Combination of Small Molecule Prodrug and Nanodrug Delivery: Amphiphilic Drug–Drug Conjugate for Cancer Therapy
Top Cited Papers
- 7 August 2014
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 136 (33), 11748-11756
- https://doi.org/10.1021/ja505212y
Abstract
All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug–drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir–Cb conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir–Cb ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.Keywords
Funding Information
- Ministry of Science and Technology of the People's Republic of China (2011CB933101, 2012CB821500, 2013CB834506)
- National Natural Science Foundation of China (21025417, 91127047)
This publication has 49 references indexed in Scilit:
- Nanomaterials for Drug DeliveryScience, 2012
- Self‐Assembly of Hyperbranched Polymers and Its Biomedical ApplicationsAdvanced Materials, 2010
- The in vitro biocompatibility of self-assembled hyperbranched copolyphosphate nanocarriersBiomaterials, 2010
- Soluble Polymer Carriers for the Treatment of Cancer: The Importance of Molecular ArchitectureAccounts of Chemical Research, 2009
- Nanomedicine—Challenge and PerspectivesAngewandte Chemie-International Edition, 2009
- Polymeric nanomedicine for cancer therapyProgress in Polymer Science, 2008
- Modern trends in polymer bioconjugates designProgress in Polymer Science, 2008
- Polymer TherapeuticsScience, 2007
- Anticancer Polymeric NanomedicinesPolymer Reviews, 2007
- Designing dendrimers for biological applicationsNature Biotechnology, 2005