Lipid shape and packing are key for optimal design of pH-sensitive mRNA lipid nanoparticles.

The ionizable-lipid component of RNA-containing nanoparticles controls the pH-dependent behavior necessary for an efficient delivery of the cargo-the so-called endosomal escape. However, it is still an empirical exercise to identify optimally performing lipids. Here, we study two well-known ionizable lipids, DLin-MC3-DMA and DLin-DMA using a combination of experiments, multiscale computer simulations, and electrostatic theory. All-atom molecular dynamics simulations, and experimentally measured polar headgroup pKa values, are used to develop a coarse-grained representation of the lipids, which enables the investigation of the pH-dependent behavior of lipid nanoparticles (LNPs) through Monte Carlo simulations, in the absence and presence of RNA molecules. Our results show that the charge state of the lipids is determined by the interplay between lipid shape and headgroup chemistry, providing an explanation for the similar pH-dependent ionization state observed for lipids with headgroup pKa values about one-pH-unit apart. The pH dependence of lipid ionization is significantly influenced by the presence of RNA, whereby charge neutrality is achieved by imparting a finite and constant charge per lipid at intermediate pH values. The simulation results are experimentally supported by measurements of α-carbon 13C-NMR chemical shifts for eGFP mRNA LNPs of both DLin-MC3-DMA and DLin-DMA at various pH conditions. Further, we evaluate the applicability of a mean-field Poisson-Boltzmann theory to capture these phenomena.

Innovations in lymph node targeting nanocarriers.

Lymph nodes are secondary lymphoid tissues in the body that facilitate the co-mingling of immune cells to enable and regulate the adaptive immune response. They are also tissues implicated in a variety of diseases, including but not limited to malignancy. The ability to access lymph nodes is thus attractive for a variety of therapeutic and diagnostic applications. As nanotechnologies are now well established for their potential in translational biomedical applications, their high relevance to applications that involve lymph nodes is highlighted. Herein, established paradigms of nanocarrier design to enable delivery to lymph nodes are discussed, considering the unique lymph node tissue structure as well as lymphatic system physiology. The influence of delivery mechanism on how nanocarrier systems distribute to different compartments and cells that reside within lymph nodes is also elaborated. Finally, current advanced nanoparticle technologies that have been developed to enable lymph node delivery are discussed.

Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.

Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation. Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.

Laponite modified methacryloyl gelatin hydrogel with controlled release of vascular endothelial growth factor a for bone regeneration.

Reconstruction of bone defects has long been a major clinical challenge. Limited by the various shortcomings of conventional treatment like autologous bone grafting and inorganic substitutes, the development of novel bone repairing strategies is on top priority. Injectable biomimetic hydrogels that deliver stem cells and growth factors in a minimally invasive manner can effectively promote bone regeneration and thus represent a promising alternative. Therefore, in this study, we designed and constructed an injectable nanocomposite hydrogel co-loaded with Laponite (Lap) and vascular endothelial growth factor (VEGF) through a simplified and convenient scheme of physical co-mixing (G@Lap/VEGF). The introduced Lap not only optimized the injectability of GelMA by the electrostatic force between the nanoparticles, but also significantly delayed the release of VEGF-A. In addition, Lap promoted high expression of osteogenic biomarkers in mesenchymal stem cells (MSCs) and enhanced the matrix mineralization. Besides, VEGF-A exerted chemotactic effects recruiting endothelial progenitor cells (EPCs) and inducing neovascularization. Histological and micro-CT results demonstrated that the critical-sized calvarial bone defect lesions in the SD rats after treated with G@Lap/VEGF exhibited significant in vivo bone repairing. In conclusion, the injectable G@Lap/VEGF nanocomposite hydrogel constructed in our study is highly promising for clinical transformation and applications, providing a convenient and simplified scheme for clinical bone repairing, and contributing to the further development of the injectable biomimetic hydrogels.

Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality.

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice yield and quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm-2 and 11.0 t hm-2) and grain quality reaching the level of CK group. The adequate nitrogen supply in PCU group during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.

Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release.

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical-based transdermal drug delivery technologies for real-time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical-based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

O-nitrobenzyl Caged Molecule Enables Photo-controlled Release of Thiabendazole.

Pesticides are essential in agricultural development. Controlled-release pesticides have attracted great attentions. Base on a principle of spatiotemporal selectivity, we extended the photoremovable protective group (PRPG) into agrochemical agents to achieve controllable release of active ingredients. Herein, we obtained NP-TBZ by covalently linking o-nitrobenzyl (NP) with thiabendazole (TBZ). Compound NP-TBZ can be controlled to release TBZ in dependent to light. The irradiated and unirradiated NP-TBZ showed significant differences on fungicidal activities both in vitro and in vivo. In addition, the irradiated NP-TBZ displayed similar antifungal activities to the directly-used TBZ, indicating a factual applicability in controllable release of TBZ. Furthermore, we explored the action mode and microcosmic variations by SEM analysis, and demonstrated that the irradiated NP-TBZ retained a same action mode with TBZ against mycelia growth.

Dual pH and Ca2+-Responsive PEG-Modified Pillar[5]arene-Based Supramolecular Nanodrug Delivery System: Excellent Cargo Encapsulation and Minimal Drug Toxicity.

Chemotherapy is one of the most employed strategies in clinical treatment of cancer. However, reducing medication adverse effects and improving the biological activity remains a significant issue for chemotherapy. We developed a pH and Ca2+-responsive pillar[5]arene-based supramolecular nanodrug delivery system (NDDS) WP5⊃EV@DOX to address the aforementioned challenges. The formation of this NDDS began with the spontaneous formation of supramolecular nanodrug carrier WP5⊃EV in water from PEG-modified pillar[5]arene and the bipyridilium salt derivative EV through simple host-guest interaction. Then the antitumor drug doxorubicin DOX was efficiently loaded with a high encapsulation rate of 84.6 %. Cytotoxicity results indicated that the constructed nanoplatform not only reduced DOX toxicity and side effects on normal cell (293T), but also significantly enhanced the antitumor activity on cancer cell (HepG2). Moreover, in vivo experiments showed that WP5⊃EV@DOX had a longer half-life and higher bioavailability in the blood of mice compared to the nake drug DOX, with increases to 212 % and 179 %, respectively. Therefore, WP5⊃EV@DOX has great potential in tumor therapy and provides a new idea for host-guest drug delivery system.

Application of hydrogel microneedles in the oral cavity.

Microneedles are a transdermal drug delivery system in which the needle punctures the epithelium to deliver the drug directly to deep tissues, thus avoiding the influence of the first-pass effect of the gastrointestinal tract and minimizing the likelihood of pain induction. Hydrogel microneedles are microneedles prepared from hydrogels that have good biocompatibility, controllable mechanical properties, and controllable drug release and can be modified to achieve environmental control of drug release in vivo. The large epithelial tissue in the oral cavity is an ideal site for drug delivery via microneedles. Hydrogel microneedles can overcome mucosal hindrances to delivering drugs to deep tissues; this prevents humidity and a highly dynamic environment in the oral cavity from influencing the efficacy of the drugs and enables them to obtain better therapeutic effects. This article analyzes the materials and advantages of common hydrogel microneedles and reviews the application of hydrogel microneedles in the oral cavity.

Pharmacokinetic-Pharmacodynamic Analysis of pH-Responsive Doxorubicin-Releasing Micelles with Anticancer Activity.

This study aimed to investigate the effect of in vivo pH-responsive doxorubicin (DOX) release and the targetability of pilot molecules in folic acid (FA)-modified micelles using a pharmacokinetic-pharmacodynamic (PK-PD) model. The time profiles of intratumoral DOX concentrations in Walker256 tumor-bearing rats were monitored using a microdialysis probe, followed by compartmental analysis, to evaluate intratumoral tissue pharmacokinetics. Maximal DOX was released from micelles 350 min after the administration of pH-responsive DOX-releasing micelles. However, FA modification of the micelles shortened the time to peak drug concentration to 150 min. Additionally, FA modification resulted in a 27-fold increase in the tumor inflow rate constant. Walker256 tumor-bearing rats were subsequently treated with DOX, pH-responsive DOX-releasing micelles, and pH-responsive DOX-releasing FA-modified micelles to monitor the tumor growth-time profiles. An intratumoral threshold concentration of DOX (55-64 ng/g tumor) was introduced into the drug efficacy compartment to construct a PD model, followed by PK-PD analysis of the tumor growth-time profiles. Similar results of threshold concentration and drug potency of DOX were obtained across all three formulations. Cell proliferation was delayed as the drug delivery ability of DOX was improved. The PK model, which was developed using the microdialysis method, revealed the intratumoral pH-responsive DOX distribution profiles. This facilitated the estimation of intratumoral PK parameters. The PD model with threshold concentrations contributed to the estimation of PD parameters in the three formulations, with consistent mechanisms observed. We believe that our PK-PD model can objectively assess the contributions of pH-responsive release ability and pilot molecule targetability to pharmacological effects.

Tumoral Pharmacokinetic-Pharmacodynamic Simulation of Doxorubicin-Encapsulated Polymeric Micelles Using a Tissue-Isolated Tumor Perfusion System.

Pharmacokinetic (PK) elucidation of polymeric micelles delivering anticancer drugs is crucial for accurate antitumor PK-pharmacodynamic (PK-PD) simulations. Particularly, establishing a methodology to quantify the tumor inflow and outflow of anticancer drugs encapsulated in polymeric micelles is an essential challenge. General tumor biodistribution experiments are disadvantageous in that inflow quantification is easy, but outflow quantification is challenging. We addressed this issue by proposing a quantification method that combines a tissue-isolated tumor perfusion system with microdialysis. This method aims to determine tumoral drug inflow and outflow by quantifying the drugs released from the polymeric micelles via a tumor-embedded microdialysis probe and perfusate, respectively. Furthermore, we evaluated the feasibility of this method by perfusing pH-sensitive polyethylene glycol-poly(aspartate-hydrazone-doxorubicin/phenylalanine)n (PPDF-Hyd-DOX) in a tissue-isolated tumor perfusion system, and we quantified tumor inflow and outflow released DOX. Based on the quantitative results, we performed compartmental analyses by incorporating the gamma-distributed delay function and calculated the PK rate constants. These parameters were input into a tumor-bearing rat compartment model for ex vivo-in vivo extrapolation (EVIVE) of the rat plasma PPDF-Hyd-DOX concentrations and simulated intratumorally released DOX concentrations. The simulation profiles demonstrated a good fit with the Walker 256 intratumoral released DOX concentration profiles previously reported. This EVIVE-PK model was coupled with the threshold natural-growth tumor PD model, and PK-PD analysis was performed. This model exhibited a better fit to the tumor weight profile of Walker 256-bearing rats treated with PPDF-Hyd-DOX than that of our previously reported PK-PD model. Thus, EVIVE, based on a tissue-isolated tumor perfusion system with microdialysis, is a promising approach for the PK-PD simulation of polymeric micelle anticancer therapy.

Advancements in wound healing: integrating biomolecules, drug delivery carriers, and targeted therapeutics for enhanced tissue repair.

Wound healing, a critical biological process vital for tissue restoration, has spurred a global market exceeding $15 billion for wound care products and $12 billion for scar treatment. Chronic wounds lead to delayed or impaired wound healing. Natural bioactive compounds, prized for minimal side effects, stand out as promising candidates for effective wound healing. In response, researchers are turning to nanotechnology, employing the encapsulation of these agents into drug delivery carriers. Drug delivery system will play a crucial role in enabling targeted delivery of therapeutic agents to promote tissue regeneration and address underlying issues such as inflammation, infection, and impaired angiogenesis in chronic wound healing. Drug delivery carriers offer distinct advantages, exhibiting a substantial ratio of surface area to volume and altered physical and chemical properties. These carriers facilitate sustained and controlled release, proving particularly advantageous for the extended process of wound healing, that typically comprise a diverse range of components, integrating both natural and synthetic polymers. Additionally, they often incorporate bioactive molecules. Despite their properties, including poor solubility, rapid degradation, and limited bioavailability, various natural bioactive agents face challenges in clinical applications. With a global research, emphasis on harnessing nanomaterial for wound healing application, this research overview engages advancing drug delivery technologies to augment the effectiveness of tissue regeneration using bioactive molecules. Recent progress in drug delivery has poised to enhance the therapeutic efficacy of natural compounds in wound healing applications.

pH-sensitive and redox-responsive poly(tetraethylene glycol) nanoparticle-based platform for cancer treatment.

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle (NP) platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) NPs were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity (DLC), and drug loading efficiency (DLE). The impact of NPs on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) NPs. These NPs exhibit high DLE (78.7%) and DLC (12%), with minimal changes in particle size over time in different media.In vitroexperiments revealed that the NPs can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of NPs within cells. In conclusion, poly(tetraethylene glycol) NPs hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.

Micelles of poly[oligo(ethylene glycol) methacrylate] as delivery vehicles for zinc phthalocyanine photosensitizers.

Drug-loaded polymeric micelles have proven to be highly effective carrier systems for the efficient delivery of hydrophobic photosensitizers (PSs) in photodynamic therapy (PDT). This study introduces the micellization potential of poly(oligoethylene glycol methyl ether methacrylate) (pOEGMA) as a novel approach, utilizing the hydrophobic methacrylate segments of pOEGMA to interact with highly hydrophobic zinc phthalocyanine (ZnPc), thereby forming a potential micellar drug carrier system. The ZnPc molecule was synthesized from phthalonitrile derivatives and its fluorescence, photodegradation, and singlet oxygen quantum yields were determined in various solvents. In solvents such as tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide, the ZnPc compound exhibited the requisite photophysical and photochemical properties for PDT applications. The pOEGMA homopolymer was synthesized via reversible addition-fragmentation chain-transfer polymerization, while ZnPc-loaded pOEGMA micelles were prepared using the nanoprecipitation method. Characterization of the pOEGMA, ZnPc, and micelles was conducted using FTIR,1H-NMR, dynamic light scattering, matrix-assisted laser desorption/ionization time-of-flight mass spectrometries, gel permeation chromatography, and transmission electron microscopy. The critical micelle concentration was determined to be 0.027 mg ml-1using fluorescence spectrometry. The drug loading and encapsulation efficiencies of the ZnPc-loaded micelles were calculated to be 0.67% and 0.47%, respectively. Additionally, the release performance of ZnPc from pOEGMA micelles was monitored over a period of nearly 10 d, while the lyophilized micelles exhibited stability for 3 months. Lastly, the ZnPc-loaded micelles were more biocompatible than ZnPc on L929 cell line. The results suggest that the pOEGMA homopolymer possesses the capability to micellize through its methacrylate segments when interacting with highly hydrophobic molecules, presenting a promising avenue for enhancing the delivery efficiency of hydrophobic PSs in PDT. Moreover, it was also deciphered that obtained formulations were highly biocompatible according to cytotoxicity results and could be safely employed as drug delivery systems in further applications.

Technological Maturity of Aircraft-Based Methane Sensing for Greenhouse Gas Mitigation.

Methane is a major contributor to anthropogenic greenhouse gas emissions. Identifying large sources of methane, particularly from the oil and gas sectors, will be essential for mitigating climate change. Aircraft-based methane sensing platforms can rapidly detect and quantify methane point-source emissions across large geographic regions, and play an increasingly important role in industrial methane management and greenhouse gas inventory. We independently evaluate the performance of five major methane-sensing aircraft platforms: Carbon Mapper, GHGSat-AV, Insight M, MethaneAIR, and Scientific Aviation. Over a 6 week period, we released metered gas for over 700 single-blind measurements across all five platforms to evaluate their ability to detect and quantify emissions that range from 1 to over 1,500 kg(CH4)/h. Aircraft consistently quantified releases above 10 kg(CH4)/h, and GHGSat-AV and Insight M detected emissions below 5 kg(CH4)/h. Fully blinded quantification estimates for platforms using downward-facing imaging spectrometers have parity slopes ranging from 0.76 to 1.13, with R2 values of 0.61 to 0.93; the platform using continuous air sampling has a parity slope of 0.5 (R2 = 0.93). Results demonstrate that aircraft-based methane sensing has matured since previous studies and is ready for an increasingly important role in environmental policy and regulation.

Nanoparticle-mediated dsRNA delivery for precision insect pest control: a comprehensive review.

Nanoparticle-based delivery systems have emerged as powerful tools in the field of pest management, offering precise and effective means of delivering double-stranded RNA (dsRNA), a potent agent for pest control through RNA interference (RNAi). This comprehensive review aims to evaluate and compare various types of nanoparticles for their suitability in dsRNA delivery for pest management applications. The review begins by examining the unique properties and advantages of different nanoparticle materials, including clay, chitosan, liposomes, carbon, gold and silica. Each material's ability to protect dsRNA from degradation and its potential for targeted delivery to pests are assessed. Furthermore, this review delves into the surface modification strategies employed to enhance dsRNA delivery efficiency. Functionalization with oligonucleotides, lipids, polymers, proteins and peptides is discussed in detail, highlighting their role in improving stability, cellular uptake, and specificity of dsRNA delivery.This review also provides valuable guidance on choosing the most suitable nanoparticle-based system for delivering dsRNA effectively and sustainably in pest management. Moreover, it identifies existing knowledge gaps and proposes potential research directions aimed at enhancing pest control strategies through the utilization of nanoparticles and dsRNA.

Design, Synthesis, and Acid-Responsive Disassembly of Shell-Sheddable Block Copolymer Labeled with Benzaldehyde Acetal Junction.

Smart nanoassemblies degradable through the cleavage of acid-labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid-degradable shell-sheddable nanoassemblies. Herein, the authors report the synthesis and acid-responsive degradation through acid-catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid-labile linkage. The authors explore the synthesis and aqueous micellization of well-defined poly(ethylene glycol)-based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally-stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid-catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid-degradable shell-sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid-degradable shell-sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor-targeting drug delivery.