Nanodelivery System Research Articles

Ultrasound-Responsive Lipid Nanoplatform with Nitric Oxide and Carbon Monoxide Release for Cancer Sono-Gaso-Therapy.

Local gas therapy is emerging as a potential cancer treatment approach due to its specificity as gas-containing molecules can be packed into a nanodelivery system to release the corresponding gaseous molecules around the tumor site upon a suitable stimulus. Single-gas therapy has been reported, while synergistic dual-gas therapy has rarely been reported. Herein, we report a dual-gas-containing nanoplatform for synergistic cancer gasotherapy upon ultrasound irradiation. First, a robust ultrasound-responsive lipid-coated nanosystem was prepared with suitable particle size and characteristics. A low-intensity ultrasound (1.25 W/cm2) was found to simultaneously modulate carbon monoxide (CO) and nitric oxide (NO) release from the nanosystem in media and CT26 colon cancer cells for efficient therapeutic effect. The intracellular release promoted the overgeneration of reactive oxygen species (ROS) and triggered cancer cell apoptosis synergistically. The in vivo test demonstrated that the optimal dual-gas-containing formulation efficiently inhibited tumor growth (by ∼87%) at relatively low doses upon ultrasound irradiation (1.25 W/cm2, 5 min). This therapeutic efficacy shows that the current responsive lipid-coated delivery system has potential for ultrasound-triggered dual-gas therapy of both superficially and deeply seated cancers.

Design strategies of polysaccharide, protein and lipid-based nano-delivery systems in improving the bioavailability of polyphenols and regulating gut homeostasis.

Polyphenols are plant secondary metabolites that have attracted much attention due to their anti-inflammatory, antioxidant, and gut homeostasis promoting effects. However, food matrix interaction, poor solubility, and strong digestion and metabolism of polyphenols cause barriers to their absorption in the gastrointestinal tract, which further reduces bioavailability and limits polyphenols' application in the food industry. Nano-delivery systems composed of biocompatible macromolecules (polysaccharides, proteins and lipids) are an effective way to improve the bioavailability of polyphenols. Therefore, this review introduces the construction of biopolymer-based nano-delivery systems and their application in polyphenols, with emphasis on improving the solubility, stability, sustained release and intestinal targeting of polyphenols. In addition, there are possible positive effects of polyphenol-loaded nano-delivery systems on modulating gut microbiota and gut homeostasis, with particular emphasis on modulating intestinal inflammation, metabolic syndrome, and gut-brain axis. It is worth noting that the safety of bio-based nano-delivery systems still need to be further studied. In summary, the application of the bio-based nano-delivery system to deliver polyphenols provides insights for improving the bioavailability of polyphenols and for the treatment of potential diseases in the future.

Enhanced in vivo Stability and Antitumor Efficacy of PEGylated Liposomes of Paclitaxel Palmitate Prodrug.

The clinical use of paclitaxel (PTX) in cancer treatment is limited by its poor water solubility, significant toxicity, and adverse effects. This study aimed to propose a straightforward and efficient approach to enhance PTX loading and stability, thereby offering insights for targeted therapy against tumors. We synthesized a paclitaxel palmitate (PTX-PA) prodrug by conjugating palmitic acid (PA) to PTX and encapsulating it into liposomal vehicles using a nano delivery system. Subsequently, we investigated the in vitro and in vivo performance as well as the underlying mechanisms of PTX-PA liposomes (PTX-PA-L). PTX had a remarkable antitumor effect in vivo and significantly decreased the myelosuppressive toxicity of PTX. Moreover, the introduction of PA increased the lipid solubility of PTX, forming a phospholipid bilayer as a membrane stabilizer, prolonging the circulation time of the drug and indirectly increasing the accumulation of liposomes at the tumor site. Our in vivo imaging experiments demonstrated that PTX-PA-L labeled with DiR has greater stability in vivo than blank liposomes and that PTX-PA-L can target drugs to the tumor site and efficiently release PTX to exert antitumor effects. In a mouse model, the concentration of PTX at the tumor site in the PTX-PA-L group was approximately twofold greater than that of Taxol. However, in a nude mouse model, the concentration of PTX at the tumor site in the PTX-PA-L group was only approximately 0.8-fold greater than that of Taxol. Furthermore, the originally observed favorable pharmacodynamics in normal mice were reversed following immunosuppression. This may be caused by differences in esterase distribution and immunity. This prodrug technology combined with liposomes is a simple and effective therapeutic strategy with promising developmental prospects in tumor-targeted therapy owing to its ability to convert PTX into a long-circulating nano drug with low toxicity, high pharmacodynamics, and good stability in vivo.

Targeted delivery of Saikosaponin A and doxorubicin via hyaluronic acid-modified ZIF-8 nanoparticles for TNBC treatment: Inhibiting metastasis and reducing cardiotoxicity

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, making traditional hormone and targeted therapies ineffective. Chemotherapy remains the primary treatment for TNBC; however, it has failed to adequately address the high rates of recurrence and metastasis, underscoring the urgent need for new therapeutic strategies. This study investigates Saikosaponin A (SSA), a compound extracted from traditional Chinese medicine, for its potential to enhance the efficacy of doxorubicin (DOX) chemotherapy while reducing TNBC metastasis and mitigating DOX-induced cardiotoxicity.We first confirmed SSA's cardioprotective effects against DOX-induced cardiotoxicity, highlighting its potential as an adjunctive therapy for TNBC chemotherapy. Subsequently, through network pharmacology analysis, we identified that SSA may inhibit TNBC progression and metastasis by downregulating integrin β3, a key regulatory factor in tumor development. This was further validated through both in vivo and in vitro experiments. To address the poor bioavailability of SSA, we developed a novel drug delivery system utilizing hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for the co-delivery of SSA and DOX. This nano-drug system exhibited excellent stability and high drug-loading capacity, with loading efficiencies of 40.07 % for SSA and 43.07 % for DOX. After 24 h of nano-drug administration, the DOX concentration in the group using the nano-delivery system was 5.01 times higher than control group, demonstrated enhanced tumor-targeting capability. Furthermore, after 14 days of treatment, the tumor volume was reduced by 80.8 % compared to the control group, indicating significantly improved therapeutic efficacy (all P < 0.05).This study systematically evaluates the potential of this dual drug-loaded nanocarrier in improving TNBC treatment, reducing DOX-induced cardiotoxicity, and inhibiting metastasis, offering a novel therapeutic approach that integrates traditional medicine with advanced nanotechnology.

Peptide-functionalized polymeric nanoparticles for delivery of curcumin to cancer cells

Polymeric nanoparticles (NPs) have garnered significant interest due to their potential in drug delivery. Specifically, nanopolymers functionalized with molecules such as proteins or peptides serve as versatile vehicles for this purpose. Curcumin (Cur) is a widely studied anticancer compound known for its positive effects on human health. Nevertheless, its insolubility and low bio-distribution hinder the exploitation of its beneficial traits. In this study, our team developed a nanodelivery system using a nanopolymer called poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), functionalized with A6 peptide to enable targeted delivery of Cur. The designed system exhibited favorable characteristics, including a stable zeta potential of −13.8 mV, a small size of 76.4 nm, uniform surface morphology, and high hydrophilicity with a contact angle of 31.53°. Additionally, the targeted delivery system demonstrated high encapsulation efficiency (EE%) (93 ± 0.89 %), drug loading (DL%) (16.7 ± 0.9 %), and a slow and gradual release profile with a release of approximately 83.1 ± 0.12 %. The MTT assay results showed significant cell death in MDA-MB-231 cancer cells (IC50 = 21.3 ± 1.57 μM) when treated with the Cur-NPs-A6 formulation, while the toxicity of the designed NPs was reduced on non-cancerous MCF-10A cells. Moreover, both the RT-qPCR and invasion assays demonstrated the system's effectiveness in activating apoptosis pathways and inhibiting cell invasion. These findings suggest that the engineered intelligent delivery system, equipped with the A6 peptide, which has a strong affinity for CD44 (a protein with increased expression in malignancy), could be an exceptionally effective strategy for cancer treatment.

PH-responsive magnetic CuFe2O4-PMAA nanogel conjugated with amino-modified lignin for controlled breast cancer drug delivery

In this study, a novel magnetic and pH-responsive nanocarrier was developed, incorporating both natural and synthetic polymers, for delivering curcumin (CUR) to breast cancer cells. For this purpose, CuFe2O4@poly(methacrylic acid) (CuFe2O4@PMAA) nanogel was developed and conjugated with amino-modified lignin (Lignin-adipic acid dihydrazide conjugate, Lig-ADH) to achieve the CuFe2O4@PMAA@Lig-ADH nanocarrier. The morphology, structure, and physical properties of the synthesized nanomaterials were examined using a range of techniques, including transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), energy dispersive X-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized nanocarrier exhibited a spherical shape, with an average diameter of approximately 15 nm, and demonstrated good magnetic responsiveness. Moreover, the in vitro drug release was found to be pH-dependent, with an increased release rate in acidic conditions. To evaluate cytotoxicity, the survival of MCF-7 cells was measured using the MTT assay for 24 h. Notably, the synthesized CuFe2O4@PMAA@Lig-ADH@CUR and CUR exhibited significant cytotoxic effects, effectively eliminating MCF-7 cells with IC50 values of 39.80 µg/mL and 4.27 µg/mL, respectively. Also, the significant intracellular uptake of NPs was confirmed by FITC and DAPI staining after 4 h. This research highlighted the potential of CuFe2O4@PMAA@Lig-ADH@CUR as a highly effective nano-delivery system and demonstrated a straightforward method for utilizing renewable lignin.

Berberine-loaded PLGA nanoparticles alleviate ulcerative colitis by targeting IL-6/IL-6R axis

AimsThe present study aims to develop a nano-delivery system that encapsulates berberine (BBR) into PLGA-based nanoparticles (BPL-NPs), to treat ulcerative colitis (UC). Furthermore, the therapeutic efficacy and molecular targeting mechanisms of BPL-NPs in the management of UC are thoroughly examined.MethodsEmulsion solvent-driven methods were used to self-assemble BBR and PLGA into nanoparticles, resulting in the development of the nano-delivery system (BPL-NPs). The therapeutic effectiveness of BPL-NPs was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice and a lipopolysaccharide (LPS)-induced model of inflammation in THP-1 macrophages. The interaction between Mφs and NCM-460 cells was investigated using a co-culture system. The molecular targeting ability of BPL-NPs in the treatment of UC was validated through in vitro as well as in vivo experiments.ResultsThe BPL-NPs demonstrated a particle size of 184 ± 22.4 nm, enhanced dispersibility in deionized water, and a notable encapsulation efficiency of 31.1 ± 0.2%. The use of BPL-NPs clearly improved the clinical symptoms and pathological changes associated with UC in mice while also ensuring minimal toxicity. In addition, BPL-NPs improved intestinal epithelial cell apoptosis and enhanced the function of the intestinal barrier by inhibiting M1 Mφs infiltration and IL-6 signaling pathway in mice with UC. Furthermore, the BPL-NPs were found to selectively target the IL-6/IL-6R axis during the M1 Mφs-induced apoptosis of NCM460 cells.ConclusionThe BPL-NPs were confirmed to harbor anti-inflammatory effects both in vitro and in vivo, along with enhanced water solubility and bioactivity. In addition, the precise targeting of the IL-6/IL-6R axis was confirmed as the mechanism by which the BPL-NPs exerted therapeutic effects in UC, as demonstrated in both in vitro as well as in vivo studies.Graphical

An Effective Liposome-Based Nanodelivery System for Naphthalene Derivative Polyamines with Antitumor Activity

This study focuses on the development of a novel liposome-based nanodelivery system designed to encapsulate polyamine-1, a compound with potential anti-tumor properties. The main objective of this work was to enhance the therapeutic and imaging potential of polyamine-1 by incorporating it into liposome-based nanoparticles, which were functionalized with a gadolinium complex for imaging purposes and a fluorescent phospholipid for tracking applications. These nanoparticles were characterized by measuring their size, shape, polydispersity index, zeta potential and encapsulation efficiency. In vitro experiments were conducted to evaluate the antitumor activity, specifically determining the cytotoxicity of both free and encapsulated polyamine-1 in cancerous and non-cancerous cell lines. Additionally, the study shows the enhanced signal intensity of gadolinium-loaded liposomes by T1-weighted MRI, highlighting their imaging potential. The experimental results suggest that this liposome-based nanodelivery system not only has therapeutic potential in targeted cancer therapy but also could be advantageous for diagnostic imaging, particularly in MRI applications.

Human epidermal growth factor receptor 2(Her2)-targeted pH-responsive MR/NIRF bimodal imaging-mediated nano-delivery system for the diagnosis and treatment of undifferentiated thyroid cancer.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting. Drug delivery nanosystems can improve the efficiencies of drug in treating various cancer types. However, many conventional drug delivery nanosystems lack targeting and exhibit unresponsive drug release. Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs. This system targets human epidermal growth factor receptor 2 on the cell membrane surface of thyroid cancer cells and is designed to accumulate at tumor sites. Then, pH-responsive release of divalent manganese ions, ICG, and SRF enables magnetic resonance/fluorescence (MR/NIRF) dual-modality imaging and precise drug delivery for diagnostic and therapeutic integration. Various characterization analyses including transmission electron microscopy, Fourier infrared spectroscopy, and particle size analysis confirm that we successfully synthesized HISMP NPs with a diameter of 150.709nm. The results of CCK8 cytotoxicity and apoptosis assays show that HISMP NPs exhibited high cytotoxicity and induce apoptosis in thyroid cancer cells. In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.

Thiacloprid-silica nano-delivery system enhances toxicity against Aphis gossypii and improves non-target biosafety

Nanotechnology aligns with the requirements of sustainable development of agriculture, and nano-pesticides offer a promising approach to controlling agricultural pests and increasing productivity. Non-target predators also play a crucial role in pest controls and enhancing the efficacy of pesticide on target organisms. Reducing the toxicity of pesticides to non-target organisms is key to of coordinating chemical control and biological control methods. Therefore, it is essential to assess the toxicity of nano-pesticides on non-target predators. In this study, a carbon dots-doped mesoporous silica nano-delivery system (Thi@CD-MSN) was successfully developed using CD-MSN as carrier material and thiacloprid (Thi) as a model pesticide. The results demonstrated that the synthesized Thi@CD-MSN exhibited a relatively high loading efficiency (33.58%). Laboratory bioassay experiments revealed that Thi@CD-MSN demonstrated effective insecticidal activity (LC50 = 21.67 mg/L) in controlling Aphis gossypii Glover. Besides, the acute toxicity of Thi@CD-MSN on Chrysoperla pallens larvae was significantly lower than that of Thi, as was its toxicity to 4T1 cells. These findings suggest that CD-MSN can serve as an ecological safety carrier for pesticide delivery, improving the effective utilization of Thi while reducing the risks to non-target predators. These results are essential for comprehending the effects of nano-pesticides on non-target predators, providing informative data for implementing biological and chemical control strategies. It strengthens the safety evaluation of nano-pesticides.

Physical-Matched Nanoplatelets Boost Heterogeneous Thrombi Targeting Through Self-Adaptive Deformation for Thrombolysis and Endothelial Repairing.

The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins. The system exhibits progressive targeting, with the ability to target arterial and venous thrombosis and damaged blood vessels. D-PLT physically matches the pore structure of the thrombus by undergoing varied deformation, leading to advanced targeting and enrichment of arterial and venous thrombus. When co-loaded with the thrombolytic drug urokinase (UK) and the endothelium-protecting agent atorvastatin calcium (AT), the system improves rapid vascular opening of arterial and venous thrombosis in 90 min and provides up to 7 days of durable thrombolysis and recovery from endothelial dysfunction in vivo. This self-adaptive delivery system offers a promising strategy to overcome thrombus heterogeneity.

Assembly of niosomal nanodelivery system for iron: introducing a green-hybrid method to enhance encapsulation efficiency

Assembly of niosomal nanodelivery system for iron: introducing a green-hybrid method to enhance encapsulation efficiency

Salmon-IgM Functionalized-PLGA Nanosystem for Florfenicol Delivery as an Antimicrobial Strategy against Piscirickettsia salmonis.

Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, has been the most severe health concern for the Chilean salmon industry. The efforts to control P. salmonis infections have focused on using antibiotics and vaccines. However, infected salmonids exhibit limited responses to the treatments. Here, we developed a poly (D, L-lactide-glycolic acid) (PLGA)-nanosystem functionalized with Atlantic salmon IgM (PLGA-IgM) to specifically deliver florfenicol into infected cells. Polymeric nanoparticles (NPs) were prepared via the double emulsion solvent-evaporation method in the presence of florfenicol. Later, the PLGA-NPs were functionalized with Atlantic salmon IgM through carbodiimide chemistry. The nanosystem showed an average size of ~380-410 nm and a negative surface charge. Further, florfenicol encapsulation efficiency was close to 10%. We evaluated the internalization of the nanosystem and its impact on bacterial load in SHK-1 cells by using confocal microscopy and qPCR. The results suggest that stimulation with the nanosystem elicits a decrease in the bacterial load of P. salmonis when it infects Atlantic salmon macrophages. Overall, the IgM-functionalized PLGA-based nanosystem represents an alternative to the administration of antibiotics in salmon farming, complementing the delivery of antibiotics with the stimulation of the immune response of infected macrophages.

Photothermal Fe3O4 nanoparticles induced immunogenic ferroptosis for synergistic colorectal cancer therapy

Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA) in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H2O2. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8+ T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe3+, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.

Rational design of pH-responsive nano-delivery system with improved biocompatibility and targeting ability from cellulose nanocrystals via surface polymerization for intracellular drug delivery

Cellulose nanocrystals (CNCs), derived from diverse sources and distinguished by their inherent biodegradability, excellent biocompatibility, and facile cellular engulfment due to their rod-like structure, hold great promise as carriers for the development of nano-delivery systems. In this work, highly efficient rod-like CNCs were employed as substrates for grafting glycidyl onto their surfaces through ring-opening polymerization, forming hyperbranched polymers with superior cell uptake properties. Subsequently, 4-vinylbenzeneboronic acid (VB) and poly (ethylene glycol) methyl ether methacrylate (PEGMA) were employed as monomers in the polymerization process to fabricate a pH-responsive targeted nano-delivery system, denoted as CNCs-VB-PEGMA, via single electron transfer reactive radical polymerization (SET-LRP) reaction. The CNCs-VB-PEGMA was successfully prepared and used for the loading of curcumin (Cur) to form a pH-responsive nano-delivery system (CNCs-VB-PEGMA-Cur), and the loading rate of Cur was as high as 70.0 %. Studies showed that this drug delivery system could actively targeting liver cancer cells with the 2D cells model and 3D tumor microsphere model, showing efficient liver cancer cell-killing ability. Collectively, the CNCs-VB-PEGMA drug delivery system has potential applications in liver cancer therapy as an actively targeting and pH-responsive drug delivery system.

Characterization of CYP303A1 and its potential application based on ZIF-8 nanoparticle-wrapped dsRNA in Nilaparvata lugens (Stål).

RNA interference (RNAi) technology has been put forward as a promising method for pest control and resistance management. Mining highly efficient lethal genes and constructing stable double-stranded RNA (dsRNA) delivery systems are of great significance to improve the application potential of RNAi technology. In this study, we characterized a molting-related gene, NlCYP303A1, in Nilaparvata lugens that was highly expressed in the cuticle and at the end stages of each instar in nymphs. Silencing the expression of NlCYP303A1 in N. lugens resulted in a deformed phenotype and a significant increase in mortality. Furthermore, interfering with NlCYP303A1 changed the relative expression of key genes in the chitin synthesis and degradation pathway. Finally, we used the nanocarrier zeolitic imidazolate framework-8 (ZIF-8) to load dsNlCYP303A1, forming a complex denoted as dsNlCYP303A1@ZIF-8. The results of both feeding and rice-seedling dip experiments indicated that the expression of NlCYP303A1 was dramatically and persistently suppressed by the dsNlCYP303A1@ZIF-8 treatment, compared with treatment with dsNlCYP303A1, suggesting that ZIF-8 can enhance the interference efficiency as well as the stability of dsNlCYP303A1. Our results demonstrate that the lethal gene NlCYP303A1 can be employed as an excellent target for RNAi technology by loading onto a nano-delivery system, and provide new insights into the creation of innovative pest control approaches. © 2024 Society of Chemical Industry.

Enhanced Anti-Melanoma Activity of Nutlin-3a Delivered via Ethosomes: Targeting p53-Mediated Apoptosis in HT144 Cells.

This study evaluated ethosomes as a novel nanodelivery system for nutlin-3a, a known MDM2 inhibitor and activator of the p53 pathway, to improve nutlin-3a's poor solubility, limiting its bio-distribution and therapeutic efficacy. The potential of nutlin-3a-loaded ethosomes was investigated on two in vitro models of melanoma: the HT144 cell line p53wild-type and the SK-MEL-28 cell line p53mutated. Nutlin-3a-loaded ethosomes were characterized for their physicochemical properties and used to treat melanoma cells at different concentrations, considering nutlin-3a solution and empty ethosomes as controls. The biological effects on cells were evaluated 24 and 48 h after treatment by analyzing the cell morphology and viability, cell cycle, and apoptosis rate using flow cytometry and the p53 pathway's activation via Western blotting. The results indicate that ethosomes are delivery systems able to maintain nutlin-3a's functionality and specific biological action, as evidenced by the molecular activation of the p53 pathway and the biological events leading to cell cycle block and apoptosis in p53wild-type cells. Nutlin-3a-loaded ethosomes induced morphological changes in the HT144 cell line, with evident apoptotic cells and a reduction in the number of viable cells of over 80%. Furthermore, nutlin-3a-loaded ethosomes successfully modulated two p53-regulated proteins involved in survival/apoptosis, with up to a 2.5-fold increase in membrane TRAIL-R2 and up to an 8.2-fold decrease in Notch-1 (Notch intracellular domain, NICD) protein expression. The expression of these molecules is known to be altered or dysfunctional in a large percentage of melanoma tumors. Notably, ethosomes, regardless of their nutlin-3a loading, exhibited the ability to reduce HT144 melanoma cellular migration, as assessed in real time using xCELLigence, likely due to the modification of lipid rafts, suggesting their potential antimetastatic properties. Overall, nutlin-3a delivery using ethosomes appears to be a significantly effective means for upregulating the p53 pathway and downregulating active Notch-1, while also taking advantage of their unexpected ability to reduce cellular migration. The findings of this study could pave the way for the development of specific nutlin-3a-loaded ethosome-based medicinal products for cutaneous use.

Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T-DM1 demonstrates superior efficacy and tolerability, T-DM1-induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic-co-glycolic acid) (PLGA)nanoparticles as a delivery vehicle to conjugate T-DM1, aiming to alleviate T-DM1-induced thrombocytopenia. The T-DM1-conjugated PLGA nanoparticles (NPs-T-DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system

The aim of this study was to develop a sufficiently robust tetrandrine (Tet) nano-delivery system using acoustic resonance (AR) technology and freeze-drying technology. This system can effectively improve the solubility and dissolution properties of Tet, along with high stability and scale-up adaptability. Firstly, 54 stabilizers were screened simultaneously in a high-throughput manner with the help of AR technology to fully explore the optimal prescription space of tetrandrine nanosuspension (Tet-NS). The Plackett-Burman design was used to screen for critical variables severely affecting the quality of Tet-NS. The Box-Behnken design was used to investigate and optimize critical variables to obtain optimal nanosuspensions. The optimal prescription was successfully scaled up by 100 times, which was the initial exploration of its commercial scale production. Solidification studies have shown that formulations with 2.44% fructose as the cryoprotectant have excellent redispersibility. Compared with pure Tet, Tet in Tet-NS showed a significant increase in solubility and dissolution rate in water. Fourier transform infrared (FT-IR) demonstrated that no significant interactions occurred between the drug and excipients in Tet-NS. Powder x-ray diffraction analysis (PXRD) indicated that some of the Tet transformed into amorphous state during the preparation process. In short-term stability study, Tet-NS successfully maintained its physical stability. In summary, under the guidance of the QbD concept, this study rapidly developed Tet-NS using acoustic resonance technology, which can effectively improve the solubility and dissolution properties of Tet. During the development of Tet-NS, AR technology has demonstrated high particle size reduction capability, the ability to process multiple sets of formulations in parallel, and excellent scale-up capability. Meanwhile, the method and concept of this study are not limited to Tet, but also applicable to other poorly water-soluble drugs.

Nanoenabled Antiviral Pesticide for Tobacco Mosaic Virus: Excellent Adhesion Performance and Strong Inhibitory Effect to Alleviate the Damage on Photosynthetic System.

Tobacco mosaic virus (TMV) is a major agricultural threat. Here, a cationic star polymer (SPc) was designed to construct an efficient nanodelivery system for moroxydine hydrochloride (ABOB). ABOB could self-assemble with SPc via a hydrogen bond and van der Waals force, and this complexation reduced the particle size of ABOB from 2406 to 45 nm. With the aid of SPc, the contact angle of ABOB decreased from 100.8 to 79.0°, and its retention increased from 6.3 to 13.8 mg/cm2. Furthermore, the complexation with SPc could attenuate the degradation of ABOB in plants, and the bioactivity of SPc-loaded ABOB significantly improved with a reduction in relative viral expression from 0.57 to 0.17. The RNA-seq analysis revealed that the ABOB/SPc complex could up-regulate the expression of growth- and photosynthesis-related genes in tobacco seedlings, and the chlorophyll content increased by 2.5 times. The current study introduced an efficient nanodelivery system to improve the bioactivity of traditional antiviral agents.