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1.
Biomed Pharmacother ; 168: 115687, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37837882

ABSTRACT

DNA methyltransferase inhibitors (DNMTis) have found widespread application in the management of cancer. Zebularine (Zeb), functioning as a demethylating agent, has exhibited notable advantages and enhanced therapeutic efficacy in the realm of tumour immunotherapy. Nevertheless, due to its lack of targeted functionality, standalone Zeb therapy necessitates the administration of a substantially higher dosage. In this investigation, we have devised an innovative nanodrug formulation, comprising the DNA methyltransferase inhibitor Zeb and pH-responsive chitosan (CS), hereinafter referred to as CS-Zeb nanoparticles (NPs). Our findings have unveiled that CS-Zeb NPs manifest heightened drug release within an acidic milieu (pH 5.5) in comparison to a neutral environment (pH 7.4). Furthermore, in vivo studies have conclusively affirmed that, in contrast to equivalent quantities of Zeb in isolation, the nanocomplex significantly curtailed tumour burden and protracted the survival duration of the B16F10 tumour-bearing murine model. Additionally, CS-Zeb NPs elicited an augmentation of CD8+ T cells within the peripheral circulation of mice and tumour-infiltrating lymphocytes (TILs). Notably, the dosage of CS-Zeb NPs was reduced by a remarkable 70-fold when juxtaposed with Zeb administered in isolation. To summarise, our study underscores the potential of CS-Zeb NPs as an alternative chemotherapeutic agent for cancer treatment.


Subject(s)
Chitosan , Nanoparticles , Neoplasms , Animals , Mice , Epigenesis, Genetic , Neoplasms/drug therapy , Neoplasms/genetics , Immunotherapy , DNA , Methyltransferases , Drug Carriers
2.
Asian J Pharm Sci ; 18(4): 100828, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37583709

ABSTRACT

Hepatocellular carcinoma (HCC) is now a common cause of cancer death, with no obvious change in patient survival over the past few years. Although the traditional therapeutic modalities for HCC patients mainly involved in surgery, chemotherapy, and radiotherapy, which have achieved admirable achievements, challenges are still existed, such as drug resistance and toxicity. The emerging gene therapy of clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9-based (CRISPR/Cas9), as an alternative to traditional treatment methods, has attracted considerable attention for eradicating resistant malignant tumors and regulating multiple crucial events of target gene-editing. Recently, advances in CRISPR/Cas9-based anti-drugs are presented at the intersection of science, such as chemistry, materials science, tumor biology, and genetics. In this review, the principle as well as statues of CRISPR/Cas9 technique were introduced first to show its feasibility. Additionally, the emphasis was placed on the applications of CRISPR/Cas9 technology in therapeutic HCC. Further, a broad overview of non-viral delivery systems for the CRISPR/Cas9-based anti-drugs in HCC treatment was summarized to delineate their design, action mechanisms, and anticancer applications. Finally, the limitations and prospects of current studies were also discussed, and we hope to provide comprehensively theoretical basis for the designing of anti-drugs.

3.
J Control Release ; 361: 727-749, 2023 09.
Article in English | MEDLINE | ID: mdl-37591461

ABSTRACT

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.


Subject(s)
CRISPR-Cas Systems , Neoplasms , Gene Editing , Technology , Neoplasms/genetics , Neoplasms/therapy
4.
J Colloid Interface Sci ; 650(Pt A): 526-540, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37423180

ABSTRACT

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+ were recovered in response to TME stimulation. The introduction of Cu2+ triggered the charge reversal of UCCu2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.


Subject(s)
Biological Products , Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Neoplasms , Humans , Copper/chemistry , Carcinoma, Hepatocellular/drug therapy , Hydrogen Peroxide , Liver Neoplasms/drug therapy , Nanoparticles/chemistry , Cell Line, Tumor , Neoplasms/drug therapy , Glutathione , Tumor Microenvironment
5.
Small ; 19(27): e2208228, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36974577

ABSTRACT

The rational structural design of the electrode materials is significant to enhance the electrochemical performance for potassium ion storage, benefiting from the shortened ion diffusion distance, increased conductivity, and pseudo-capacitance promotion. Herein, hydrated vanadium oxide (HVO) nanosheets with enriched oxygen defects are well confined into hollow mesoporous carbon spheres (HMCS), producing Od -VOH@C nanospheres through one-step hydrothermal reaction. Attributed to the restricted growth in the HMCS, the HVO nanosheets are loosely packed, generating abundant interfacial boundaries and large specific areas. As a result, Od -VOH@C nanospheres show increased reaction kinetics and well buffer the volume effects for the K+ storage. Od -VOH@C delivers stable capacities of 138 mAh g-1 at 2.0 A g-1 over 10 000 cycles in half-cells attributed to the high pseudo-capacitance contribution. The K+ storage mechanism of insertion and conversion reaction is confirmed by ex situ X-ray diffraction, Raman, and X-ray photoelectron spectroscopy analyses. Moreover, the symmetric potassium-ion capacitors of Od -VOH@C//Od -VOH@C deliver a high energy density of 139.6 Wh kg-1 at the power density of 948.3 W kg-1 .

6.
ACS Appl Mater Interfaces ; 15(12): 15893-15906, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-36940438

ABSTRACT

The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.


Subject(s)
Nanoparticles , Neoplasms , Tumor Hypoxia , Reactive Oxygen Species/chemistry , Nanoparticles/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Intracellular Space , Tumor Microenvironment , Drug Delivery Systems , Gemcitabine/chemistry , Gemcitabine/pharmacology , Combined Modality Therapy , Humans , Animals , Mice , HeLa Cells
7.
J Colloid Interface Sci ; 635: 441-455, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36599242

ABSTRACT

Therapeutic modalities and drug formulations play a crucial and prominent role in actualizing effective treatment and radical cures of tumors. However, the therapeutic efficiency was severely limited by tumor recurrence and complex multi-step preparation of formulation. Therefore, the exploration of novel nanoparticles via a simple and green synthesis process for conquering traditional obstacles and improving therapeutic efficiency is an appealing, yet remarkably challenging task. Herein, a universal nanoplatform allows all cancerous cell-targeting, acid-responsive, cell imaging, synergistic chemotherapy, and nucleolar targeted phototherapy function was tactfully designed and constructed by using chemotherapeutic agents ursolic acid (UA), sorafenib (SF), and carbon dots (CDs) photosensitizers (PSs). The designed US NPs were formed by self-assembly of UA and SF associated with electrostatic, π-π stacking, and hydrophobic interactions. After hydrogen bonding reaction with CDs, the obtained (denoted as USC NPs) have a relatively uniform size of an average 125.6 nm, which facilitated the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free CDs solution. Both in vitro and in vivo studies revealed that the advanced platform commenced synergistic anticancer therapeutic potency, imperceptible systematical toxicity, and remarkable reticence towards drug-resistant cancer cells. Moreover, the CDs PSs possess intrinsic nucleolus-targeting ability. Taken together, this theranostics system can fully play the role of "killing three birds with one stone" in a safe manner, implying a promising direction for exploring treatment strategies for cancer and endowing them with great potential for future translational research and providing a new vision for the advancing of an exceptionally forceful protocol for practical cancer therapy.


Subject(s)
Antineoplastic Agents , Nanoparticles , Neoplasms , Humans , Antineoplastic Agents/chemistry , Phototherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Nanoparticles/chemistry , Cell Line, Tumor
8.
Biomater Sci ; 10(21): 6267-6281, 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36128848

ABSTRACT

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.


Subject(s)
Dendrimers , Hyperthermia, Induced , Nanoparticles , Neoplasms , Humans , Indocyanine Green/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Epithelial Cell Adhesion Molecule , Doxorubicin/pharmacology , Delayed-Action Preparations , Precision Medicine , Disulfiram , Drug Delivery Systems/methods , Neoplasms/therapy , Lactic Acid , Hyperthermia, Induced/methods , Drug Liberation , Theranostic Nanomedicine/methods , Cell Line, Tumor
9.
ACS Appl Mater Interfaces ; 14(37): 42541-42557, 2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36094305

ABSTRACT

Nanotechnology has shown a revolution in cancer treatments, including breast cancers. However, there remain some challenges and translational hurdles. Surgery, radiotherapy, and chemotherapy are the primary treatment methods for breast cancer, although drug combinations showed promising results in preclinical studies. Herein we report the development of a smart drug delivery system (DDS) to efficiently treat breast cancer by pyroptosis-starvation-chemotherapeutic combination. Cancer-starvation agent glucose oxidase was chemically attached to synthesized iron oxide nanoparticles which were entrapped inside poly(lactic-co-glycolic acid) along with apoptosis-associated speck-like protein containing a caspase recruitment domain plasmid and paclitaxel (PTX). An emulsion solvent evaporation method was used to prepare the DDS. The surface of the DDS was modified with chitosan to which aptamer was attached to achieve site-specific targeting. Hence, the prepared DDS could be targeted to a tumor site by both external magnet and aptamer to obtain an enhanced accumulation of drugs at the tumor site. The final size of the aptamer-decorated DDS was less than 200 nm, and the encapsulation efficiency of PTX was 76.5 ± 2.5%. Drug release from the developed DDS was much higher at pH 5.5 than at pH 7.4, ensuring the pH sensitivity of the DDS. Due to efficient dual targeting of the DDS, in vitro viability of 4T1 cells was reduced to 12.1 ± 1.6%, whereas the nontargeted group and free PTX group could reduce the viability of cells to 29.2 ± 2.4 and 46.2 ± 1.6%, respectively. Our DDS showed a synergistic effect in vitro and no severe side effects in vivo. This DDS has strong potential to treat various cancers.


Subject(s)
Breast Neoplasms , Chitosan , Nanoparticles , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Chitosan/therapeutic use , Drug Delivery Systems/methods , Emulsions , Female , Glucose Oxidase/therapeutic use , Humans , Magnetic Phenomena , Nanoparticles/chemistry , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use , Polymers/chemistry , Pyroptosis , Solvents
10.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112177, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34749194

ABSTRACT

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Animals , Biomimetics , Cell Line, Tumor , HeLa Cells , Humans , Indocyanine Green , Mice , Photosensitizing Agents , Phototherapy , Photothermal Therapy , Polyphenols , TOR Serine-Threonine Kinases
11.
Int J Pharm ; 605: 120784, 2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34111544

ABSTRACT

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.


Subject(s)
Ginsenosides , Nanoparticles , Administration, Cutaneous , Drug Delivery Systems , Insulin , Permeability , Skin
12.
Acta Pharm Sin B ; 11(1): 246-257, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33532190

ABSTRACT

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment.

13.
ACS Appl Mater Interfaces ; 12(51): 57362-57372, 2020 Dec 23.
Article in English | MEDLINE | ID: mdl-33301289

ABSTRACT

The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene-chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core-shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene-drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site in vivo and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene-drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.


Subject(s)
CRISPR-Cas Systems , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Sorafenib/therapeutic use , Animals , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/toxicity , CRISPR-Associated Protein 9/genetics , Cell Line, Tumor , Drug Carriers/chemistry , Drug Carriers/toxicity , Drug Liberation , Epithelial Cell Adhesion Molecule/chemistry , ErbB Receptors/genetics , ErbB Receptors/metabolism , Gene Editing , Genes, erbB-1 , Humans , Mice , Nanoparticles/toxicity , Polyamines/chemistry , Polyamines/toxicity , Porosity , Signal Transduction/drug effects , Silicon Dioxide/toxicity
14.
Pharmacol Res ; 159: 105031, 2020 09.
Article in English | MEDLINE | ID: mdl-32562816

ABSTRACT

Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.


Subject(s)
Blood Platelets/drug effects , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Ginsenosides/therapeutic use , Muscle, Smooth, Vascular/drug effects , Neointima , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation/drug effects , Vascular Remodeling/drug effects , Animals , Biological Availability , Blood Platelets/metabolism , Cardiovascular Agents/adverse effects , Cardiovascular Agents/pharmacokinetics , Cardiovascular Diseases/blood , Cardiovascular Diseases/pathology , Ginsenosides/adverse effects , Ginsenosides/pharmacokinetics , Humans , Molecular Structure , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Signal Transduction , Structure-Activity Relationship
15.
Eur J Pharm Sci ; 142: 105100, 2020 Jan 15.
Article in English | MEDLINE | ID: mdl-31669385

ABSTRACT

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.


Subject(s)
Anticoagulants/pharmacology , Cardiovascular Diseases/drug therapy , Ginsenosides/pharmacology , Herb-Drug Interactions/physiology , Warfarin/pharmacology , Animals , Blood Coagulation/drug effects , Cardiovascular Diseases/metabolism , Cell Line , Cytochrome P-450 Enzyme System/metabolism , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Intercellular Adhesion Molecule-1/metabolism , Liver/drug effects , Liver/metabolism , Panax/chemistry , Plant Extracts/pharmacology , Rats , Thrombosis/drug therapy , Thrombosis/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
16.
Sensors (Basel) ; 19(20)2019 Oct 19.
Article in English | MEDLINE | ID: mdl-31635086

ABSTRACT

Sparse signal processing theory has been applied to synthetic aperture radar (SAR) imaging. In compressive sensing (CS), the sparsity is usually considered as a known parameter. However, it is unknown practically. For many functions of CS, we need to know this parameter. Therefore, the estimation of sparsity is crucial for sparse SAR imaging. The sparsity is determined by the size of regularization parameter. Several methods have been presented for automatically estimating the regularization parameter, and have been applied to sparse SAR imaging. However, these methods are deduced based on an observation matrix, which will entail huge computational and memory costs. In this paper, to enhance the computational efficiency, an efficient adaptive parameter estimation method for sparse SAR imaging is proposed. The complex image-based sparse SAR imaging method only considers the threshold operation of the complex image, which can reduce the computational costs significantly. By utilizing this feature, the parameter is pre-estimated based on a complex image. In order to estimate the sparsity accurately, adaptive parameter estimation is then processed in the raw data domain, combining with the pre-estimated parameter and azimuth-range decouple operators. The proposed method can reduce the computational complexity from a quadratic square order to a linear logarithm order, which can be used in the large-scale scene. Simulated and Gaofen-3 SAR data processing results demonstrate the validity of the proposed method.

17.
J Mater Chem B ; 7(44): 6914-6923, 2019 11 28.
Article in English | MEDLINE | ID: mdl-31482166

ABSTRACT

The combination of chemotherapy and photothermal therapy displays improved anti-cancer effects and lower systematic toxicity of a free drug compared with monotherapy. In this study, we designed innovative, carrier-free nanodrugs (PTX/ICG NDs) composed of the chemotherapeutic agent paclitaxel (PTX) and the photosensitizer indocyanine green (ICG) via self-assembly. The nanodrugs not only incorporated two different modalities into one delivery system for combined chemo-photothermal therapy but also enhanced the solubility of PTX without the need for any carrier. The as-prepared PTX/ICG NDs exhibited the merits of a relatively uniform size of 140 ± 1.4 nm, surface charge of -36 ± 2.2 mV, and high drug loading content of PTX. The combination strategy exerted a synergistic effect on the cytotoxicity of cancer cells in vitro, which could be attributed to the high cellular uptake and sustained release of PTX. Furthermore, an in vivo study indicated that PTX/ICG NDs showed higher accumulation in the tumor site than free ICG and possessed strong synergistic chemo-photothermal therapy efficacy against tumors in H22 tumor-bearing mice. Taken together, our study demonstrates that PTX/ICG NDs hold promise to become an alternative chemo-photothermal therapy agent to treat cancers.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drug Delivery Systems , Indocyanine Green/chemistry , Nanoparticles , Paclitaxel/pharmacology , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Cell Line, Tumor , Cell Survival , Coloring Agents/chemistry , Drug Design , Humans , Mice , Neoplasms, Experimental , Paclitaxel/chemistry , Rats
18.
Eur J Med Chem ; 179: 916-935, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31306818

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Traditional chemotherapy drugs are hard to reach a satisfactory therapeutic effect since advanced HCC is highly chemo-resistant. Sorafenib is an oral multikinase inhibitor that can suppress tumor cell proliferation, angiogenesis and induce cancer cell apoptosis. However, the poor solubility, rapid metabolism and low bioavailability of sorafenib greatly restricted its further clinical application. During the past decade, numerous sorafenib derivatives have been designed and synthesized to overcome its disadvantages and improve its clinical performance. This article focuses on the therapeutic effects and mechanisms of various sorafenib derivatives with modifications on the N-methylpicolinamide group, urea group, central aromatic ring or others. More importantly, this review summarizes the current status of the structure-activity relationship (SAR) of reported sorafenib derivatives, which can provide some detailed information of future directions for further structural modifications of sorafenib to discovery new anti-tumor drugs with improved clinical performance.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Sorafenib/pharmacology , Animals , Antineoplastic Agents/chemistry , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Proliferation/drug effects , Chemistry, Pharmaceutical , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Molecular Structure , Protein Kinase Inhibitors/chemistry , Sorafenib/chemistry
19.
Sensors (Basel) ; 19(3)2019 Jan 25.
Article in English | MEDLINE | ID: mdl-30691042

ABSTRACT

Wide angle synthetic aperture radar (WASAR) receives data from a large angle, which causes the problem of aspect dependent scattering. L 1 regularization is a common compressed sensing (CS) model. The L 1 regularization based WASAR imaging method divides the whole aperture into subapertures and reconstructs the subaperture images individually. However, the aspect dependent scattering recovery of it is not accurate. The subaperture images of WASAR can be regarded as the SAR video. The support set among the different frames of SAR video are highly overlapped. Least squares on compressed sensing residuals (LS-CS-Residuals) can reconstruct the time sequences of sparse signals which change slowly with time. This is to replace CS on the observation by CS on the least squares (LS) residual computed using the prior estimate of the support. In this paper, we introduce LS-CS-Residual into WASAR imaging. In the iteration of LS-CS-Residual, the azimuth-range decoupled operators are used to avoid the huge memory cost. Real data processing results show that LS-CS-Residual can estimate the aspect dependent scatterings of the targets more accurately than CS based methods.

20.
Sensors (Basel) ; 19(2)2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30650524

ABSTRACT

Sparse signal processing has already been introduced to synthetic aperture radar (SAR), which shows potential in improving imaging performance based on raw data or a complex image. In this paper, the relationship between a raw data-based sparse SAR imaging method (RD-SIM) and a complex image-based sparse SAR imaging method (CI-SIM) is compared and analyzed in detail, which is important to select appropriate algorithms in different cases. It is found that they are equivalent when the raw data is fully sampled. Both of them can effectively suppress noise and sidelobes, and hence improve the image performance compared with a matched filtering (MF) method. In addition, the target-to-background ratio (TBR) or azimuth ambiguity-to-signal ratio (AASR) performance indicators of RD-SIM are superior to those of CI-SIM in down-sampling data-based imaging, nonuniform displace phase center sampling, and sparse SAR imaging model-based azimuth ambiguity suppression.

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