Polyisoprenoyl gemcitabine conjugates self assemble as nanoparticles, useful for cancer therapy

Maksimenko, Andrei; Mougin, Julie; Mura, Simona; Śliwiński, Éric; Lepeltier, Élise; Bourgaux, Claudie; Lepetre, Sinda; Zouhiri, Fatima; Desmaële, Didier; Couvreur, Patrick

doi:10.1016/j.canlet.2012.08.023

Cited by 67 publications

(61 citation statements)

References 23 publications

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“…Classification of the anticancer drugs, lipids used for their derivatization and the nanoscale drug delivery system based on these prodrugs are reported in Table 1. A C C E P T E D M A N U S C R I P T Liposomes [37][38][39] Stearic acid C18 (stearoyl) Liposomes [36][37][38][39] Micelles [40,41] Polymer nanoparticles [42] Solid lipid nanoparticles [43][44][45][46] Self-assembled nanoparticles [47] Squalene Nanoparticles [50][51][52][53] [54-57, 59-63, 66, 67] Isoprenoids (monoisoprenoyl, geranyl farnesyl,polyisoprenoyl) Nanoparticles [68,69] Squalene Liposomes [58] Gemcitabine monofosfate Squalene Nanoparticles [64,65] Cytosine arabinoside Oleic acid Palmitic acid Liposomes [73] Cholesterol Liposomes [74] Glycerol substituted Liposomes [75] Phospholipids Thioether lipids (1-Salkylthioglycerols) Micelles [76] Squalene Liposomes [77][78] 5-fluorouracil Stearic acid Solid lipid nanoparticles [79] Floxuridine Octanoic acid; palmitic acid Liposomes [80][81][82] Octanoic acid; Solid lipid nanoparticles [84] Capecitabine Palmitic acid, Phytic acid,Oleic acid, Stearic acid, Linoleic acid, Linolenic acid Solid lipid nanoparticles, cubosomes, gyroids, double diamonds [85][86]…”

Section: Nanoparticulate Lipid Prodrugs For Drug Deliverymentioning

confidence: 99%

“…Others polyisoprenoid structures have been tested as prodrug building block for Gem, either molecular (e.g., monoisoprenyl, geranylacetyl, prenylacetyl, farnesylacetyl) [68] or macromolecular such as short, well-defined polyisoprene (PI) chains [69]. It was shown that modulation of the polyisoprenoyl chain length has a great effect of the antitumor activity [68].…”

Section: Antimetabolite Agentsmentioning

confidence: 99%

See 1 more Smart Citation

Lipid prodrug nanocarriers in cancer therapy

Mura

Bui

Couvreur

et al. 2015

Journal of Controlled Release

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101

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Section: Nanoparticulate Lipid Prodrugs For Drug Deliverymentioning

confidence: 99%

Section: Antimetabolite Agentsmentioning

confidence: 99%

Lipid prodrug nanocarriers in cancer therapy

Mura

Bui

Couvreur

et al. 2015

Journal of Controlled Release

Self Cite

101

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“…19 In addition, nano-encapsulation also improves the drug's antitumor activity 17 by making the tumor cells more sensitive to the drug. 16 In this line of research, using CML stem cells, Palamà et al have reported that packaging of imatinib mesylate into a biodegradable carrier based on polyelectrolyte microcapsules increased the drug's retention effects and antitumor activity, while improving the ex vivo purging of malignant progenitors from patient autografts. 24 Both the reduction in off-target cardiotoxicity and increased antitumor activity could be attributed to the gradual release of imatinib mesylate, or reduced exposure of imatinib mesylate to the heart tissue, as it is encapsulated inside the nanoparticles.…”

Section: Cardiac Histopathologymentioning

confidence: 99%

“…Drug-encapsulated nanoparticles with sustained release properties have been attempted to minimize off-target toxicity of many cancer drugs, [15][16][17][18][19][20] including imatinib mesylate. [21][22][23] While the nano-encapsulation of imatinib mesylate improves its antitumor activity, 23,24 it is also demonstrated to minimize the cytotoxicity of the drug to normal cells.…”

Section: Introductionmentioning

confidence: 99%

Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

Marslin¹,

Revina²,

Khandelwal³

et al. 2015

IJN

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Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide- co -glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.

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“…This technology is simple and avoids the use of an organic solvent. Moreover, the high drug loading limits the amount of excipients that enter in the organism and therefore their potential toxicity (14,15). In spite of these advantages and although the system is ready to undergo clinical trial, funding is still missing.…”

Section: The Long Way From the Lab Bench To The Patientmentioning

confidence: 99%

Is the translational approach becoming a reality in nanomedicine?

Malhaire

Lagarce

2015

European Journal of Nanomedicine

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This paper summarizes the key points discussed at the international conference held in Angers (France) on translational nanomedicine. During 3 days, more than 150 attendees presented their works and discussed through plenary sessions on how to translate to the clinics the discoveries found at lab scale. The importance of interdisciplinary works has been emphasized. New promising strategies inspired by biology were presented, such as bacteriophage associated silicon particles (BASP) in cancer therapy. Green nanotechnology, which limits the use of potentially toxic excipients to the benefit of natural compounds, is growing. Although there are various financial helps for the research and the training of next generations of researchers, the difficulties to find funding to go to the clinics has been illustrated by the squalene-conjugated nanoparticles that find no industrial support. Large-scale production of nanomedicines is also challenging to implement and pharmaceutical companies are developing new large-scale production tools to reach the patient bedside. Last but not least, regulation requirements and patenting have been forced to evolve and adapt to these particular vectors. As a conclusion, transversal collaborative research and a design of nanomedicine based on simplicity are two important levers to help these promising drugs to reach the patient.

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Polyisoprenoyl gemcitabine conjugates self assemble as nanoparticles, useful for cancer therapy

Cited by 67 publications

References 23 publications

Lipid prodrug nanocarriers in cancer therapy

Lipid prodrug nanocarriers in cancer therapy

Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

Is the translational approach becoming a reality in nanomedicine?

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