PAMAM Dendrimer-Based Multifunctional Conjugate for Cancer Therapy: Synthesis, Characterization, and Functionality
- 13 January 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 7 (2), 572-579
- https://doi.org/10.1021/bm0506142
Abstract
Poly(amidoamine) (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized. The primary amino groups on the surface of the generation 5 (G5) PAMAM dendrimer were neutralized through partial acetylation, providing enhanced solubility of the dendrimer (in conjugation of FITC (fluorescein isothiocyanate)) and preventing nonspecific targeting interactions (in vitro and in vivo) during delivery. The functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and paclitaxel (taxol, a chemotherapeutic drug) were conjugated to the remaining nonacetylated primary amino groups. The appropriate control dendrimer conjugates have been synthesized as well. Characterization of the G5 PAMAM dendrimer and its nanosize conjugates, including the molecular weight and number of primary amine groups, has been determined by multiple analytical methods such as gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), potentiometric titration, high-performance liquid chromatography (HPLC), and UV spectroscopy. These multifunctional dendrimer conjugates have been tested in vitro for targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. We present here the synthesis, characterization, and functionality of these dendrimer conjugates.Keywords
This publication has 11 references indexed in Scilit:
- Poly(amidoamine) Dendrimer-Based Multifunctional Engineered Nanodevice for Cancer TherapyJournal of Medicinal Chemistry, 2005
- Targeting and Inhibition of Cell Growth by an Engineered Dendritic NanodeviceJournal of Medicinal Chemistry, 2005
- Mathematical Description of Dendrimer StructureJournal of Computational and Theoretical Nanoscience, 2004
- Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancerBritish Journal of Cancer, 2004
- A Novel Approach of Water-Soluble Paclitaxel Prodrug with No Auxiliary and No Byproduct: Design and Synthesis of IsotaxelJournal of Medicinal Chemistry, 2003
- Acetylation of Poly(amidoamine) DendrimersMacromolecules, 2003
- Dendritic polymer macromolecular carriers for drug deliveryCurrent Opinion in Chemical Biology, 2002
- Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applicationsDrug Discovery Today, 2001
- Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2New England Journal of Medicine, 2001
- A New Class of Polymers: Starburst-Dendritic MacromoleculesPolymer Journal, 1985