Nanocarrier System For Delivery Research Articles

Nanoplatform based on carbon nanoparticles loaded with doxorubicin enhances apoptosis by generating reactive oxygen species for effective cancer therapy.

At present, due to its wide application and relatively low cost, chemotherapy remains a clinically important cancer treatment option; however, a number of chemotherapeutic drugs have important limitations, such as lack of specificity, high toxicity and side effects, and multi-drug resistance. The emergence of nanocarriers has removed numerous clinical application limitations of certain antitumor chemotherapy drugs and has been widely used in the treatment of tumors with nanodrugs. The present study used carbon nanoparticles (CNPs) as a nanocarrier for doxorubicin (DOX) to form the novel nanomedicine delivery system (CNPs@DOX)was demonstrated by UV-vis and fluorescence spectrophotometry, ζ potential and TEM characterization experiments. The results confirmed the successful preparation of CNPs@DOX nanoparticles with a particle size of 96±17 nm, a wide range of absorption and a negatively charged surface. Furthermore, CNPs@DOX produced more reactive oxygen species and induced apoptosis, and thus exhibited higher cytotoxicity than DOX, which is a small molecule anticancer drug without a nanocarrier delivery system.. The present study provides a strategy for the treatment of tumors with nanomedicine.

Gas-Phase Functionalization of Phytoglycogen Nanoparticles and the Role of Reagent Structure in the Formation of Self-Limiting Hydrophobic Shells.

A suite of acyl chloride structural isomers (C6H11OCl) was used to effect gas-phase esterification of starch-based phytoglycogen nanoparticles (PhG NPs). The surface degree of substitution (DS) was quantified using X-ray photoelectron spectroscopy, while the overall DS was quantified using 1H NMR spectroscopy. Gas-phase modification initiates at the NP surface, with the extent of surface and overall esterification determined by both the reaction time and the steric footprint of the acyl chloride reagent. The less sterically hindered acyl chlorides diffuse fully into the NP interior, while the branched isomers are restricted to the near-surface region and form self-limiting hydrophobic shells, with shell thicknesses decreasing with increasing steric footprint. These differences in substitution were also reflected in the solubility of the NPs, with water solubility systematically decreasing with increasing DS. The ability to separately control both the surface and overall degree of functionalization and thereby form thin hydrophobic shells has significant implications for the development of polysaccharide-based biopolymers as nanocarrier delivery systems.

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.Graphical abstract

Macrophage membrane (MMs) camouflaged near-infrared (NIR) responsive bone defect area targeting nanocarrier delivery system (BTNDS) for rapid repair: promoting osteogenesis via phototherapy and modulating immunity

Bone defects remain a significant challenge in clinical orthopedics, but no targeted medication can solve these problems. Inspired by inflammatory targeting properties of macrophages, inflammatory microenvironment of bone defects was exploited to develop a multifunctional nanocarrier capable of targeting bone defects and promoting bone regeneration. The avidin-modified black phosphorus nanosheets (BP-Avidin, BPAvi) were combined with biotin-modified Icaritin (ICT-Biotin, ICTBio) to synthesize Icaritin (ICT)-loaded black phosphorus nanosheets (BPICT). BPICT was then coated with macrophage membranes (MMs) to obtain MMs-camouflaged BPICT (M@BPICT). Herein, MMs allowed BPICT to target bone defects area, and BPICT accelerated the release of phosphate ions (PO43−) and ICT when exposed to NIR irradiation. PO43− recruited calcium ions (Ca2+) from the microenvironment to produce Ca3(PO4)2, and ICT increased the expression of osteogenesis-related proteins. Additionally, M@BPICT can decrease M1 polarization of macrophage and expression of pro-inflammatory factors to promote osteogenesis. According to the results, M@BPICT provided bone growth factor and bone repair material, modulated inflammatory microenvironment, and activated osteogenesis-related signaling pathways to promote bone regeneration. PTT could significantly enhance these effects. This strategy not only offers a solution to the challenging problem of drug-targeted delivery in bone defects but also expands the biomedical applications of MMs-camouflaged nanocarriers.Graphical

Aptamer-Targeted Dendrimersomes Assembled from Azido-Modified Janus Dendrimers "Clicked" to DNA.

Amphiphilic Janus dendrimers (JDs), synthetic alternatives to lipids, have the potential to expand the scope of nanocarrier delivery systems. JDs self-assemble into vesicles called dendrimersomes, encapsulate both hydrophobic cargo and nucleic acids, and demonstrate enhanced stability in comparison to lipid nanoparticles (LNPs). Here, we report the ability to enhance the cellular uptake of Janus dendrimersomes using DNA aptamers. Azido-modified JDs were synthesized and conjugated to alkyne-modified DNAs using copper-catalyzed azide alkyne cycloaddition. DNA-functionalized JDs form nanometer-sized dendrimersomes in aqueous solution via thin film hydration. These vesicles, now displaying short DNAs, are then hybridized to transferrin receptor binding DNA aptamers. Aptamer-targeted dendrimersomes show improved cellular uptake as compared to control vesicles via fluorescence microscopy and flow cytometry. This work demonstrates the versatility of using click chemistry to conjugate functionalized JDs with biologically relevant molecules and the feasibility of targeting DNA-modified dendrimersomes for drug delivery applications.

Clinical Potential of YY1-Hypoxia Axis for Vascular Normalization and to Improve Immunotherapy

Abnormal vasculature in solid tumors causes poor blood perfusion, hypoxia, low pH, and immune evasion. It also shapes the tumor microenvironment and affects response to immunotherapy. The combination of antiangiogenic therapy and immunotherapy has emerged as a promising approach to normalize vasculature and unlock the full potential of immunotherapy. However, the unpredictable and redundant mechanisms of vascularization and immune suppression triggered by tumor-specific hypoxic microenvironments indicate that such combination therapies need to be further evaluated to improve patient outcomes. Here, we provide an overview of the interplay between tumor angiogenesis and immune modulation and review the function and mechanism of the YY1-HIF axis that regulates the vascular and immune tumor microenvironment. Furthermore, we discuss the potential of targeting YY1 and other strategies, such as nanocarrier delivery systems and engineered immune cells (CAR-T), to normalize tumor vascularization and re-establish an immune-permissive microenvironment to enhance the efficacy of cancer therapy.

Self-Assembled Nanocarrier Delivery Systems for Bioactive Compounds.

Although bioactive compounds (BCs) have many important functions, their applications are greatly limited due to their own defects. The development of nanocarriers (NCs) technology has gradually overcome the defects of BCs. NCs are equally important as BCs to some extent. Self-assembly (SA) methods to build NCs have many advantages than chemical methods, and SA has significant impact on the structure and function of NCs. However, the relationship among SA mechanism, structure, and function has not been given enough attention. Therefore, from the perspective of bottom-up building mechanism, the concept of SA-structure-function of NCs is emphasized to promote the development of SA-based NCs. First, the conditions and forces for occurring SA are introduced, and then the SA basis and molecular mechanism of protein, polysaccharide, and lipid are summarized. Then, varieties of the structures formed based on SA are introduced in detail. Finally, facing the defects of BCs and how to be well solved by NCs are also elaborated. This review attempts to describe the great significance of constructing artificial NCs to deliver BCs from the aspects of SA-structure-function, so as to promote the development of SA-based NCs and the wide application of BCs.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

Different Approaches for Transdermal Nano-Carrier Delivery System

Transdermal drug delivery is a validated technology that makes a significant contribution to global pharmaceutical care. Since 1980, the sector has seen impressive growth with several commercial successes. The term transdermal drug delivery refers to the delivery of a drug across the layers of skin with the intention of allowing the drug to be absorbed through the skin in a predetermined and controlled rate manner. Skin is one of the largest organs that act as an efficient barrier for drug delivery. The present study focuses on the different approaches of nano-carrier system that delivers the nano-carrier drug across the skin barrier with the help of transdermal delivery system. Nano-carrier drug delivery systems are one of the biggest challenges to deliver drug into systemic circulation by crossing the skin barrier providing a passive drug delivery strategy that is known to be safer and faster than the conventional method. In this review, we describe the diverse types of nano-carriers approaches that have been synthesized for transdermal delivery system includes liposomes, niosomes, ethosomes, solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), polymeric nanoparticles, nanocrystals, nanofibers and nanosuspension/nanoemulsion. Several characterization methods of transdermal delivery system have been proposed to control the behavior of nano-carriers, along with in-vitro and in-vivo and other evaluation parameters. It was concluded that the compatibility of nano-carriers with the skin structure should be considered for transdermal nanocarrier delivery systems, which will be the most preferred route for drug delivery in the future as it offers high patient compliance, controlled dosing, low frequency of dosing, high physico-chemical stability and better dermal bioavailability, etc.

Recent Progress on Nanocarriers for Topical-Mediated RNAi Strategies for Crop Protection-A Review.

To fulfil the growing needs of the global population, sustainability in food production must be ensured. Insect pests and pathogens are primarily responsible for one-third of food losses and harmful synthetic pesticides have been applied to protect crops from these pests and other pathogens such as viruses and fungi. An alternative pathogen control mechanism that is more "friendly" to the environment can be developed by externally applying double-stranded RNAs (dsRNAs) to suppress gene expression. However, the use of dsRNA sprays in open fields is complicated with respect to variable efficiencies in the dsRNA delivery, and the stability of the dsRNA on and in the plants, and because the mechanisms of gene silencing may differ between plants and between different pathogen targets. Thus, nanocarrier delivery systems have been especially used with the goal of improving the efficacy of dsRNAs. Here, we highlight recent developments in nanoparticle-mediated nanocarriers to deliver dsRNA, including layered double hydroxide, carbon dots, carbon nanotubes, gold nanoparticles, chitosan nanoparticles, silica nanoparticles, liposomes, and cell-penetrating peptides, by review of the literature and patent landscape. The effects of nanoparticle size and surface modification on the dsRNA uptake efficiency in plants are also discussed. Finally, we emphasize the overall limitation of dsRNA sprays, the risks associated, and the potential safety concerns for spraying dsRNAs on crops.

A Triphenylphosphonium-Functionalized Delivery System for an ATM Kinase Inhibitor That Ameliorates Doxorubicin Resistance in Breast Carcinoma Mammospheres

The enzyme ataxia-telangiectasia mutated (ATM) kinase is a pluripotent signaling mediator which activates cellular responses to genotoxic and metabolic stress. It has been shown that ATM enables the growth of mammalian adenocarcinoma stem cells, and therefore the potential benefits in cancer chemotherapy of a number of ATM inhibitors, such as KU-55933 (KU), are currently being investigated. We assayed the effects of utilizing a triphenylphosphonium-functionalized nanocarrier delivery system for KU on breast cancer cells grown either as a monolayer or in three-dimensional mammospheres. We observed that the encapsulated KU was effective against chemotherapy-resistant mammospheres of breast cancer cells, while having comparably lower cytotoxicity against adherent cells grown as monolayers. We also noted that the encapsulated KU sensitized the mammospheres to the anthracycline drug doxorubicin significantly, while having only a weak effect on adherent breast cancer cells. Our results suggest that triphenylphosphonium-functionalized drug delivery systems that contain encapsulated KU, or compounds with a similar impact, are a useful addition to chemotherapeutic treatment schemes that target proliferating cancers.

The intracellular fate and transport mechanism of shape, size and rigidity varied nanocarriers for understanding their oral delivery efficiency

Nanocarriers have become an effective strategy to overcome epithelial absorption barriers. During the absorption process, the endocytosis mechanisms, cell internalization pathways, and transport efficiency of nanocarriers are greatly impacted by their physical properties. To understand the relationship between physical properties of nanocarriers and their abilities overcoming multiple absorption barriers, nanocarriers with variable physical properties were prepared via self-assembly of hydrolyzed α-lactalbumin peptide fragments. The impacts of size, shape, and rigidity of nanocarriers on epithelial cells endocytosis mechanisms, internalization pathways, transport efficiency, and bioavailability were studied systematically. The results showed that nanospheres were mainly internalized via clathrin-mediated endocytosis, which was then locked in lysosomes and degraded enzymatically in cytoplasm. While macropinocytosis was the primary pathway of nanotubes and transported to the endoplasmic reticulum and Golgi apparatus, resulting in a high drug concentration and sustained release in cytoplasm. Besides, nanotubes can overcome the multi-drug resistance by inhibiting the P-glycoprotein efflux. Furthermore, nanotubes can open intercellular tight-junctions instantaneously and reversibly, which promotes transport into blood circulation. The aqueous solubility of hydrophobic bioactive mangiferin (Mgf) was improved by nanocarriers. Most importantly, the bioavailability of Mgf was the highest for cross-linked short nanotube (CSNT) which outperformed free Mgf and other formulations by in vivo pharmacokinetic studies. Finally, Mgf-loaded CSNT showed an excellent therapeutic efficiency in vivo for the intervention of streptozotocin-induced diabetes. These results indicate that cross-linked α-lactalbumin nanotubes could be an effective nanocarrier delivery system for improving the epithelium cellular absorption and bioavailability of hydrophobic bioactive compounds.

Curcumin and N-Acetylcysteine Nanocarriers Alone or Combined with Deferoxamine Target the Mitochondria and Protect against Neurotoxicity and Oxidative Stress in a Co-Culture Model of Parkinson's Disease.

As the blood-brain barrier (BBB) prevents most compounds from entering the brain, nanocarrier delivery systems are frequently being explored to potentially enhance the passage of drugs due to their nanometer sizes and functional characteristics. This study aims to investigate whether Pluronic® F68 (P68) and dequalinium (DQA) nanocarriers can improve the ability of curcumin, n-acetylcysteine (NAC) and/or deferoxamine (DFO), to access the brain, specifically target mitochondria and protect against rotenone by evaluating their effects in a combined Transwell® hCMEC/D3 BBB and SH-SY5Y based cellular Parkinson's disease (PD) model. P68 + DQA nanoformulations enhanced the mean passage across the BBB model of curcumin, NAC and DFO by 49%, 28% and 49%, respectively (p < 0.01, n = 6). Live cell mitochondrial staining analysis showed consistent co-location of the nanocarriers within the mitochondria. P68 + DQA nanocarriers also increased the ability of curcumin and NAC, alone or combined with DFO, to protect against rotenone induced cytotoxicity and oxidative stress by up to 19% and 14% (p < 0.01, n = 6), as measured by the MTT and mitochondrial hydroxyl radical assays respectively. These results indicate that the P68 + DQA nanocarriers were successful at enhancing the protective effects of curcumin, NAC and/or DFO by increasing the brain penetrance and targeted delivery of the associated bioactives to the mitochondria in this model. This study thus emphasises the potential effectiveness of this nanocarrier strategy in fully utilising the therapeutic benefit of these antioxidants and lays the foundation for further studies in more advanced models of PD.

Tumor-targeting gene-photothermal synergistic therapies based on multifunctional polydopamine nanoparticles

Gene-photothermal synergistic therapy shows great potential for breast cancer treatment. Polydopamine (PDA) is a widely used photothermal therapeutic agent and delivery vector. Herein, a tumor-targeted nanoplatform of PDA grafted with PEG-g-PEI and folic acid (FA) (PPF) was elaborately fabricated for precisely intracellular delivery of microRNA-21 inhibitor (miR-21i). The multifunctional nanoplatform possessed a narrow size distribution, good stability, and excellent photothermal conversion efficiency. In vitro FA modification more effectively promoted the intracellular uptake of the nanocomposites by MCF-7 and 4T1 cells, and facilitated the miR-21i escape from the lysosomes, thus significantly inhibiting cell proliferation and inducing tumor cell apoptosis. More importantly, in vivo satisfactory tumor growth inhibition effects were observed in PPF/miR21 and laser co-treated group due to the near-infrared (NIR) responsive PDA and conjugated tumor-targeting FA. In conclusion, this nanocarrier delivery system exhibit enhanced anti-cancer effect, indicating the outstanding advantages of synergistic therapy by intergrating photothermal, gene, and accurate cancer-targeted treatment into one system, which will provide a valuable strategy for the clinical treatment of breast cancer.

Implementation of Quality by Design in the Formulation and Development of Nanocarrier-Based Drug Delivery Systems.

Quality by design (QbD) has recently fascinated researchers for utilizing it in various arenas of pharma trends. By overcoming the conventional process, QbD prevents the risk of errors caused by the 'guess and by god approach'. This framework fosters profound knowledge of product and process quality by implying sound science and risk assessment strategies. The virtue of QbD leads to the collaborative contribution to pharmaceutical industrialists and satisfies the regulatory bodies. Additionally, leading to rapid production, saves time and expenditure, tremendous versatility, provides immense knowledge, improves robustness, higher consistency, reduces user's dilemma, decreases certainty of failure, declining inter-batch variation in pharmaceutical development. In this ever-increasing continuous production world, regulatory organizations such as the U.S. Food & Drug Administration and the International Conference on Harmonization recommend Q8 to Q14 guidelines in order to obtain the desired quality product. This review extensively discusses on various approaches of QbD for the pharmaceutical development of nano-carrier drug delivery systems. Additionally, QbD's applications in process and analytical method development techniques are documented.

Stimuli-responsive nanocarrier delivery systems for Pt-based antitumor complexes: a review.

Platinum-based anticancer drugs play a crucial role in the clinical treatment of various cancers. However, the application of platinum-based drugs is heavily restricted by their severe toxicity and drug resistance/cross resistance. Various drug delivery systems have been developed to overcome these limitations of platinum-based chemotherapy. Stimuli-responsive nanocarrier drug delivery systems as one of the most promising strategies attract more attention. And huge progress in stimuli-responsive nanocarrier delivery systems of platinum-based drugs has been made. In these systems, a variety of triggers including endogenous and extracorporeal stimuli have been employed. Endogenous stimuli mainly include pH-, thermo-, enzyme- and redox-responsive nanocarriers. Extracorporeal stimuli include light-, magnetic field- and ultrasound responsive nanocarriers. In this review, we present the recent advances in stimuli-responsive drug delivery systems with different nanocarriers for improving the efficacy and reducing the side effects of platinum-based anticancer drugs.

Improvement in therapeutic activity and stability of neuropeptide Y using PEGylated polyplexes in MCF-7 and MDA-MB-231 cells

The transport of peptides and nucleic acid using polyplexes as carrier system shows potential in the gene and DNA-based delivery systems to treat various conditions such as infection, inflammation, cancer, etc. The present study focused on the development of neuropeptide Y-loaded polyplexes from cationic polymer coated with PEG 2000 by application of microfluidics. The PEGylated polyplexes were statistically optimized by 3-Level factorial design with entrapment efficiency of 87.06±6.15% and in-vitro release of neuropeptide Y of 83.71±6.31% for 24 h. These polyplexes displayed 15.5% of α-helical content with no shift in the β-sheet content from Reed reference using circular dichroism spectroscopy. The FTIR and NMR studies confirmed the polymeric reaction with neuropeptide Y in PEGylated polyplexes by displaying the presence of PEG-NHS interaction with PEG-PEI grafting. The formulation PPN showed G0G1 cell arrest with an IC 50 value of 4.98±0.5 μg/mL and 54.46±6.33% apoptosis on the MCF-7 and IC 50 value of 6.23±2.11 μg/mL and 50.23±5.71% apoptosis on MDA-MD-231 cells by upregulating phosphor-p38 MAPK pathway. The PEGylated polyplexes were found to be stable for 6 months and displayed particle size 360.52 ± 8.35 nm at 5°C and 368.02 ± 7.36 nm at 25°C due to formation of steric shield by PEGylation on the structures of polyplexes. The animals study showed no toxicity on administration of formulation PPN via intravenous route and better t 1/2 (5.79 h) and AUC (84888.63 pg/mL*min) without mortality. Hence, PEGylated polyplexes emerge as a novel, effective and economical nanocarrier delivery system contributing towards long-term stability, less toxicity with significant apoptotic action on breast cancer cell lines.

NANO CARRIER DRUG DELIVERY SYSTEMS FOR THE TREATMENT OF COGNITIVE DYSFUNCTION IN DEPRESSION-AN OVERVIEW ON THE NANO FORMULATIONS TARGETING TO THE BRAIN

To review and discuss the current therapeutic strategies available for the management of cognitive dysfunction in major depressive disorder with special emphasis on novel therapeutics based on nanotechnology like nano carrier delivery systems. The method entailed a review of research articles, review articles, and other internet-sourced materials. Journals, articles, and reports were thoroughly searched for the efficacy and safety of nanotechnology based newer drug delivery approaches for the management of cognitive dysfunction in major depressive disorder. The information obtained during the literature search aided in comprehending the scenario. Several new nanomedicines and nanotechnology based drug delivery systems for improving the efficacy of new and old drugs used for the management of cognitive dysfunction in major depressive disorder were reviewed. There is a dearth of sufficient studies which focus on cognitive domain in depression. Nanomedicines and nanotechnology based drug delivery systems holds tremendous potential in the management of cognitive impairment in depression as well as other neuropsychiatric disorders. It is imperative to conduct advanced studies in this regard for better therapeutic outcomes in the management of such patients.

Biopharmaceutical nanoclusters: Towards the self-delivery of protein and peptide therapeutics.

Protein and peptide biopharmaceuticals have had a major impact on the treatment of a number of diseases. There is a growing interest in overcoming some of the challenges associated with biopharmaceuticals, such as rapid degradation in physiological fluid, using nanocarrier delivery systems. Biopharmaceutical nanoclusters (BNCs) where the therapeutic protein or peptide is clustered together to form the main constituent of the nanocarrier system have the potential to mimic the benefits of more established nanocarriers (e.g., liposomal and polymeric systems) whilst eliminating the issue of low drug loading and potential side effects from additives. These benefits would include enhanced stability, improved absorption, and increased biopharmaceutical activity. However, the successful development of BNCs is challenged by the physicochemical complexity of the protein and peptide constituents as well as the dynamics of clustering. Here, we present and discuss common methodologies for the synthesis of therapeutic protein and peptide nanoclusters, as well as review the current status of this emerging field.

A Star Polyamine-Based Nanocarrier Delivery System for Enhanced Avermectin Contact and Stomach Toxicity against Green Peach Aphids.

The unscientific application of synthesized/botanical pesticides has not only brought the resistance of plant pathogens and pests, but also led to serious environmental pollution. In recent years, various nano-delivery systems have been used for the development of environmental-friendly pesticides with improved efficacy. Herein, the current study constructed an efficient avermectin B1a (AVM) nano-delivery system based on a star polyamine (SPc) and focused on the characterization and bioactivity of SPc-loaded AVM at various mass ratios. The hydroxyl groups of AVM could assemble with carbonyl groups of SPc through hydrogen bond and van der Waals forces, and the self-assembly of AVM and SPc formed nearly spherical particles of AVM/SPc complex with nanoscale size. The contact angle of SPc-loaded AVM decreased with the increasing mass ratio of SPc, revealing the easier distribution and spreading of the AVM/SPc complex. Furthermore, the stomach and contact toxicity of AVM/SPc complex also increased along with the increasing SPc mass ratio, which could be attributed to the enhanced systemic transportation in plants, enlarged contact area to insect pests and stronger permeability across the insect cuticle. The current study provides an efficient nano-delivery system for increasing stomach and contact toxicity of pesticides with wide applications in the agricultural field.