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1.
ACS Chem Neurosci ; 15(3): 593-607, 2024 02 07.
Article in English | MEDLINE | ID: mdl-38214579

ABSTRACT

Objective: Schisandrin B (Sch B) is a bioactive dibenzocyclooctadiene derizative that is prevalent in the fruit of Schisandra chinensis. Numerous studies have demonstrated that Sch B has a neuroprotective action by reducing oxidative stress and effectively preventing inflammation. It follows that Sch B is a potential treatment for Alzheimer's disease (AD). However, the drug's solubility, bioavailability, and lower permeability of the blood-brain barrier (BBB) can all reduce its efficacy during the therapy process. Therefore, this study constructed borneol-modified schisandrin B micelles (Bor-Sch B-Ms), which increase brain targeting by accurately delivering medications to the brain, effectively improving bioavailability. High therapeutic efficacy has been achieved at the pathological site. Methods: Bor-Sch B-Ms were prepared using the thin film dispersion approach in this article. On the one hand, to observe the targeting effect of borneol, we constructed a blood-brain barrier (BBB) model in vitro and studied the ability of micelles to cross the BBB. On the other hand, the distribution of micelle drugs and their related pharmacological effects on neuroinflammation, oxidative stress, and neuronal damage were studied through in vivo administration in mice. Results: In vitro studies have demonstrated that the drug uptake of bEnd.3 cells was increased by the borneol alteration on the surface of the nano micelles, implying that Bor-Sch B-Ms can promote the therapeutic effect of N2a cells. This could result in more medicines entering the BBB. In addition, in vivo studies revealed that the distribution and circulation time of medications in the brain tissue were significantly higher than those in other groups, making it more suitable for the treatment of central nervous system diseases. Conclusion: As a novel nanodrug delivery system, borneol modified schisandrin B micelles have promising research prospects in the treatment of Alzheimer's disease.


Subject(s)
Alzheimer Disease , Blood-Brain Barrier , Camphanes , Lignans , Polycyclic Compounds , Mice , Animals , Micelles , Alzheimer Disease/drug therapy , Endothelial Cells , Cyclooctanes
2.
Life Sci ; 285: 120013, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34614418

ABSTRACT

AIMS: Due to poor targeting ability of anti-tumor drugs and self-adaptation of tumors, the chemotherapy of ovarian cancer is still poorly effective. In recent years, the treatment of tumor with nano-targeted agents has become a potential research focus. In this study, a new type of short cell-penetrating peptide RPV-modified paclitaxel plus schisandrin B liposomes were constructed to disrupt VM channels, angiogenesis, proliferation and migration for the treatment of ovarian cancer. MATERIALS AND METHODS: In this study, clone assay, TUNEL, Transwell, wound-healing, CAM and mimics assay were used to detect the effects of RPV-modified liposomes on ovarian cancer SK-OV-3 cells before and after treatment. HE-staining, immunofluorescence and ELISA were used to further detect the expression of tumor-related proteins. KEY FINDINGS: RPV-modified paclitaxel plus schisandrin B liposomes can inhibit angiogenesis, VM channel formation, invasion and proliferation of ovarian SK-OV-3 cells. In vitro and in vivo studies showed that tumor-related protein expression was down-regulated. Modification of RPV can prolong the retention time of liposome in vivo and accumulate in the tumor site, increasing the anti-tumor efficacy. SIGNIFICANCE: The RPV-modified paclitaxel plus schisandrin B liposomes have good anti-tumor effect, thus may provide a new avenue for the treatment of ovarian cancer.


Subject(s)
Antineoplastic Agents/administration & dosage , Cell-Penetrating Peptides , Lignans/administration & dosage , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Polycyclic Compounds/administration & dosage , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cyclooctanes/administration & dosage , Cyclooctanes/chemistry , Female , Humans , Lignans/chemistry , Liposomes , Mice , Mice, Inbred BALB C , Paclitaxel/chemistry , Polycyclic Compounds/chemistry , Xenograft Model Antitumor Assays
3.
J Liposome Res ; 31(2): 113-129, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32200703

ABSTRACT

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Cell Line, Tumor , Cyclooctanes , Doxorubicin/pharmacology , Epithelial-Mesenchymal Transition , Humans , Lignans , Liposomes , Lung Neoplasms/drug therapy , Polycyclic Compounds , Vascular Endothelial Growth Factor A
4.
J Liposome Res ; 31(3): 267-278, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32757676

ABSTRACT

Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer's disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.


Subject(s)
Alzheimer Disease , Alzheimer Disease/drug therapy , Animals , Brain , Coumarins , Liposomes , Mice
5.
Int J Nanomedicine ; 15: 6451-6468, 2020.
Article in English | MEDLINE | ID: mdl-32922011

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. PURPOSE: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. METHODS AND RESULTS: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. CONCLUSION: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Tumor Microenvironment , A549 Cells , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Death/drug effects , Cell Movement/drug effects , Chickens , Endocytosis/drug effects , Epithelial-Mesenchymal Transition/drug effects , Humans , Hydrolysis , Liposomes , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Tumor Microenvironment/drug effects , Vinorelbine/pharmacology , Vinorelbine/therapeutic use
6.
J Drug Target ; 28(10): 1071-1084, 2020 12.
Article in English | MEDLINE | ID: mdl-32484364

ABSTRACT

Gastric cancer is a malignant tumour characterised by the uncontrolled cell growth. The incidence and mortality of gastric cancer remain high for the invasion and metastasis. We are urgently seeking a risk-free and effective treatment strategy for gastric cancer. In this study, paclitaxel and tetrandrine were encapsulated in the inner core of micelles, and DSPE-PEG2000-CPP and HA were modified on the micellar surface. HA/CPP modified paclitaxel plus tetrandrine micelles had a suitable particle size (90 nm) for permeating tumour tissue. The zeta potential of the targeting micelles was 8.37 mV after hydrolysis by HAase solution. Results of in vitro experiments indicated that HA/CPP modified paclitaxel plus tetrandrine micelles + HAase could enhance the intracellular uptake, inhibit the formation of neovascularization, block the process of EMT and destroy the invasion and metastasis. In vivo assays indicated that HA/CPP modified paclitaxel plus tetrandrine micelles could be selectively accumulated into tumour sites and exhibited the strong antitumor activity with negligible toxicity. These results suggested that HA/CPP modified paclitaxel plus tetrandrine micelles might provide a new strategy for treating gastric cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzylisoquinolines/pharmacology , Micelles , Paclitaxel/pharmacology , Stomach Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Benzylisoquinolines/administration & dosage , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Combinations , Drug Liberation , Humans , Mice , Mice, Inbred BALB C , Paclitaxel/administration & dosage , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Surface Properties
7.
Drug Dev Ind Pharm ; 46(6): 916-930, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32362146

ABSTRACT

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.


Subject(s)
Breast Neoplasms , Daunorubicin/chemistry , Diosgenin/analogs & derivatives , Epithelial-Mesenchymal Transition , Breast Neoplasms/drug therapy , Cell Line, Tumor , Diosgenin/chemistry , Humans , Liposomes
8.
Int J Nanomedicine ; 15: 2841-2858, 2020.
Article in English | MEDLINE | ID: mdl-32425521

ABSTRACT

INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aß oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. METHODS: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. RESULTS: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer's disease-related pathology. CONCLUSION: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.


Subject(s)
Alzheimer Disease/drug therapy , Blood-Brain Barrier/drug effects , Coumarins/pharmacology , Liposomes/pharmacology , Neuroprotective Agents/pharmacology , Alzheimer Disease/pathology , Animals , Blood-Brain Barrier/metabolism , Brain/drug effects , Brain/pathology , Cell Line , Coumarins/chemistry , Coumarins/pharmacokinetics , Humans , Liposomes/chemistry , Liposomes/pharmacokinetics , Mice, Transgenic , Neurons/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacokinetics , Polyethylene Glycols/chemistry , Presenilin-1/genetics , Rats, Sprague-Dawley , Tissue Distribution , Transferrin/chemistry
9.
J Drug Target ; 28(3): 245-258, 2020 03.
Article in English | MEDLINE | ID: mdl-31462111

ABSTRACT

Conventional treatment fails to completely eliminate highly invasive breast cancer cells, and most surviving breast cancer cells tend to reproliferate and metastasize by forming vasculogenic mimicry (VM) channels. Thus, a type of targeted liposomes was developed by modification with arginine8-glycine-aspartic acid (R8GD) to encapsulate daunorubicin and emodin separately. A combination of the two targeted liposomes was then developed to destroy VM channels and inhibit tumour metastasis. MDA-MB-435S cells, a highly invasive breast cancer, were then evaluated in vitro and in mice. The experiments indicated that R8GD modified daunorubicin liposomes plus R8GD modified emodin liposomes had small particle size, uniform particle size distribution and high drug encapsulation rate. The combination of the two targeted liposomes exerted strong toxicity on the MDA-MB-435S cells and effectively inhibited the formation of VM channels and the metastasis of tumour cells. Action mechanism studies showed that the R8GD modified daunorubicin liposomes plus R8GD modified emodin liposomes could downregulate some metastasis-related proteins, including MMP-2, VE-cad, TGF-ß1 and HIF-1α. These studies also demonstrated that the targeted liposomes allowed the chemotherapeutic drug to selectively accumulate at tumour site, thus exhibiting a distinct antitumor effect. Therefore, the combination of targeted daunorubicin liposomes and targeted emodin liposomes can provide a potential treatment for invasive breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Drug Delivery Systems , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/pathology , Daunorubicin/administration & dosage , Emodin/administration & dosage , Female , Humans , Liposomes , Mice , Neoplasm Invasiveness , Particle Size
10.
Cancer Sci ; 111(2): 621-636, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31777993

ABSTRACT

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Cell-Penetrating Peptides/chemistry , Diosgenin/analogs & derivatives , Epirubicin/administration & dosage , Lung Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , A549 Cells , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Diosgenin/administration & dosage , Diosgenin/chemistry , Diosgenin/pharmacology , Epirubicin/chemistry , Epirubicin/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Liposomes , Lung Neoplasms/pathology , Male , Mice , Rats , Xenograft Model Antitumor Assays
11.
Artif Cells Nanomed Biotechnol ; 47(1): 1947-1960, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31079495

ABSTRACT

Presently, there are no few anticancer drugs that have been used clinically due to their poor targeting ability, short half-life period, non-selective distributions, generation of vasculogenic mimicry (VM) channels, high metastasis, and high recurrence rate. This study aimed to explore the effects of R8 modified epirubicin-dihydroartemisinin liposomes that could target non-small-cell lung cancer (NSCLC) cells, destroy VM channels, inhibit tumor metastasis, and explain the possible underlying mechanism. In vitro assays indicated that R8 modified epirubicin-dihydroartemisinin liposomes with ideal physicochemical characteristics could exhibit not only powerful cytotoxicity on A549 cells, but also the effective suppression of VM channels and tumor metastasis. Mechanistic studies manifested that R8 modified epirubicin-dihydroartemisinin liposomes could down-regulate the levels of VE-Cad, TGF-ß1, MMP-2, and HIF-1α. In vivo assays indicated that R8 modified epirubicin-dihydroartemisinin liposomes could both increase the selective accumulation of chemotherapeutic drugs at tumor sites and show a targeting conspicuous of antitumor efficacy. In conclusion, the R8 modified epirubicin-dihydroartemisinin liposomes prepared in this study provide a treatment strategy with high efficiency for NSCLC.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Artemisinins/chemistry , Carcinoma, Non-Small-Cell Lung/pathology , Epirubicin/chemistry , Epirubicin/pharmacology , Lung Neoplasms/pathology , A549 Cells , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Biological Transport , Cell Adhesion/drug effects , Drug Liberation , Epirubicin/administration & dosage , Epirubicin/metabolism , Humans , Lipid Bilayers/metabolism , Liposomes , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Polyethylene Glycols/chemistry , Xenograft Model Antitumor Assays
12.
Artif Cells Nanomed Biotechnol ; 46(sup3): S524-S537, 2018.
Article in English | MEDLINE | ID: mdl-30299160

ABSTRACT

Glioma is the most common primary malignant brain tumor with a poor prognosis. The application of chemotherapeutic drugs is limited due to the existence of blood-brain barrier and serious side effects. Liposomes have been proven to be a stable and useful drug delivery system for tumors. In this paper, WGA (wheat germ agglutinin) modified vinorelbine cationic liposomes had been successfully constructed for treating glioma. In the liposomes, WGA was modified on the liposomal surface for crossing the blood-brain barrier and increasing the targeting effects, 3-(N-(N', N'-dimethylaminoethane) carbamoyl) cholesterol (DC-Chol) was used as cationic material and vinorelbine was encapsulated in the aqueous core of liposomes to inhibit tumor metastasis and kill tumor cells. Studies were performed on C6 cells in vitro and were verified in brain glioma-bearing mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce C6 cells apoptosis, promote drugs across the blood-brain barrier, inhibit the metastasis of tumor cells and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate PI3K, MMP-2, MMP-9 and FAK to inhibit tumor metastasis. Results in vivo exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and exhibited low toxicity to blood system and major organs. Hence, WGA modified vinorelbine cationic liposomes might provide a safe and efficient therapy strategy for glioma.


Subject(s)
Antineoplastic Agents, Phytogenic , Brain Neoplasms , Glioma , Vinorelbine , Wheat Germ Agglutinins , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/pharmacology , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glioma/drug therapy , Glioma/metabolism , Glioma/pathology , Liposomes , Mice , Neoplasm Metastasis , Neoplasm Proteins/biosynthesis , Vinorelbine/chemistry , Vinorelbine/pharmacokinetics , Vinorelbine/pharmacology , Wheat Germ Agglutinins/chemistry , Wheat Germ Agglutinins/pharmacokinetics , Wheat Germ Agglutinins/pharmacology
13.
Artif Cells Nanomed Biotechnol ; 46(sup2): 1154-1169, 2018.
Article in English | MEDLINE | ID: mdl-30043652

ABSTRACT

Treatment effect of chemotherapy for aggressive non-small-cell lung cancer (NSCLC) is usually unsatisfactory for non-selective distributions of anticancer drugs, generation of vasculogenic mimicry (VM) channels, high metastasis and recurrence rate. Therefore, we developed a kind of dequalinium (DQA) modified paclitaxel plus honokiol micelles in this study to destroy VM channels and inhibit tumour metastasis. In vitro assays indicated that the targeting paclitaxel micelles with ideal physicochemical characteristics could exhibit not only the powerful cytotoxicity on Lewis lung tumour (LLT) cells but also the effective suppression on VM channels and tumour metastasis. Action mechanism studies manifested that DQA modified paclitaxel plus honokiol micelles could activate apoptotic enzymes caspase-3 and caspase-9 as well as down-regulate FAK, PI3K, MMP-2 and MMP-9. In vivo assays indicated that polymeric micelles could increase selective accumulation of chemotherapeutic drugs at tumour sites and showed a conspicuous antitumour efficacy. Hence, the DQA modified paclitaxel plus honokiol micelles prepared in this study provided a potential treatment strategy for NSCLC.


Subject(s)
Antineoplastic Agents/pharmacology , Biphenyl Compounds/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Lignans/pharmacology , Lung Neoplasms/pathology , Micelles , Paclitaxel/pharmacology , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Dequalinium/chemistry , Drug Interactions , Drug Liberation , Humans , Mice , Neoplasm Metastasis , Paclitaxel/chemistry , Temperature , Xenograft Model Antitumor Assays
14.
Artif Cells Nanomed Biotechnol ; 46(sup1): 1180-1190, 2018.
Article in English | MEDLINE | ID: mdl-29519164

ABSTRACT

The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm. The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brain glioma-bearing mice. The action mechanisms were associated with dual-modifications by the glucose-lipid derivative and the dequalinium-lipid derivative, both of which are beneficial for the transport across the BBB. Furthermore, the modification with dequalinium-lipid derivative was able to target to the brain glioma cells and to the mitochondria. In conclusion, the functional docetaxel nanomicelles would be a promising formulation for the treatment of brain glioma, deserving further development for clinical trials.


Subject(s)
Brain Neoplasms/drug therapy , Docetaxel/chemistry , Docetaxel/pharmacology , Drug Compounding/methods , Glioma/drug therapy , Micelles , Nanostructures/chemistry , Animals , Apoptosis/drug effects , Biological Transport , Blood-Brain Barrier/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Transformation, Neoplastic , Docetaxel/metabolism , Docetaxel/therapeutic use , Glioma/pathology , Humans , Male , Mice , Mitochondria/metabolism
15.
J Nanosci Nanotechnol ; 18(8): 5320-5326, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-29458583

ABSTRACT

Diclofenac sodium (abrr. DS) and indomethacin (abrr. IMC) have been intercalated into the layered terbium hydroxide (LTbH) by anion exchange method. Chemical compositions, thermostability, morphology, luminescence property, release behaviors and cytotoxic effects have been investigated. The DS molecules may embed between layers with a bilayered arrangement and the IMC may correspond to a monolayered arrangement. The Tb3+ luminescence in DS-LTbH and IMC-LTbH composites were enhanced compared with LTbH precusor and the luminescence intensity increases with the deprotonation degree. Drug release was measured with HPLC, and LTbH showed sustained release behavior on both drugs. Further In Vitro evaluation were carried out on cancer cells. Cytotoxic effect of LTbH was observed with a sulforhodamine B colorimetric assay on a variety of cancer cell lines, which revealed that the LTbH showed little cytotoxic effect. Results indicate LTbH may offer a potential vehicle as an effective drug delivery system along with diagnostic integration.


Subject(s)
Drug Delivery Systems , Terbium/chemistry , Diclofenac , Drug Liberation , Hydroxides , Nanoparticles
16.
J Drug Target ; 26(9): 793-805, 2018 11.
Article in English | MEDLINE | ID: mdl-29334266

ABSTRACT

BACKGROUND: Breast cancer is an alarming global public health problem and a main cause of cancer-related death in women. Systemic chemotherapy is the most widely used treatment for breast cancer. However, current chemotherapy treatments are far from desirable due to poor targeting specificity, severe side effects and vasculogenic mimicry (VM). PURPOSE: Hyaluronic acid (HA)-modified daunorubicin plus honokiol (HNK) cationic liposomes were prepared and characterised for treatment of breast cancer by eliminating VM. METHODS: HA-modified daunorubicin plus HNK cationic liposomes were prepared by a thin-film hydration method. Evaluations were performed on MCF-7 cells and MDA-MB-435S cells, which are human breast cancer cells, and xenografts of MDA-MB-435S cells. RESULTS: In vitro results revealed that the HA-modified daunorubicin plus HNK cationic liposomes enhanced the cellular uptake and destroyed VM channels. In vivo results demonstrated that the liposomes prolonged the circulation time in the blood, obviously accumulated in the tumour region, and enhanced the overall anticancer effects. Action mechanisms were related to down-regulation of VM protein indicators including FAK, EphA2, MMP-2 and MMP-9. CONCLUSIONS: The prepared HA-modified daunorubicin plus HNK cationic liposomes may serve as a promising therapeutic strategy for the treatment of breast cancer.


Subject(s)
Biphenyl Compounds/chemistry , Breast Neoplasms/drug therapy , Daunorubicin/chemistry , Daunorubicin/therapeutic use , Hyaluronic Acid/chemistry , Lignans/chemistry , Liposomes , Animals , Breast Neoplasms/pathology , Cations , Female , Humans , MCF-7 Cells , Mice , Neovascularization, Pathologic
17.
Artif Cells Nanomed Biotechnol ; 46(sup1): 616-628, 2018.
Article in English | MEDLINE | ID: mdl-29381101

ABSTRACT

Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin. The action mechanism might be related to regulations on E-cadherin, α5ß1-integrin, TGF-ß1, VEGF and MMP2/9 in breast cancer cells. In vivo, the liposomes displayed a prolonged circulating time, more accumulation in tumor location, and a robust overall antitumor efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice. In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.


Subject(s)
Artemisinins/chemistry , Artemisinins/pharmacology , Breast Neoplasms/pathology , Daunorubicin/chemistry , Daunorubicin/pharmacology , Liposomes/chemistry , Octreotide/chemistry , Ammonium Sulfate/chemistry , Animals , Artemisinins/metabolism , Biological Transport , Cell Movement/drug effects , Daunorubicin/metabolism , Humans , Lipid Bilayers/chemistry , MCF-7 Cells , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Polyethylene Glycols/chemistry , Wound Healing/drug effects , Xenograft Model Antitumor Assays
18.
J Liposome Res ; 28(3): 236-248, 2018 Sep.
Article in English | MEDLINE | ID: mdl-28480778

ABSTRACT

CONTEXT: Non-small cell lung carcinoma (NSCLC) is a type of epithelial lung cancer that accounts for approximately 80-85% of lung carcinoma cases. Chemotherapy for the NSCLC is unsatisfactory due to multidrug resistance, nonselectively distributions and the accompanying side effects. OBJECTIVE: The objective of this study was to develop a kind of PTD modified paclitaxel anti-resistant liposomes to overcome these chemotherapy limitations. METHOD: The studies were performed on LLT cells and resistant LLT cells in vitro and on NSCLC xenograft mice in vivo, respectively. RESULTS AND DISCUSSION: In vitro results showed that the liposomes with suitable physicochemical characteristics could significantly increase intracellular uptake in both LLT cells and resistant LLT cells, evidently inhibit the growth of cancer cells, and clearly induce the apoptosis of resistant LLT cells. Studies on resistant LLT cells xenograft mice demonstrated that the liposomes magnificently enhanced the anticancer efficacy in vivo. Involved action mechanisms were down-regulation of adenosine triphosphate binding cassette transporters on resistant LLT cells, and activation of the apoptotic enzymes (caspase 8/9/3). CONCLUSION: The PTD modified paclitaxel anti-resistant liposomes may provide a promising strategy for treatment of the drug-resistant non-small cell lung cancer.


Subject(s)
Antineoplastic Agents/chemistry , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Resistance, Neoplasm/drug effects , Liposomes/chemistry , Lung Neoplasms/drug therapy , Paclitaxel/chemistry , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Drug Carriers , Drug Liberation , Humans , Male , Mice, Inbred C57BL , Oligopeptides/chemistry , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Particle Size , Surface Properties , Tamoxifen/chemistry , Tamoxifen/pharmacology , Xenograft Model Antitumor Assays
19.
Pharmacology ; 101(1-2): 43-53, 2018.
Article in English | MEDLINE | ID: mdl-28988243

ABSTRACT

BACKGROUND: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. METHODS: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. RESULTS: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. CONCLUSION: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dasatinib/administration & dosage , Mammary Neoplasms, Experimental/drug therapy , Vincristine/administration & dosage , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cell Cycle/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Dasatinib/therapeutic use , Female , Humans , Liposomes , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Mammary Neoplasms, Experimental/pathology , Mice, Inbred BALB C , Mice, Nude , Vincristine/therapeutic use
20.
Int J Nanomedicine ; 12: 7433-7451, 2017.
Article in English | MEDLINE | ID: mdl-29066893

ABSTRACT

Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Epirubicin/administration & dosage , Liposomes/administration & dosage , Lung Neoplasms/drug therapy , Animals , Antibiotics, Antineoplastic/chemistry , Antigens, CD/metabolism , Cadherins/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Caspase 3/metabolism , Cell Line, Tumor , Epirubicin/chemistry , Humans , Liposomes/chemistry , Liposomes/pharmacology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinases/metabolism , Xenograft Model Antitumor Assays
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