Plasma membrane targeting by short chain sphingolipids inserted in liposomes improves anti-tumor activity of mitoxantrone in an orthotopic breast carcinoma xenograft model

Pedrosa, Lília R. Cordeiro; Tellingen, Olaf van; Soullié, Thomas; Seynhaeve, Ann L.B.; Eggermont, Alexander M.M.; Hagen, Timo L.M. ten; Verheij, Marcel; Koning, Gerben A.

doi:10.1016/j.ejpb.2015.05.003

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…The above-mentioned resistance to chemotherapy is due not only to dysregulation of ceramide and S1P metabolism, but also to the presence of protein mediators and their signaling actions. According to Gatt et al, increased expression of ceramide transporting proteins (CERT) and their intracellular accumulation associated with S1P is a possible cause of ovarian cancer resistance to chemotherapy with platinum derivatives [34][35][36].…”

Section: Ovarian Cancer Patient (N = 74)mentioning

confidence: 99%

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Knapp

Bodnar

Błachnio-Zabielska

et al. 2017

Gynecologic Oncology

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Section: Ovarian Cancer Patient (N = 74)mentioning

confidence: 99%

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Knapp

Bodnar

Błachnio-Zabielska

et al. 2017

Gynecologic Oncology

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“…In addition to DXR, liposomal preparations enriched with SCS were also exploited for loading of Mitoxantrone (MTO), an anthracenedione antineoplastic antibiotic that is used in the treatment of acute leukemia, lymphoma, prostate, and breast cancer [ 40 , 52 ]. Similarly to DXR, MTO also needs to reach the cell nucleus to condensate DNA and inhibits replication and RNA transcription.…”

Section: Enhancing Cellular Drug Delivery By Short Chain Sphingolipidsmentioning

confidence: 99%

“…Importantly, while only a marginal nuclear delivery located at the tumor periphery was observed following administration of free drug, the MTO fluorescence after administration of liposomal preparations was observed in more deep regions of the tumor. Both SCS-liposomal MTO formulations were further evaluated in vivo, with respect to PK and the anti-tumor activity in a mouse model of MDAMB-231 breast carcinoma [ 40 ]. At a single dose of 5 mg/kg MTO, due to the wide distribution throughout the body and fast clearance rate of free drug, MTO was not detectable in the blood at selected time points after administration of free MTO.…”

Section: Enhancing Cellular Drug Delivery By Short Chain Sphingolipidsmentioning

confidence: 99%

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

et al. 2022

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At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.

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“…Triglyceride incorporation increases the membrane fluidity and lamellarity of liposomes composed of saturated phosphatidylcholine (PC), thereby improving their hydrophobic drug–incorporation capacity (Hong et al., 2015 ). Insertion of short-chain sphingolipids in the liposomal bilayer improves intracellular drug delivery to tumor cells through membrane permeabilization (Cordeiro Pedrosa et al., 2015 ). Bile salt enrichment in liposomal bilayers increases liposomal stability in the gastrointestinal tract and enhances the oral absorption of incorporated drugs (Niu et al., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs

et al. 2017

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Studies have shown that insertion of oleic acid into lipid bilayers can modulate the membrane properties of liposomes so as to improve their function as drug carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor agent currently undergoing clinical trials, is a derivative of oleic acid, we explored the possibility of developing 2OHOA-inserted liposomes as a multifunctional carrier of antitumor drugs in the present study. The insertion of 2OHOA into lipid bilayers was confirmed by surface charge determination and differential scanning calorimetry. 2OHOA insertion greatly decreased the order of dimyristoylphosphatidylcholine packing, produced a nanosized (<100 nm) dispersion, and improved the colloidal stability of liposomes during storage. Moreover, 2OHOA-inserted liposome forms exhibited greater growth inhibitory activity against cancer cells compared with free 2OHOA, and the growth-inhibitory activity of liposomal 2OHOA was selective for tumor cells. 2OHOA insertion greatly increased the liposome-incorporated concentration of hydrophobic model drugs, including mitoxantrone, paclitaxel, and all-trans retinoic acid (ATRA). The in vitro anticancer activity of ATRAincorporated/2OHOA-inserted liposomes was significantly higher than that of ATRA-incorporated conventional liposomes. In a B16-F10 melanoma syngeneic mouse model, the tumor growth rate was significantly delayed in mice treated with ATRA-incorporated/2OHOA-inserted liposomes compared with that in the control group. Immunohistochemical analyses revealed that the enhanced antitumor activity of ATRA-incorporated/2OHOA-inserted liposomes was due, at least in part, to increased induction of apoptosis. Collectively, our findings indicate that 2OHOA-inserted liposomes exhibit multiple advantages as antitumor drug carriers, including the ability to simultaneously deliver two anticancer drugs -2OHOA and incorporated drug -to the tumor tissue.ARTICLE HISTORY

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Plasma membrane targeting by short chain sphingolipids inserted in liposomes improves anti-tumor activity of mitoxantrone in an orthotopic breast carcinoma xenograft model

Cited by 10 publications

References 46 publications

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer drugs

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