Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis.

Tumour metastasis is a major cause of cancer treatment failure and death, and chemotherapy efficiency for gastric cancer patients is usually unsatisfactory due to tumour cell metastasis, poor targeting and serious adverse reactions. In this study, a kind of R8GD-modified epirubicin plus tetrandrine liposomes was prepared to enhance the antitumor efficiency via killing tumour cells, destroying tumour metastasis and inhibiting energy supply for tumour cells. In order to investigate the antitumour efficiency of the targeting liposomes, morphology observation, intracellular uptake, cytotoxic effects, and inhibition on tumour metastasis and energy supply were carried out in vitro, and tumour-bearing mice models were established to investigate the antitumour efficiency in vivo. In vitro results showed that R8GD-modified epirubicin plus tetrandrine liposomes with ideal physicochemical properties could kill the most tumour cells, inhibit tumour metastasis and cut-off energy supply for tumour cells. In vivo results exhibited that R8GD-modified epirubicin plus tetrandrine liposomes could enhance the accumulation in tumour site and display an obvious antitumor efficiency. Therefore, R8GD-modified epirubicin plus tetrandrine liposomes could be used as a potential therapy for treatment of gastric cancer.

Enhanced antitumour efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition.

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.

Functional vinorelbine plus schisandrin B liposomes destroying tumor metastasis in treatment of gastric cancer.

Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R8 (RRRRRRRR) modified vinorelbine plus schisandrin B liposomes had been successfully constructed for treating gastric cancer. In the liposomes, R8 was used to enhance the intracellular uptake, schisandrin B was incorporated into liposomes for inhibiting tumor cells metastasis, and vinorelbine was encapsulated into liposomes as antitumor drugs. Studies were performed on BGC-823 cells in vitro and were verified in the BGC-823 cell xenografts nude mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce BGC-823 cells apoptosis, 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 VEGF, VE-Cad, HIF-1a, PI3K, MMP-2, and FAK to inhibit tumor metastasis. In vivo results exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and induce tumor cell apoptosis. Hence, R8 modified vinorelbine plus schisandrin B liposomes might provide a safe and efficient therapy strategy for gastric cancer.

RPV-modified epirubicin and dioscin co-delivery liposomes suppress non-small cell lung cancer growth by limiting nutrition supply.

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.

Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis.

As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.

GGP modified daunorubicin plus dioscin liposomes inhibit breast cancer by suppressing epithelial-mesenchymal transition.

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.

Dual variable of drug loaded micelles in both particle and electrical charge on gastric cancer treatment.

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.

Combination of targeted daunorubicin liposomes and targeted emodin liposomes for treatment of invasive breast cancer.

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.

Development of R8 modified epirubicin-dihydroartemisinin liposomes for treatment of non-small-cell lung cancer.

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.