Targeted Drug Delivery Utilizing Protein-Like Molecular Architecture

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• 作者：Evonne M. Rezler ; David R. Khan ; Janelle Lauer-Fields ; Mare Cudic ; Diane Baronas-Lowell ; Gregg B. Fields
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：April 25, 2007
• 年：2007
• 卷：129
• 期：16
• 页码：4961 - 4972
• 全文大小：648K
• 年卷期：v.129,no.16(April 25, 2007)
• ISSN：1520-5126

文摘

Nanotechnology-based drug delivery systems (nanoDDSs) have seen recent popularity due totheir favorable physical, chemical, and biological properties, and great efforts have been made to targetnanoDDSs to specific cellular receptors. CD44/chondroitin sulfate proteoglycan (CSPG) is among thereceptors overexpressed in metastatic melanoma, and the sequence to which it binds within the type IVcollagen triple-helix has been identified. A triple-helical "peptide-amphiphile" (mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277 PA), whichbinds CD44/CSPG, has been constructed and incorporated into liposomes of differing lipid compositions.Liposomes containing distearoyl phosphatidylcholine (DSPC) as the major bilayer component, in combinationwith distearoyl phosphatidylglycerol (DSPG) and cholesterol, were more stable than analogous liposomescontaining dipalmitoyl phosphatidylcholine (DPPC) instead of DSPC. When dilauroyl phosphatidylcholine(DLPC):DSPG:cholesterol liposomes were prepared, monotectic behavior was observed. The presence ofthe mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277 PA conferred greater stability to the DPPC liposomal systems and did not affect thestability of the DSPC liposomes. A positive correlation was observed for cellular fluorophore delivery bythe mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277 PA liposomes and CD44/CSPG receptor content in metastatic melanoma andfibroblast cell lines. Conversely, nontargeted liposomes delivered minimal fluorophore to these cellsregardless of the CD44/CSPG receptor content. When metastatic melanoma cells and fibroblasts weretreated with exogeneous mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277, prior to incubation with mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277 PA liposomes, topotentially disrupt receptor/liposome interactions, a dose-dependent decrease in the amount of fluorophoredelivered was observed. Overall, our results suggest that PA-targeted liposomes can be constructed andrationally fine-tuned for drug delivery applications based on lipid composition. The selectivity of mages/gifchars/alpha.gif" BORDER=0>1(IV)1263-1277 PA liposomes for CD44/CSPG-containing cells represents a targeted-nanoDDS with potentialfor further development and application.