Antibody Targeting of Camptothecin-Loaded PLGA Nanoparticles to Tumor Cells

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• 作者：Paul A. McCarron ; Waleed M. Marouf ; Derek J. Quinn ; Francois Fay ; Roberta E. Burden ; Shane A. Olwill ; Christopher J. Scott
• 刊名：Bioconjugate Chemistry
• 出版年：2008
• 出版时间：August 2008
• 年：2008
• 卷：19
• 期：8
• 页码：1561-1569
• 全文大小：285K
• 年卷期：v.19,no.8(August 2008)
• ISSN：1520-4812

文摘

Antibody targeting of drug substances can improve the efficacy of the active molecule, improving distribution and concentration of the drug at the site of injury/disease. Encapsulation of drug substances into polymeric nanoparticles can also improve the therapeutic effects of such compounds by protecting the molecule until its action is required. In this current study, we have brought together these two rationales to develop a novel immuno-nanoparticle with improved therapeutic effect against colorectal tumor cells. This nanoparticle comprised a layer of peripheral antibodies (Ab) directed toward the Fas receptor (CD95/Apo-1) covalently attached to poly(lactide-co-glycolide) nanoparticles (NP) loaded with camptothecin. Variations in surface carboxyl density permitted up to 48.5 μg coupled Ab per mg of NP and analysis of nanoparticulate cores showed efficient camptothecin loading. Fluorescence visualization studies confirmed internalization of nanoconstructs into endocytic compartments of HCT116 cells, an effect not evident in NP without superficial Ab. Cytotoxicity studies were then carried out against HCT116 cells. After 72 h, camptothecin solution resulted in an IC₅₀ of 21.8 ng mL⁻¹. Ab-directed delivery of NP-encapsulated camptothecin was shown to be considerably more effective with an IC₅₀ of 0.37 ng mL⁻¹. Calculation of synergistic ratios for these nanoconstructs demonstrated synergy of pharmacological relevance. Indeed, the results in this paper suggest that the attachment of anti-Fas antibodies to camptothecin-loaded nanoparticles may result in a therapeutic strategy that could have potential in the treatment of tumors expressing death receptors.