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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Orienti, Isabella Salvati, Valentina Sette, Giovanni Zucchetti, Massimo Bongiorno-Borbone, Lucilla Peschiaroli, Angelo Zolla, Lello Francescangeli, Federica Ferrari, Mariella Matteo, Cristina Bello, Ezia Di Virgilio, Antonio Falchi, Mario De Angelis, Maria Laura Baiocchi, Marta Melino, Gerry De Maria, Ruggero Zeuner, Ann Eramo, Adriana |
| Abstract | Background An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials. Methods Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy. Results Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent. Conclusion Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin. |
| Related Links | https://jeccr.biomedcentral.com/counter/pdf/10.1186/s13046-019-1383-9.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17569966 |
| DOI | 10.1186/s13046-019-1383-9 |
| Journal | Journal of Experimental & Clinical Cancer Research |
| Issue Number | 1 |
| Volume Number | 38 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-08-22 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Immunology Apoptosis Oncology Fenretinide Bioavailability Solubility Antitumour activity Cancer stem cells Solid tumours Drug delivery Pharmacokinetics Cancer therapy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology Cancer Research |
| Journal Impact Factor | 11.4/2023 |
| 5-Year Journal Impact Factor | 11.4/2023 |
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