Regulating Stem Cell-Related Genes Induces the Plastic Differentiation of Cancer Stem Cells to Treat Breast Cancer.

Relapse of cancer is associated with multidirectional differentiation and unrestricted proliferative replication potential of cancer stem cells. Herein, we propose the plastic differentiation strategy for irreversible differentiation of cancer stem cells; further, salinomycin and its newly constructed functional liposomes are used to implement this strategy. Whole gene, cancer stem cell-related RNA, and protein expression analyses reveal that salinomycin induces the cancer stem cells into normal cells, dormant cells, and mature cancer cells. Besides, the results indicate that the gatekeeper is related to the inhibition of the protein kinase C (PKC) α signaling pathway. The differentiated normal or dormant cells are incorporated into normal tissue, whereas the rest are killed by chemotherapy. The findings would offer the evidence for plastic differentiation of cancer stem cells and propose a novel strategy for cancer therapy.

A Precise Nanostructure of Folate-Overhung Mitoxantrone DNA Tetrahedron for Targeted Capture Leukemia.

Regular chemotherapy cannot eliminate leukemic cells, due to the sparse distribution of cancer cells in leukemia patients. Here, we report a precise nanostructure of folate-overhung mitoxantrone DNA tetrahedron that enables the treatment of leukemic cells by targeted action. Folate is used as a targeting molecule and synthesized with DNA strand in forming the folate-overhang DNA complement, and the complement is then separately base-paired onto six sides of the fabricated DNA tetrahedron. Mitoxantrone is used as an anticancer agent and intercalated into the double strands of the folate-overhung DNA tetrahedron for drug loading. The evaluation studies are performed on leukemia BALL-1 and K562 cells. The results demonstrate that the folate-overhung mitoxantrone DNA tetrahedra (approximately 25 nm) are able to target leukemic cells, transport across the nuclei membrane, induce the apoptosis, and enhance the overall efficacy of treating leukemic cells in vitro and in leukemia-bearing mice. This study provides a potential drug-containing DNA nanostructure, to clean the sparsely distributed leukemic cells in patients.

Nanostructured SL9-CpG Lipovaccines Elicit Immune Response for the Treatment of Melanoma.

Antigen peptides and adjuvants have been extensively investigated for cancer immunotherapy, and they are expected to elicit specific immune responses for cancer treatment. However, the anti-cancer efficacy of antigen peptide and adjuvant-based cancer vaccines has been limited due to the inefficient delivery to draining lymph nodes after administration. Therefore, it is necessary to develop a suitable delivery system to transport antigen peptides and adjuvants. Here, we report a novel type of nanostructured lipovaccines for the treatment of melanoma by delivering antigen peptide (SL9) and oligodeoxynucleotide adjuvant (CpG) to the lymphatic vessels and to the draining lymph node. The SL9-CpG lipovaccines were characterized using dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The lymph uptake, immune response elicitation and treatment effects were evaluated on melanoma-bearing C57BL/6 mice using flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA) and tumor inhibitory efficacy. The SL9-CpG lipovaccines were uniform with a nanoscale size (~70 nm), had high encapsulation efficiency, and exhibited effective lymph uptake, resulting in activation of specific cytotoxic CD8+ T cells, and release of IFN-γ, and a robust inhibition of tumor growth. Therefore, the nanostructured SL9-CpG lipovaccines offer a promising strategy for melanoma treatment.

Development of double strand RNA mPEI nanoparticles and application in treating invasive breast cancer.

Triple negative breast cancer (TNBC) has been characterized as a very heterogeneous subtype, and is more invasive and non-expressing of the genes for the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu, with poor prognosis, and hence the efficacy of regular chemotherapy is very limited. Here, we report a kind of double strand RNA (dsRNA) mPEI nanoparticle for treatment of invasive TNBC. The studies were performed on TNBC cells in vitro and in TNBC cancer-bearing mice. The results showed that dsRNA mPEI nanoparticles were able to effectively transfect cells, and demonstrated a strong capability in knocking-down the Fra-1 gene and down-stream MMP-1 and MMP-9 genes in TNBC cells and TNBC cancer-bearing mice, thereby inhibiting the invasion and migration of cells. After intratumoral injection, dsRNA mPEI nanoparticles exhibited a robust anticancer efficacy in TNBC cancer-bearing mice, and the anticancer efficacy was superior to that of paclitaxel. In conclusion, dsRNA mPEI nanoparticles are able to effectively treat aggressive TNBC, and the mechanism studies reveal that they take effect by knocking-down Fra-1 relevant genes, hence interfering in transcription and translation of the genes, which are necessary for growth and metastasis of TNBC. Therefore, the present study offers a new and promising formulation and strategy for effective treatment of TNBC.

Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy.

BACKGROUND: The existing chemo/radiotherapy fail to eliminate cancer cells due to the restriction of either drug resistance or radio tolerance. The predicament urges researchers to continuously explore alternative strategy for achieving a potent curative effect. METHODS: Functional chlorin gold nanorods (Ce6-AuNR@SiO2-d-CPP) were fabricated aiming at treating breast cancer by photothermal/photodynamic therapy (PTT/PDT). The nanostructure was developed by synthesizing Au nanorods as the photothermal conversion material, and by coating the pegylated mesoporous SiO2 as the shell for entrapping photosensitizer Ce6 and for linking the D-type cell penetrating peptide (d-CPP). The function of Ce6-AuNR@SiO2-d-CPP was verified on human breast cancer MCF-7 cells and MCF-7 cells xenografts in nude mice. RESULTS: Under combinational treatment of PTT and PDT, Ce6-AuNR@SiO2-d-CPP demonstrated a strong cytotoxicity and apoptosis inducing effects in breast cancer cells in vitro, and a robust treatment efficacy in breast cancer-bearing nude mice. The uptake mechanism involved the energy-consuming caveolin-mediated endocytosis, and Ce6-AuNR@SiO2-d-CPP in PTT/PDT mode could induce apoptosis by multiple pathways in breast cancer cells. CONCLUSION: Ce6-AuNR@SiO2-d-CPP demonstrated a robust efficacy in the treatment of breast cancer by photothermal/photodynamic therapy. Therefore, the present study could offer a new promising strategy to treat the refractory breast cancer.

Nanostructured Dihydroartemisinin Plus Epirubicin Liposomes Enhance Treatment Efficacy of Breast Cancer by Inducing Autophagy and Apoptosis.

The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.

Development of functional docetaxel nanomicelles for treatment of brain glioma.

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.

Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes.

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.

Lipid vesicles containing transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8 efficiently treat brain glioma along with glioma stem cells.

Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.

The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer.

Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer.

Dual-functional drug liposomes in treatment of resistant cancers.

Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug-containing phospholipid bilayer vesicles that possess a dual-function of providing the basic efficacy of drug and the extended effect of the drug carrier. They exhibit unique roles in treatment of resistant cancer via circumventing drug efflux caused by adenosine triphosphate binding cassette (ABC) transporters, eliminating cancer stem cells, destroying mitochondria, initiating apoptosis, regulating autophagy, destroying supply channels, utilizing microenvironment, and silencing genes of the resistant cancer. As the prospect of an estimation, dual-functional drug liposomes would exhibit more strength in their extended function, hence deserving further investigation for clinical validation.

C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma.

Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.

Destruction of vasculogenic mimicry channels by targeting epirubicin plus celecoxib liposomes in treatment of brain glioma.

The efficacy of chemotherapy for brain glioma is restricted by the blood-brain barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the treatment of intracranial glioma-bearing nude mice. Therefore, targeting epirubicin plus celecoxib liposomes could be a potential nanostructured formulation to treat gliomas and destroy their VM channels.

Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating Brain Glioma and Glioma Stem Cells.

The highly infiltrative nature of brain glioma makes total surgical removal of cancerous cells virtually impossible. Regular chemotherapy plays an important role in eradicating the residual cancer cells but is ineffective in treating brain glioma due to the hindrance of drug penetration into the tumor site by the blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem cells (GSCs). In this study, functional targeting daunorubicin liposomes were developed by modifying the liposomes with distearoylphosphatidylethanolamine polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the glioma stem cells. The results showed that the functional targeting daunorubicin liposomes were able to significantly transfer across the BBB and exhibited an obvious efficacy in killing glioma and glioma stem cells in mice. The action mechanisms of the functional targeting daunorubicin liposomes were related to their properties: long-duration circulation in the blood system, transport capability across the BBB, concentrated accumulation in the brain glioma site, and increased internalization by malignant cells and their mitochondria. This functional drug formulation showed anticancer efficacy through a direct cytotoxic effect and an apoptosis-inducing effect through the apoptotic signaling pathways in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for treating brain glioma, functional targeting daunorubicin liposomes have the potential to eliminate brain glioma along with glioma stem cells.

Application of functional vincristine plus dasatinib liposomes to deletion of vasculogenic mimicry channels in triple-negative breast cancer.

Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while the residual cancer cells readily form the vasculogenic mimicry (VM) channels, which lead to the relapse of cancer after treatment. In this study, the functional vincristine plus dasatinib liposomes, modified by a targeting molecule DSPE-PEG2000-c(RGDyK), were fabricated to address this issue. The investigations were performed on TNBC MDA-MB-231 cells and MDA-MB-231 xenografts in nude mice. The liposomes exhibited the superior performances in the following aspects: the enhancement of cellular uptake via targeted action; the induction of apoptosis via activation of caspase 8, 9, and 3, increased expression of Bax, decreased expression of Mcl-1, and generation of reactive oxygen species (ROS); and the deletion of VM channels via inhibitions on the VM channel indicators, which consisted of vascular endothelial-cadherin (VE-Cad), focal adhesion kinase (FAK), phosphatidylinositide 3-kinase (PI3K), and matrix metallopeptidases (MMP-2, and MMP-9). Furthermore, the liposomes displayed the prolonged circulation time in the blood, the increased accumulation in tumor tissue, and the improved therapeutic efficacy along with deletion of VM channels in the TNBC-bearing mice. In conclusion, the nanostructured functional drug-loaded liposomes may provide a promising strategy for the treatment of invasive TNBC along with deletion of VM channels.

A Combination of Targeted Sunitinib Liposomes and Targeted Vinorelbine Liposomes for Treating Invasive Breast Cancer.

Regular chemotherapy cannot eradicate invasive breast cancer cells and the residual cancer cells will form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for cancer masses prior to angiogenesis. This phenomenon is a major reason for the recurrence of invasive breast cancer after treatment. In this study, a novel type of targeted liposomes was developed by modifying a mitochondria-tropic material, D-a-tocopheryl polyethylene glycol 1000 succinate- triphenylphosphine conjugate (TPGS1000-TPP), to encapsulate sunitinib and vinorelbine separately and a combination of the two targeted drug liposomes was used to treat invasive breast cancer as well as VM channels. Evaluations were performed in breast cancer MCF-7 cells and highly invasive breast cancer MDA-MB-435S cells in vitro and in mice. The results determined that the functional material (TPGS1000-TPP) and suitable size of the liposomes (90-100 nm) resulted in prolonged blood circulation, an enhanced permeability retention (EPR) effect in cancer tissue, and a mitochondrial targeting effect. Targeted drug liposomes were internalized via cellular uptake and accumulated in the mitochondria of invasive breast cancer cells or VM channel-forming cancer cells to induce acute cytotoxic injury and apoptosis. Activated apoptotic enzymes caspase 9 and caspase 3 as well as down-regulated VM channel-forming indicators (MMP-9, EphA2, VE-Cadherin, FAK and HIF-1α) contributed to significantly enhanced efficacy. Therefore, a combination of targeted sunitinib liposomes and targeted vinorelbine liposomes may provide an effective strategy for treating invasive breast cancer and prevent relapse arising from VM channels.

A nanostructure of functional targeting epirubicin liposomes dually modified with aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma treatment.

The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin ß3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.

Targeting Epirubicin Plus Quinacrine Liposomes Modified with DSPE-PEG2000-C(RGDfK) Conjugate for Eliminating Invasive Breast Cancer.

Recurrence of invasive breast cancer could arise from the residual cancer cells after comprehensive treatment. It is possible that residual invasive cancer cells are capable of forming highly patterned vasculogenic mimicry (VM) channels, leading to relapse and metastasis. In the present study, a new type of targeting epirubicin plus quinacrine liposomes was developed by modifying functional DSPE-PEG2000 with C(RGDfK), a cyclic peptide containing Arg-Gly-Asp. These liposomes could potentially eliminate invasive breast cancer and destroy VM channels. Evaluations were made in human invasive breast cancer cells and their xenografts in nude mice. The results showed that the targeting epirubicin plus quinacrine liposomes could enhance the accumulation and uptake of the drugs in cancer tissues, kill cancer cells directly, activate apoptotic enzymes, destroy the VM channels and downregulate the VM channel-forming marker molecules (EphA2, FAK, PI3K, MMP 9, MMP 14, VE-Cad and HIF-α), thereby exhibiting a strong overall anticancer efficacy. The targeting epirubicin plus quinacrine liposomes provided a promising strategy to treat invasive breast cancer and to prevent the relapse arising from VM channels after chemotherapy.

Multifunctional liposomes loaded with paclitaxel and artemether for treatment of invasive brain glioma.

Invasive brain glioma is the most lethal type of cancer and is highly infiltrating. This leads to an extremely poor prognosis and makes complete surgical removal of the tumor virtually impossible. Non-penetration of therapeutic drugs across the blood-brain barrier (BBB), brain cancer stem cells (CSCs), and brain cancer vasculogenic mimicry (VM) results in relapse after surgical and radio therapy. We developed a functional targeting chemotherapy for transporting drugs across the BBB, destroying VM channels, and eliminating CSCs and cancer cells in the brain. The studies were undertaken on brain glioma cells in vitro and in brain glioma-bearing rats. Using paclitaxel as the anticancer drug and artemether as the regulator of apoptosis and inhibitor of VM channels, a kind of functional targeting paclitaxel plus artemether liposomes was developed by modifying two new functional materials: a mannose-vitamin E derivative conjugate (MAN-TPGS1000) and a dequalinium-lipid derivative conjugate (DQA-PEG2000-DSPE). The transport mechanism across the BBB was associated with receptor-mediated endocytosis by MAN-TPGS1000 conjugate via glucose transporters and adsorptive-mediated endocytosis by DQA-PEG2000-DSPE conjugate via electric charge-based interactions. The efficacy was related to the destruction of VM channels by regulating VM indicators, as well as the induction of apoptosis in brain cancer cells and CSCs by activating apoptotic enzymes and pro-apoptotic proteins and inhibiting anti-apoptotic proteins. These data suggest that the chemotherapy using functional targeting paclitaxel plus artemether liposomes could provide a new strategy for treating invasive brain glioma.

Targeting drug delivery systems for circumventing multidrug resistance of cancers.

Multidrug resistance is a major obstacle to successful chemotherapy of cancer. To overcome multidrug resistance, our research is to develop new liposome and nanomicelle delivery systems. Investigations are focusing on certain aspects, including resistant cancer cell membranes, cancer stem cells, mitochondria, apoptosis genes, vasculogenic mimicry and heterogeneity of cancer cells. Evaluations have been performed on cancer cells, cancer spheroids and cancer animal models. These nanoscale formulations demonstrated an enhanced chemotherapy efficacy in resistant cancer and cancer stem cells in vitro and in vivo.