mechanism underpinning cell membrane binding. Significantly, it demonstrated that [cat.arPTE][S-] spontaneously binds to human mesenchymal stem cell membranes (hMSCs), resulting in on-cell OP hydrolysis. Moreover, the nanoconstruct can endocytose and partition into the intracellular fatty vacuoles of adipocytes and hydrolyze sequestered OP.

UNASSIGNED: Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.
UNASSIGNED: Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.
UNASSIGNED: As a result, the optimized PNCs showed 3-fold encapsulation (<90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.
UNASSIGNED: Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods.

RNA interference (RNAi)-based biopesticides offer an attractive avenue for pest control. Previous studies revealed high RNAi sensitivity in Holotrichia parallela larvae, showcasing its potential for grub control. In this study, we aimed to develop an environmentally friendly RNAi method for H. parallela larvae. The double-stranded RNA (dsRNA) of the V-ATPase-a gene (HpVAA) was loaded onto layered double hydroxide (LDH). The dsRNA/LDH nanocomplex exhibited increased environmental stability, and we investigated the absorption rate and permeability of dsRNA-nanoparticle complexes and explored the RNAi controlling effect. Silencing the HpVAA gene was found to darken the epidermis of H. parallela larvae, with growth cessation or death or mortality, disrupting the epidermis and midgut structure. Quantitative reverse transcription-polymerase chain reaction and confocal microscopy confirmed the effective absorption of the dsRNA/LDH nanocomplex by peanut plants, with distribution in roots, stems, and leaves. Nanomaterial-mediated RNAi silenced the target genes, leading to the death of pests. Therefore, these findings indicate the successful application of the nanomaterial-mediated RNAi system for underground pests, thus establishing a theoretical foundation for developing a green, safe, and efficient pest control strategy.

The application of nanotechnology in biological and medical fields have resulted in the creation of new devices, supramolecular systems, structures, complexes, and composites. Dendrimers are relatively new nanotechnological polymers with unique features; they are globular in shape, with a topological structure formed by monomeric subunit branches diverging to the sides from the central nucleus. This review analyzes the main features of dendrimers and their applications in biology and medicine regarding cancer treatment. Dendrimers have applications that include drug and gene carriers, antioxidant agents, imaging agents, and adjuvants, but importantly, dendrimers can create complex nanosized constructions that combine features such as drug/gene carriers and imaging agents. Dendrimer-based nanosystems include different metals that enhance oxidative stress, polyethylene glycol to provide biosafety, an imaging agent (a fluorescent, radioactive, magnetic resonance imaging probe), a drug or/and nucleic acid that provides a single or dual action on cells or tissues. One of major benefit of dendrimers is their easy release from the body (in contrast to metal nanoparticles, fullerenes, and carbon nanotubes), allowing the creation of biosafe constructions. Some dendrimers are already clinically approved and are being used as drugs, but many nanocomplexes are currently being studied for clinical practice. In summary, dendrimers are very useful tool in the creation of complex nanoconstructions for personalized nanomedicine. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Acute myeloid leukemia carrying FMS-like tyrosine kinase receptor-3 (FLT3) mutations is a fatal blood cancer with a poor prognosis. Although the FLT3 inhibitor gilteritinib has recently been approved, it still suffers from limited efficacy and relatively high nonresponse rates. In this study, we report the potentiation of gilteritinib efficacy using nanocomplexation with a hyaluronic acid-epigallocatechin gallate conjugate. The self-assembly, colloidal stability, and gilteritinib loading capacity of the nanocomplex were characterized by reversed-phase high-performance liquid chromatography and dynamic light scattering technique. Flow cytometric analysis revealed that the nanocomplex efficiently internalized into FLT3-mutated leukemic cells via specific interactions between the surface-exposed hyaluronic acid and CD44 receptor overexpressed on the cells. Moreover, this nanocomplex was found to induce an eradication of the leukemic cells in a synergistic manner by elevating the levels of reactive oxygen species and caspase-3/7 activities more effectively than free gilteritinib. This study may provide a useful strategy to design nanomedicines capable of augmenting the therapeutic efficacy of FLT3 inhibitors for effective leukemia therapy.

This study was carried out to improve the stability of anthocyanins (ACNs) by developing MA-SC-KGM nanoparticles using a self-assembly method that involved the combination of sodium caseinate (SC) and konjac glucomannan (KGM) with mulberry anthocyanin extract (MA). Atomic force microscopy (AFM) analysis showed SC encapsulated MA successfully. Multispectral techniques demonstrated the presence of hydrogen bonds and hydrophobic interactions in the nanoparticles. MA-SC-KGM ternary mixture improved storage stability, color stability and anthocyanin retention better compared to the MA-SC binary mixture. Notably, MA-SC-KGM nanoparticles significantly inhibited the thermal degradation of ACNs, improved pH stability, and showed stability and a slow-release effect in gastrointestinal digestion experiments. In addition, MA-SC-KGM nanoparticles were effective in scavenging DPPH· and ABTS+ free radicals, with enhanced stability and antioxidant capacity even during the heating process. This study successfully developed a novel MA-SC-KGM protein-polysaccharide composite material that effectively stabilized natural ACNs, expanding the application of ACNs in various industries.

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.

Introduction: Breast cancer is a significant cause of mortality in women globally, and current treatment approaches face challenges due to side effects and drug resistance. Nanotechnology offers promising solutions by enabling targeted drug delivery and minimizing toxicity to normal tissues. Methods: In this study, we developed a composite platform called (Alg-AgNPs-CisPt), consisting of silver nanoparticles coated with an alginate hydrogel embedding cisplatin. We examined the effectiveness of this nanocomplex in induce synergistic cytotoxic effects on breast cancer cells. Results and Discussion: Characterization using various analytical techniques confirmed the composition of the nanocomplex and the distribution of its components. Cytotoxicity assays and apoptosis analysis demonstrated that the nanocomplex exhibited greater efficacy against breast cancer cells compared to AgNPs or cisplatin as standalone treatments. Moreover, the nanocomplex was found to enhance intracellular reactive oxygen species levels, further validating its efficacy. The synergistic action of the nanocomplex constituents offers potential advantages in reducing side effects associated with higher doses of cisplatin as a standalone treatment. Overall, this study highlights the potential of the (Alg-AgNPs-CisPt) nanocomplex as a promising platform embedding components with synergistic action against breast cancer cells.

A self-assembled peptides-calcium-Vitamin D3 ternary delivery system (CSPH-Ca-VD3) was prepared to investigate the promotion of cellular calcium transport. The constructed CSPH-Ca-VD3 nanocomplex exhibited a spherical structure with a size of 135.2 ± 10.2 nm. Based on the thermodynamic calculation of fluorescent spectra, hydrophobic interaction was shown as the major driving force for this nanocomplex structure. CSPH-Ca-VD3 nanocomplex possessed excellent stability during simulated gastrointestinal digestion, contributing to the prevention of acid degradation of VD3 and the enhancement of calcium solubility. Furthermore, the calcium transport efficiency in the form of CSPH-Ca-VD3 (4 mg/mL) across a Caco-2 cells monolayer was significantly increased 2.3-fold compared to that of free Ca2+, mainly attributed to the upregulation in the presence of CSPH-Ca-VD3 of TRPV6, calbindin D9k and PMCA1b expression in Caco-2 cells. The present study provided a basis for developing a novel delivery system of peptides-calcium chelate with the dual effects of VD3 protection and calcium uptake promotion.