Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer

Booser, Daniel J.; Esteva, Francisco J.; Rivera, Edgardo; Valero, Vicente; Esparza-Guerra, Laura; Priebe, Waldemar; Hortobágyi, Gabriel N.

doi:10.1007/s00280-002-0464-0

Cited by 66 publications

(21 citation statements)

References 2 publications

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“…Particulate drug delivery systems such as polymeric microspheres (Liu et al, 2001), nanoparticles (de Verdiere et al 1997;Moghimi and Hunter, 2000), liposomes (Thierry et al, 1993;Romsicki and Sharom, 1999;Booser et al, 2002), and solid lipid nanoparticles (SLNs) (Wong et al, 2004(Wong et al, , 2005 offer great promise to achieve the aforementioned goal. Particulate systems are well known to be able to deliver drugs with higher efficiency with fewer adverse side effects (Booser et al, 2002;Lamprecht et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Because cytotoxic drugs typically carry numerous dose-limiting normal tissue side effects (Tipton, 2003), it is generally impractical to overcome this form of drug resistance simply by increasing the drug dose. To improve the therapeutic ratio of cancer chemotherapy, it is critical to establish alternative approaches that may improve accumulation and prolong retention of cytotoxic drugs in drug-resistant cancer cells without causing additional normal tissue side effects.Particulate drug delivery systems such as polymeric microspheres (Liu et al, 2001), nanoparticles (de Verdiere et al 1997;Moghimi and Hunter, 2000), liposomes (Thierry et al, 1993;Romsicki and Sharom, 1999;Booser et al, 2002), and solid lipid nanoparticles (SLNs) (Wong et al, 2004(Wong et al, , 2005 offer great promise to achieve the aforementioned goal. Particulate systems are well known to be able to deliver drugs with higher efficiency with fewer adverse side effects (Booser et al, 2002;Lamprecht et al, 2005).…”

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confidence: 99%

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A Mechanistic Study of Enhanced Doxorubicin Uptake and Retention in Multidrug Resistant Breast Cancer Cells Using a Polymer-Lipid Hybrid Nanoparticle System

Wong

Bendayan²,

Rauth³

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

334

213

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The objectives of this study were to evaluate the potential of a polymer-lipid hybrid nanoparticle (PLN) system to enhance cellular accumulation and retention of doxorubicin (Dox), a widely used anticancer drug and an established P-glycoprotein (Pgp) substrate, in Pgp-overexpressing cancer cell lines and to explore the underlying mechanisms. Nanoparticles containing Dox complexed with a novel anionic polymer (Dox-PLN) were prepared using an ultrasound method. Two Pgp-overexpressing breast cancer cell lines (a human cell line, MDA435/LCC6/ MDR1, and a mouse cell line, EMT6/AR1) were used to investigate the effect of nanoparticles on cellular uptake and retention of Dox. Endocytosis inhibition studies and fluorescence microscopic imaging were performed to elucidate the mechanisms of cellular drug uptake. Treatment of Pgp-overexpressing cell lines with Dox-PLNs resulted in significantly enhanced Dox uptake and more substantial increases in drug retention after the end of treatment compared with free Dox solutions (p Ͻ 0.05). Fluorescence microscopic images showed improved nuclear localization of Dox and uptake of lipid when the drug was delivered in the Dox-PLN form to MDA435/LCC6/ MDR1 cells. Endocytosis inhibition studies revealed that phagocytosis is an important pathway in the membrane permeability of the nanoparticles. These findings suggest that some of the Dox physically associated with the nanoparticles bypass the membrane-associated Pgp when delivered as DoxPLNs, and in this form, the drug is better retained within the Pgp-overexpressing cells than the free drug. The present study suggests a new mechanism for overcoming drug resistance in Pgp-overexpressing tumor cells using lipid-based nanoparticle formulations.Chemotherapy with the use of cytotoxic drugs is commonly implemented in the management of many cancer types, e.g., breast cancers (Skeel, 2003;Tack et al., 2004). However, suboptimal therapeutic responses associated with multidrug resistance (MDR) frequently occur (Longley and Johnston, 2005). Overexpression of P-glycoprotein (Pgp) is one of the prominent mechanisms that contribute to the MDR phenotype (Endicott and Ling, 1989;Gottesman, 2002). Pgp is a 170-kDa membrane-associated glycoprotein that may actively extrude several substrates, including a variety of cytotoxic drugs such as doxorubicin (Dox), from cell cytoplasm to outside of plasma membrane, thus lowering the effective drug concentrations within the cells (Endicott and Ling, 1989;Gottesman, 2002). Because cytotoxic drugs typically carry numerous dose-limiting normal tissue side effects (Tipton, 2003), it is generally impractical to overcome this form of drug resistance simply by increasing the drug dose. To improve the therapeutic ratio of cancer chemotherapy, it is critical to establish alternative approaches that may improve accumulation and prolong retention of cytotoxic drugs in drug-resistant cancer cells without causing additional normal tissue side effects.Particulate drug delivery systems such as polymeric microspheres (...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

A Mechanistic Study of Enhanced Doxorubicin Uptake and Retention in Multidrug Resistant Breast Cancer Cells Using a Polymer-Lipid Hybrid Nanoparticle System

Wong

Bendayan²,

Rauth³

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

334

213

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“…98 Similar to SPI-077, a Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer had no detectable antitumor activity. 99 Although new liposomalbased drugs have been well studied in preclinical animal models, these liposomal pharmaceutical products may be unable to provide promising therapeutic effects in clinical trials. For future development of liposomal-based drugs, the comparison of drug circulation time in blood, drug accumulation in tissues, and possible toxicity between conventional vesicles and new generations of liposomes should be investigated in preclinical animal models.…”

Section: Future Approachesmentioning

confidence: 99%

Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy

Chang

Yeh²

2011

IJN

336

159

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Abstract:Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposomebased drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized.

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“…Increasing evidence has demonstrated that functionalized liposomes are able to maintain the nature of pegylated liposomes -which show enhanced permeability and retention (EPR) effects in tumor tissues -and to potentiate the killing effect in drug-resistant cancer and in cancer stem cells through varying mechanisms and signaling pathways. [20][21][22] In the present study, we prepared functional epirubicin liposomes modified with 1,2-distearoyl-sn-glycero-3 -phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG 2000 ) and dequalinium. The present study aimed to characterize the capability of these functional epirubicin liposomes to modulate mitochondria to eliminate refractory cancers.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Yan

et al. 2017

IJN

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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.

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Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer

Cited by 66 publications

References 2 publications

A Mechanistic Study of Enhanced Doxorubicin Uptake and Retention in Multidrug Resistant Breast Cancer Cells Using a Polymer-Lipid Hybrid Nanoparticle System

A Mechanistic Study of Enhanced Doxorubicin Uptake and Retention in Multidrug Resistant Breast Cancer Cells Using a Polymer-Lipid Hybrid Nanoparticle System

Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy

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

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