Nano Drug Research Articles

Codelivery of dihydroartemisinin and chlorin e6 by copolymer nanoparticles enables boosting photodynamic therapy of breast cancer with low-power irradiation.

Given that chemotherapy as a stand-alone therapeutic strategy may not be sufficient to effectively treat cancer, there is increasing interest in combination of chemotherapy and alternative therapies. Photodynamic therapy has the advantages of high selectivity and low side effects, so the combination of photodynamic therapy and chemotherapy has become one of the most appealing strategies for tumor treatment. In this work, we constructed a nano drug codelivery system (PPDC) to realize the combined treatment of chemotherapy and photodynamic therapy through encapsulating chemotherapeutic drug dihydroartemisinin and photosensitizer chlorin e6 in PEG-PCL. The potentials, particle size and morphology of nanoparticles were characterized by dynamic light scattering and transmission electron microscopy. We also investigated the reactive oxygen species (ROS) generation and drug release ability. The antitumor effect in vitro was investigated by methylthiazolyldiphenyl-tetrazolium bromide assays and cell apoptosis experiments, and the potential cell death mechanisms were explored by ROS detection and Western blot analysis. The in vivo antitumor effect of PPDC was evaluated under the guidance of fluorescence imaging. Our work provides a potential antitumor treatment approach and expands the application of dihydroartemisinin for breast cancer therapy.

N-acetyl-L-cysteine attenuated the toxicity of ZIF-8 on EA.hy926 endothelial cells by wnt/β-catenin pathway

As kinds of porous crystalline compounds, zeolitic imidazolate frameworks (ZIFs) have been developed quickly and attracted considerable attention for use in nano drug delivery systems, which raised concerns about cardiovascular disorders. At the present, the cytotoxic mechanism of ZIFs in cardiovascular disorders was still unclear. Our experiment explored the toxicity of ZIF-8, a typical kind of ZIFs, on human EA.hy926 vascular endothelial cells. The cell viability, ROS formation, apoptosis level, inflammatory response level, wound healing ability and atherosclerosis-related indicators of EA.hy926 endothelial cells were analyzed after ZIF-8 treatment. Meanwhile, we evaluated the ability of antioxidant N-Acetyl-L-cysteine (NAC) to attenuate the toxicity of ZIF-8 on EA.hy926 endothelial cells. As results, NAC attenuated ROS formation, cell apoptosis, LDH formation and endothelial dysfunction caused by ZIF-8. As the Wnt/β-catenin pathway was involved in endothelial cell dysfunction, we also studied the expression level of β-catenin and LEF1 in ZIF-8 and/or NAC treated EA.hy926 cells. As expected, ZIF-8 increased the protein expressions of β-catenin and LEF1in the IC50 group, which was significantly inhibited by co-treatment with NAC. Taken together, this study could help improve our understanding about the mechanism of ZIF-8-induced endothelial cells injury and NAC had therapeutic potential in preventing ZIF-8-associated endothelial dysfunction by wnt/β-catenin pathway.

Nano Delivery of Chemotherapeutic ICD Inducers for Tumor Immunotherapy.

Immunogenic cell death (ICD, also known as immunogenic apoptosis) of malignant cells is confirmed to activate the host immune system to prevent, control, and eliminate tumors. Recently, a range of chemotherapeutic drugs have been repurposed as ICD inducers and applied for tumor immunotherapy. However, several hurdles to the widespread application of chemotherapeutic ICD inducers remain, namely poor water solubility, short blood circulation, non-specific tissue distribution, and severe toxicity. Recent advances in nanotechnology and pharmaceutical formulation foster the development of nano drug delivery systems to tackle the aforementioned hurdles and expedite safe, effective, and specific delivery. This review will describe delivery barriers to chemical ICD inducers and highlight recent nanoformulations for these drugs in tumor immunotherapy.

Recent advances in drug delivery systems for targeting brain tumors

Brain tumor accounts for about 1.6% of incidence and 2.5% of mortality of all tumors, and the median survival for brain tumor patients is only about 20 months. The treatment for brain tumor still faces many challenges, such as the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), the overexpressed efflux pumps, the infiltration, invasion, high heterogeneity of tumor cells, drug resistance and immune escape caused by tumor microenvironment (TME) and cancer stem cells (CSC). This review attempts to clarify the challenges for multi-functional nano drug delivery systems (NDDS) to cross the BBB and target the cancer cells or organelles, and also provides a brief description of the different types of targeted multi-functional NDDS that have shown potential for success in delivering drugs to the brain. Further, this review also summarizes the research progress of multi-functional NDDS in the combination therapy of brain tumors from the following sections, the combination of chemotherapy drugs, chemotherapy-chemodynamic combination therapy, chemotherapy-immunization combination therapy, and chemotherapy-gene combination therapy. We also provide an insight into the recent advances in designing multi-functional NDDS for combination therapy.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

Research Progress of Functional Nano Drug Carrier Puerarin in The Treatment of Skin Diseases

Functional nanofibers have good porosity to exchange oxygen and appropriate surface hydrophilicity to promote cell adhesion and proliferation, which has attracted extensive attention in the medical research field in the treatment of skin repair diseases. Puerarin is a kind of isoflavones extracted from the roots of the leguminous plant pueraria lobata or kudzu vine. Because of its strong antioxidant, free radical scavenging and anti-tumor effects, puerarin has made some preliminary exploration in the research field of skin diseases in recent years. This paper summarizes the research progress of skin wound repair, puerarin treatment of skin diseases and nanotechnology in skin wound repair, with a view to providing new therapeutic ideas for the research and development of puerarin skin wound repair.

Selection of an aggregation-caused quenching-based fluorescent tracer for imaging studies in nano drug delivery systems.

In order to develop and optimize nano drug delivery systems (NDDSs), it is crucial to understand their in vivo fate. We previously found that P2 (Aza-BODIPY) and P4 (BODIPY) as aggregation-caused quenching (ACQ) probes could be used to unravel the biofate of various nanoparticles owing to their water-sensitive emission. However, previous studies also found that quenched ACQ probe aggregates showed repartition into hydrophobic physiologically relevant constituents, resulting in fluorescence re-illumination. In this paper, we screened various types of fluorophores for ACQ and their re-illumination performance and focused on Aza-BODIPY dyes. BODIPY and Aza-BODIPY dyes were identified to be advantageous over other fluorophores. Some BODIPY and Aza-BODIPY dyes were selected as potential probes with improved performance against re-illumination. The best performing probes were Aza-C7 and Aza-C8. Aza-C7-loaded PMs were found to have decreased fluorescence re-illumination properties over P2 and DiR.

Evaluating the Efficacy of Polyglycolic Acid-Loading Tetrandrine Nanoparticles in the Treatment of Dry Eye

Introduction: Dry eye disease (DED) is a multifactor-induced disease accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Traditional anti-inflammation agent corticosteroids applied in DED treatment could result in high intraocular pressure, especially in long-term treatment. Therefore, we explored a nano drug that aimed to block the formation pathway of DED which had anti-inflammatory, sustained release, and good biocompatibility characteristics in this study. Methods: We prepared a novel nanomedicine (Tet-ATS@PLGA) by the thin film dispersion-hydration ultrasonic method and detected its nanostructure, particle size, and zeta potential. Flow cytometry was used to detect the cell survival rate of each group after 24 h of drug treatment on inflammed Statens Seruminstitut Rabbit Corneal (SIRC) cells. Observed and recorded corneal epithelial staining, tear film rupture time, and Schirmer test to detect tear secretion on the ocular surface of rabbits. The corneal epithelial thickness, morphology, and number of bulbar conjunctival goblet cells were recorded by H&E staining. Finally, we detected the expression of VEGF, IL-1β, PGE2, and TNF-α by cellular immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Results: The encapsulation efficiency and drug loading of Tet-ATS@PLGA were 79.85% and 32.47%, respectively. At eye surface temperature, Tet can easily release from Tet-ATS@PLGA while that it was difficult to release at storage temperature and room temperature. After 2 weeks medication, Tet-ATS@PLGA can effectively improve the tear film rupture time and tear secretion time in a DED model (p <0.05). Compared with the normal group (62.34 ± 4.86 mm), the thickness of corneal epithelium in ATS (29.47 ± 3.21 mm), Tet-ATS (46.23 ± 2.87 mm), and Tet-ATS@PLGA (55.76 ± 3.95 mm) gradually increased. Furthermore, the flow cytometry indicated that Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory SIRC cells, and the cellular immunofluorescence and ELISA experiments showed that the expression intensity of inflammatory factors such as VEGF, IL-1β, PGE2, and TNF-α decreased in this process. Interestingly, Tet also had the effect of reducing intraocular pressure. Conclusion: Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory corneal epithelial cells, thus inhibiting the expression of inflammatory factors to block the formation of DED and improve the secretion of tear on the ocular surface.

PH/hyaluronidase dual responsive nano drug delivery systems for photothermal/chemotherapy combined treatment for non-small cell lung cancer

A biocompatible multifunctional nanocrystalline drug carrier system (RCDs-HA@AZD) with dual stimulation of pH and hyaluronidase has been developed for chemotherapy/photothermal combination therapy of non-small cell lung cancer (NSCLC).

Advanced methods to enhance lung cancer immunotherapy through novel drug delivery systems: Lipids and Micelles

The past few decades have witnessed a significant amount of research on lung cancer therapy as one of the leading mortality cause globally. Conventional treatments have disadvantages such as limited water solubility, drug resistance, and the damaging of healthy cells, resulting in decreased efficacy. As this outlook reports, immunotherapy integrated with drug delivery systems has been applied to exploit the synergistic and targeted effects. On the other hand, nanomedicine for cancer therapy has boosted efficacy and mitigated the negative effects substantially. Despite the persistence of obstacles such as drug resistance and insufficiency of stability, clinical studies demonstrated notable improvements in the cytotoxic efficacy of medications and in lowering treatment-related adverse effects. Technical approaches incorporating nanoparticles and innovative delivery strategies to enhance the effectiveness of targeted immunotherapy have been established. In the present review, a summary of the most promising literature aimed to break new ground in the use of immunotherapy and lipid and micelle-based nano drug delivery systems for lung cancer therapy has been presented, along with describing their key benefits, drawbacks, and prospects. The future of lung cancer therapy based on immune modulation will probably be combined with improved drug delivery systems to generate treatment methods of high efficacy.

Testing method for pharmaceutical water quality of inorganic hybrid nano drugs

Testing method for pharmaceutical water quality of inorganic hybrid nano drugs

Macrophage Membrane Camouflaged Cubosome for Doxorubicin and siRNA Delivery

In this research, the cell membrane camouflaging strategy was leveraged for the surface modification of cubosomes (CBs) to develop a bio–mimic nano–drug delivery system (Nano–DDS).

Targeting Wnt-β-Catenin Signaling Pathway for Hepatocellular Carcinoma Nanomedicine.

Hepatocellular carcinoma (HCC) represents a high-fatality cancer with a 5-year survival of 22%. The Wnt/β-catenin signaling pathway presents as one of the most upregulated pathways in HCC. However, it has so far not been targetable in the clinical setting. Therefore, studying new targets of this signaling cascade from a therapeutic aspect could enable reversal, delay, or prevention of hepatocarcinogenesis. Although enormous advancement has been achieved in HCC research and its therapeutic management, since HCC often occurs in the context of other liver diseases such as cirrhosis leading to liver dysfunction and/or impaired drug metabolism, the current therapies face the challenge of safely and effectively delivering drugs to the HCC tumor site. In this review, we discuss how a targeted nano drug delivery system could help minimize the off-target toxicities of conventional HCC therapies as well as enhance treatment efficacy. We also put forward the current challenges in HCC nanomedicine along with some potential therapeutic targets from the Wnt/β-catenin signaling pathway that could be used for HCC therapy. Overall, this review will provide an insight to the current advances, limitations and how HCC nanomedicine could change the landscape of some of the undruggable targets in the Wnt/β-catenin pathway.

Formulation and Biological Evaluation of Quorum Sensing Inhibitor-Based Nanoemulsion against Resistant Pseudomonal Infections

Antimicrobial resistance has raised a serious concern due to the lack of therapeutics to control pathogenic infections. Pseudomonas aeruginosa is considered a multidrug-resistant pathogen and a leading cause of hospital-acquired infections. Anti-virulence approach mainly focuses on targeting bacterial virulence despite its growth and proves effective against such drug-resistant pathogens. In this study, we select a novel flavonoid compound, 7,8-dihydroxyflavone (DHF), which has been reported as a quorum sensing inhibitor (QSI) of P. aeruginosa, performed its in-silico studies to observe its binding affinity and potential interactions with the target protein (2UV0) and further developed it as a nano drug formulation (DHF-NF), and performed its in-vitro and in-vivo evaluation. The prepared DHF-NF was examined for its efficacy in the prevention of wound-associated surface infections of P. aeruginosa in rats. The DHF-NF was prepared by using homogenization and examined for several physical parameters. The prepared DHF-NF had a spherical shape and smooth topology. The microbiological assays demonstrated the inhibitory potential of DHF-NF in a dose-dependent manner. The histological analysis of Pseudomonas infected tissue of rat skin showed significant activity in animal group treated with DHF-NF as compared to control groups. The microbiological and in-vivo evaluation results revealed that the compound, DHF, showed strong inhibitory potential and suggest that the DHF-NF could be utilized as novel anti-QS and anti-biofilm therapeutics against Pseudomonal surface infections.

Different Aspects of Nano-material and Biodegradable Polymers for Cancer Diagnosis and Treatment: A Review

Cancer, one of the most prevalent causes of death and disease, has a convoluted pathophysiology. Chemotherapy, immunotherapy and radiation therapy are examples of traditional cancer treatments. However, lack of selectivity, restrictions such cytotoxicity, and Drug resistance is a significant barrier to successful cancer treatment. With the development of nanotechnology, the study of cancer treatment has undergone a revolution. For treatment of cancer Nanoparticles can be used because of their special advantages, less toxicity, more good stability, stronger permeability, and exact placement. There are several varieties of nanoparticles. The innovative nanoparticle based drug delivery system makes advantage of characteristics of the tumour and its surroundings. Nanoparticles overcomes the disadvantages of conventional treatment of cancer in addition to avoiding multiple drug resistance. As additional multidrug resistance mechanisms are found and examined, nanoparticle research is also being pursued actively. The therapy includes consequences of Nano formulation have provided fresh perspectives on cancer treatment. The biggest chunk of studies, however, is restricted to in vivo and in vitro experiments, and the number of authorized Nano drugs has not increased significantly over time. This study covers a wide range of nanoparticle kinds, targeting strategies, and authorized Nanotherapy includes use in the cancer treatment. We also provide a summary of the pros, disadvantages, and present state of clinical translation.

A copper nanocluster-based multifunctional nanoplatform for augmented chemo/chemodynamic/photodynamic combination therapy of breast cancer

With the development of nano drug delivery system, the treatment mode that can overcome the shortcomings of chemotherapy drugs and integrate combined therapy remains to be explored. Herein, a nano drug system was designed to achieve the combined effect of chemo/chemodynamic/photodynamic therapy on cancer. Specifically, copper clusters (CuNCs) were used as the carrier, hyaluronic acid (HA) and doxorubicin (DOX) were coupled on CuNCs and then and chlorin e6 (Ce6) was introduced to form the self-assembled HA-CuNCs@DC nanoparticles. In this system, the HA-CuNCs@DC was involved in the reaction to the acidic tumor microenvironment (TME)-release of DOX, which could not only inhibit tumor growth through chemotherapy, but enhance the generation of hydrogen peroxide. CuNCs carriers had the properties of Fenton-like activity to realize chemodynamic therapy (CDT) and oxidase-like activity to deplete intracellular glutathione (GSH). Additionally, the chemotherapy drug susceptibility increased owing to the GSH depletion and the outbreak of reactive oxygen species, indicating the enhanced CDT efficacy and amplified chemotherapy efficacy. It was also noteworthy that Ce6 could be activated by 660 nm light to produce abundant singlet oxygen for photodynamic therapy. Overall, our platform demonstrated excellent biosafety and tumor suppression capabilities. This multimodal theranostic strategy provided new insights into cancer therapy.

Effect of Lipophilic Chains on the Antitumor Effect of a Dendritic Nano Drug Delivery System.

Oligoethylene glycol dendron (G2) has been used in drug delivery due to its unique dendritic structure and excellent properties. In order to investigate the effects of lipophilic chains on drug delivery, the amphiphilic hybrid compound G2-C18 is synthesized, and celastrol (CSL) is selected to prepare "core-shell" structured CSL-G2-C18 nanoparticles (NPs) via the antisolvent precipitation method. Meanwhile, CSL-G2 NPs are prepared as the control. The two NPs show similar particle sizes and polydispersity indexes, while their morphologies exhibit dramatic differences. CSL-G2 NPs are solid spherical particles, while G2-C18 NPs are vesicles. The two NPs present ideal stability and similar release tendencies. The in vitro toxicity results show that the cell inhibition effect of CSL-loaded NPs is significantly enhanced when compared with free CSL, and the antitumor effect of CSL-G2-C18 NPs is stronger than that of CSL-G2 NPs. The IC50 value of CSL-G2 NPs and CSL-G2-C18 NPs is enhanced about 2.8-fold and 5-fold when compared with free CSL, respectively. The above results show that lipophilic chain-linking dendritic hybrid nanocarriers promote antitumor activity by affecting the morphology of NPs, which may aid in the selection of carrier designs.

Anti-Cancer Effects of Trigonella foenum in Neuroblastoma Cell Line

Objective: Current approaches focus on the use of natural compounds in plants in the treatment of cancer. Trigonella foenum (Fenugreek) is mainly used in medicine, food, and cosmetics due to its bioactive and aromatic compounds. Many compounds with medicinal effects are found in Fenugreek seeds. These compounds have been demonstrated to be effective on numerous cancer cells. Neuroblastoma is one of the most common extracranial solid malignancies in children. In our study, the effects of Fenugreek on cell cytotoxicity, cell damage, migration, and sphere formation in neuroblastoma cells were investigated. Materials and Methods: The powder extract was dissolved in DMEM and filtered to prepare a stock solution of Fenugreek. We used MTT assay for the detection of cytotoxic effects of Fenugreek on SH-SY5Y cells, crystal violet staining for the analysis of morphological change in cells, wound healing test for the cell migration analysis, and agarose gel electrophoresis for detecting DNA damage. We created a spheroid to test the effect we observed in 2D culture, in 3D culture as well. Results: The findings of our study showed that Fenugreek treatments caused significant reductions in cell proliferation and migration capacities in 2D neuroblastoma cells at IC50 (1500 μg/ml) doses, respectively. In addition Fenugreek changed cell morphology and increased DNA fragmentation. Furthermore, Fenugreek caused disruption of 3D spheroid formation of SHSY-5Y cells in a dose- and time-dependent manner. Conclusion: The determination of the anti-cancer effect of Fenugreek on neuroblastoma cancer may be a useful and feasible intervention in neuroblastoma patients in the light of further studies and with the help of new nano drug delivery systems.

Preparation of Berberine@carbon Dots Nano-Formulation: Synthesis, Characterization and Herbicidal Activity against Echinochloa crus-galli and Amaranthus retroflexus Two Common Species of Weed.

Berberine (Ber) is easy to synthesize and has a variety of biological and pharmacological activities. At present, the existing studies on berberine have focused predominantly on its antibacterial activity; its herbicidal activity is rarely reported. In addition, there are a number of preparations of berberine, which are not enough to solve its shortcomings of low solubility and biological activity and the difficult storage of berberine. Here, berberine was combined with carbon dots to obtain carbon dots-berberine (CDs-Ber) nano formulation. The fluorescence quenching results showed that the CDs-Ber nano drug delivery system was successfully constructed, and the fluorescence quenching mechanism of the two was static quenching. The bioassay results showed that CDs had no adverse effects on the growth of barnyard grass (Echinochloa crus-galli) and redroot pigweed (Amaranthus retroflexus), and had high biocompatibility. Berberine and CDs-Ber predominantly affected the root growth of barnyard grass and redroot pigweed and could enhance the growth inhibition effect on weeds, to some extent. The results of the protective enzyme system showed that both berberine and CDs-Ber could increase the activities of Superoxide dismutase (SOD), Peroxidase (POD), and Catalase (CAT) in barnyard grass, and CDs-Ber had a stronger stress effect on barnyard grass than berberine. The determination of the number of bacterial communities in the soil after the berberine and CDs-Ber treatments showed that there was no significant difference in the effects of the two, indicating that CDs-Ber would not have more negative impacts on the environment. The CDs-Ber nano formulation improved the biological activity of berberine, enhanced the herbicidal effect, and was relatively safe for soil colonies.

Use of the quantum dot-labeled solid lipid nanoparticles for delivery of streptomycin and hydroxychloroquine: A new therapeutic approach for treatment of intracellular Brucella abortus infection

Brucellosis is considered one of the most important infectious diseases affecting any tissue and organ in the human body. Due to the intracellular pathogenesis of Brucella species, the use of conventional antibiotics for managing chronic brucellosis has several limitations. Therefore, the study focused on the use of solid lipid nanoparticles (SLN) to deliver streptomycin (STR) for intracellular infection, with or without the combination of hydroxychloroquine (HCQ) to evaluate if there might be a boost in the antibiotic effect when using the STR or STR-NPs alone. We used the double emulsion technique to synthesize Nano drug carriers; afterward, the physicochemical characteristics of synthesized Nano drug carriers were determined. The in vitro antibacterial activity of free drugs and Nano drug carriers were evaluated using well diffusion, broth microdilution assays (BMD), and murine macrophage-like cells cell line J774A.1. Additionally, acute and chronic phases of brucellosis were inducted into Wistar rats, and healing capacity of Nano drug carriers on liver and spleen tissues was compared with free drugs. The zeta potential of nanoparticles, means of size, Polydispersity Index (PDI), drugs loading, and encapsulation efficiency were 15.2 mV, 312.5 ± 26 nm, 0.433 ± 0.09, 16.6% and 89.5%, respectively. Well diffusion and BMD methods did not show a significantly differ between free drugs and nano drug carriers. However, the Nano drug carriers remarkably decreased the number of bacteria in the cell line compared to the free drugs. STR/HCQ-SLN enhanced the healing processes of the liver and spleen after brucellosis induction. STR/HCQ-SLN showed better inhibitory effects against the chronic phase of B. abortus infection in comparison to the STR-SLN, but this difference was not statistically significant. Using nanoplatforms to enhance conventional anti-brucellosis agents is promising, green and safe. Due to the continuous release of drugs, drugs increase their accumulation at the site of infection, causing a more significant effect on the chronic and acute phases of brucellosis.