Novel Isoprenoyl Nanoassembled Prodrug for Paclitaxel Delivery
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- 作者：Simona Mura ; Fatima Zouhiri ; Stephanie Lerondel ; Andrei Maksimenko ; Julie Mougin ; Claire Gueutin ; Davide Brambilla ; Joachim Caron ; Eric Sliwinski ; Alain LePape ; Didier Desmaele ; Patrick Couvreur
- 刊名：Bioconjugate Chemistry
- 出版年：2013
- 出版时间：November 20, 2013
- 年：2013
- 卷：24
- 期：11
- 页码：1840-1849
- 全文大小：431K
- 年卷期：v.24,no.11(November 20, 2013)
- ISSN：1520-4812
文摘
A new paclitaxel (Ptx) prodrug was designed by coupling a single terpene unit (MIP) to the hydroxyl group in position 2鈥?of the drug molecule. Using a squalene derivative of polyethylene glycol (SQ-PEG) as surface active agent, the resulting bioconjugate (PtxMIP) self-assembled in water leading to the formation of stable nanoparticles (PtxMIP_SQ-PEG NPs) with an impressively high drug loading (82%). In vivo, the anticancer activity of this novel Ptx nanoassembled prodrug was compared to the conventional Cremophor-containing formulation (Taxol) on a murine model of breast cancer lung metastasis induced by intravenous injection of 4T1 tumor cells, genetically modified to stably express firefly luciferase. Cell growth was assessed noninvasively by bioluminescence imaging (BLI) which enabled monitoring tumor metastatic burden in the same animals. PtxMIP_SQ-PEG nanoparticles slowed metastatic spread and were better tolerated than the Cremophor-containing formulation (i.e., free drug), thus demonstrating the potential of terpene-based nanoassembled prodrugs in the improvement of the therapeutic index of Ptx in balb/c mice.