Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin, to treat cisplatin-resistant cervical cancer

Casagrande, Naike; Paoli, Monica De; Celegato, Marta; Borghese, Cinzia; Mongiat, Maurizio; Colombatti, Alfonso; Aldinucci, Donatella

doi:10.1016/j.ygyno.2013.08.041

Cited by 47 publications

(37 citation statements)

References 30 publications

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“…Thus, the toxic payload enters the cytoplasm bypassing active import, explaining the efficacy of lipoplatin against platinum-resistant tumors (6). Accordingly, we demonstrated that lipoplatin is active both in vitro and in vivo against cisplatin-resistant cervical cancer cells (8). Lipoplatin has an enhanced half-life circulation time in body fluids and tissues and can extravasate through the leaky tumor vasculature reaching concentrations 10-to 200-fold higher in the tumor or metastases than in the adjacent normal tissues.…”

Section: Introductionmentioning

confidence: 72%

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Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Casagrande

Celegato

Borghese

et al. 2014

Clinical Cancer Research

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Purpose: Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer; however, treatment is associated with tumor resistance and significant toxicity. Here we investigated the antitumoral activity of lipoplatin, one of the most promising liposomal platinum drug formulations under clinical investigation.Experimental Design: In vitro effects of lipoplatin were tested on a panel of ovarian cancer cell lines, sensitive and resistant to cisplatin, using both two-dimensional (2D) and 3D cell models. We evaluated in vivo the lipoplatin anticancer activity using tumor xenografts.Results: Lipoplatin exhibited a potent antitumoral activity in all ovarian cancer cell lines tested, induced apoptosis, and activated caspase-9, -8, and -3, downregulating Bcl-2 and upregulating Bax. Lipoplatin inhibited thioredoxin reductase enzymatic activity and increased reactive oxygen species accumulation and reduced EGF receptor (EGFR) expression and inhibited cell invasion. Lipoplatin demonstrated a synergistic effect when used in combination with doxorubicin, widely used in relapsed ovarian cancer treatment, and with the albumin-bound paclitaxel, Abraxane. Lipoplatin decreased both ALDH and CD133 expression, markers of ovarian cancer stem cells. Multicellular aggregates/spheroids are present in ascites of patients and most contribute to the spreading to secondary sites. Lipoplatin decreased spheroids growth, vitality, and cell migration out of preformed spheroids. Finally, lipoplatin inhibited more than 90% tumor xenograft growth with minimal systemic toxicity, and after the treatment suspension, no tumor progression was observed.

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Section: Introductionmentioning

confidence: 72%

“…Given the properties of lipoplatin to overcome cisplatin resistance and to induce low toxicity (6,8), this drug could represent a good alternative to cisplatin. The aim of our study was to analyze the efficacy of lipoplatin in the ovarian cancer setting.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Casagrande

Celegato

Borghese

et al. 2014

Clinical Cancer Research

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“…The study was conducted to analyze the antitumoral activity and mechanism of action of formulation in the ME-180 cervical cancer cell line and its cisplatin-resistant clone R-ME-180 and HeLa cells by means of cell proliferation assays, flow cytometry, ELISA assay, cell migration, spheroids, and tumor xenograft [43]. A novel heat-activated thermosensitive liposome formulation containing cisplatin was developed to release around 90% of the loaded drug within 5 min in mild heating conditions.…”

Section: Systemic Versus Localized Drug Delivery Systemsmentioning

confidence: 99%

“…No.Drug/antibodyType/composition of liposomesCell lines/animal/clinical modelsReference1.PaclitaxelStearyl amine-based positively charged multilayered liposomesHeLa cell lines[42]2.Cisplatin–ME-180 cervical cancer cell line, cisplatin-resistant clone R-ME-180 and HeLa cells[43]3.CisplatinHeat-activated thermosensitive liposome–[44]4.Doxorubicin–Cervical cancer patients[45]5.IL-2Anionic, cationic, and neutral liposomesINBL cells 6.DoxorubicinTransferrin (Tf)-conjugated stealth liposomes (Tf-SL-DOX)–[47]7.DoxorubicinLiposomes conjugated with folic acid and transferrinHeLa cells[48]8.IL-2Cationic liposome containingINBL cells induced tumor-containing immune-depressed CBA mice[49] …”

Section: Systemic Versus Localized Drug Delivery Systemsmentioning

confidence: 99%

Possible role of nanocarriers in drug delivery against cervical cancer

Gupta

2017

Nano Reviews & Experiments

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Introduction: Cervical cancer is the second most common cancer and the largest cancer killer among women in most developing countries including India. Although, various drugs have been developed for cervical cancer, treatment with these drugs often results in a number of undesirable side effects, toxicity and multidrug resistance (MDR). Also, the outcomes for cervical cancer patients remain poor after surgery and chemo radiation. Methods: A literature search (for drugs and delivery systems against cervical cancer) was performed on PubMed and through Google. The present review discuss about various methods including its current conventional treatment with special reference to recent advances in delivery systems encapsulating various anticancer drugs and natural plant products for targeting towards cervical cancer. The role of photothermal therapy, gene therapy and radiation therapy against cervical cancer is also discussed. Results: Systemic/targeted drug delivery systems including liposomes, nanoparticles, hydrogels, dendrimers etc. and localized drug delivery systems like cervical patches, films, rings etc. are safer than the conventional chemotherapy which has further been proved by the several drug delivery systems undergoing clinical trials. Conclusion: Novel approaches for the aggressive treatment of cervical cancer will optimistically result in decreased side effects as well as toxicity, frequency of administration of existing drugs, to overcome MDR and to increase the survival rates.

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“…Cells without the addition of MTT reagents were used as a blank control. The drug concentration causing 50% inhibition (IC 50 ) was calculated using the CalcuSyn software (Biosoft, Ferguson, MO) (Casagrande et al, 2013).…”

Section: In Vitro Cytotoxicity Studymentioning

confidence: 99%

Novel RGD containing, temozolomide-loading nanostructured lipid carriers for glioblastoma multiforme chemotherapy

Song

Mao

et al. 2015

Drug Delivery

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Context: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system. Efficient delivery of therapeutic molecules to the cells and tissues is a difficult challenge. Objective: Arginine-glycine-aspartic acid peptide (RGD)-modified nanostructured lipid carriers (NLCs) were used for the delivery of temozolomide (TMZ) into the GBM to provide a new paradigm in gliomatosis cerebri treatment. Methods:RGD-conjugated polyethylene glycol-b-distearoylphosphatidylethanolamine (PEG-DSPE) was synthesized. RGD containing, TMZ-loaded NLCs (RGD-TMZ/NLCs) were prepared. Their particle size, zeta potential, drug encapsulation efficiency (EE) and drug release behavior were evaluated. In vitro cytotoxicity study of TMZ/NLCs was tested in U87 malignant glioma cells (U87MG cells). In vivo antitumor efficacy of the carriers was evaluated on mice bearing GBM model. Results: The U87MG cells were successfully inhibited by RGD-TMZ/NLCs in vitro. RGD-TMZ/NLCs also displayed the highest antitumor efficacy in vivo than all the other formulations used for comparison. Conclusion: RGD-TMZ/NLCs were efficient in selective delivery of TMZ into U87MG cells, and inhibition efficacy is high. These RGD-modified vectors could be a superior drug delivery nanosystem to achieve therapeutic efficacy, and this research could be a new promising strategy for treatment in malignant gliomatosis cerebri.

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Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin, to treat cisplatin-resistant cervical cancer

Cited by 47 publications

References 30 publications

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Possible role of nanocarriers in drug delivery against cervical cancer

Novel RGD containing, temozolomide-loading nanostructured lipid carriers for glioblastoma multiforme chemotherapy

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