Multifunctional Synthetic Poly(l-Glutamic Acid)–Based Cancer Therapeutic and Imaging Agents

Marites P Melancon,Chun Li

doi:10.2310/7290.2011.00007

Abstract

Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers that have been increasingly studied as efficient carriers for drugs and imaging agents. Synthetic biocompatible polymers have been used to improve the efficacy of both small-molecular-weight therapeutics and imaging agents. Furthermore, multiple targeted anticancer agents and/or imaging reporters can be attached to a single polymer chain, allowing multifunctional and/or multimodality therapy and molecular imaging. Having both an anticancer drug and an imaging reporter in a single polymer chain allows noninvasive real-time visualization of the pharmacokinetics of polymeric drug delivery systems, which can uncover and explain the complicated mechanisms of in vivo drug delivery and their correlation to pharmacodynamics. This review examines the use of the synthetic biocompatible polymer poly(L-glutamic acid) (PG) as an efficient carrier of cancer therapeutics and imaging agents. This review summarizes and updates our recent research on the use of PG as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL), the combination of PG-TXL with radiotherapy, mechanisms of action of PG-TXL, and noninvasive visualization of in vivo delivery of polymeric conjugates with contrast-enhanced magnetic resonance imaging, optical imaging, and multimodality imaging.

Highlights

Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers that have been increasingly studied as efficient carriers for drugs and imaging agents
We summarize and update our recent research on the use of poly(Lglutamic acid) (PG) as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL), the combination of PG-TXL with radiotherapy, mechanisms of action of PG-TXL, and noninvasive visualization of in vivo delivery of polymeric conjugates with contrastenhanced magnetic resonance imaging (MRI), optical imaging, and multimodality imaging
The formulation of PG-TXL used in clinical studies has a median molecular weight of PG-TXL equal to 48,000 Da and about 37% paclitaxel by weight, which is equivalent to approximately one paclitaxel molecule for every 11 glutamic acid units in each PG polymer chain.[67]

Summary

Introduction

Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers that have been increasingly studied as efficient carriers for drugs and imaging agents. Modern polymer chemistry has led to the generation of a number of biocompatible polymer structures, including branched,[1] graft,[2,3] multivalent polymers[4] and dendrimers.[5,6] These biomedical macromolecules, which vary in size from 10 to 1,000 nm,[7] have unique pharmacokinetic properties, including prolonged blood circulation, enhanced tissue retention, and preferential accumulation in lesions with leaky vasculature.[8] For these reasons, polymers have since been used as effective drug delivery devices.[7,9] Drugs or any therapeutic agent of interest are normally encapsulated, adsorbed, or conjugated on the surface.[10] Delivery of these drugs is accomplished by using the natural characteristics of the tissue or organ, such as the leaky. Active targeting of a therapeutic agent, in contrast to passive targeting, is achieved by conjugating the therapeutic agent or the carrier system to a tissue- or cell-specific ligand.[10,11]

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