Cooperative dual-activity targeted nanomedicine for specific effective prostate cancer therapy
Journal
ACS Nano
Journal Volume
6
Journal Issue
2
Pages
1795-1805
Date Issued
2012
Author(s)
H-W Yang
M-Y Hua
H-L Liu
R-Y Tsai
C-K Chuang
P-C Chu
P-Y Wu
Y-H Chang
H-C Chuang
K-J Yu
S-T Pang
H-W Yang
M-Y Hua
H-L Liu
R-Y Tsai
C-K Chuang
P-C Chu
P-Y Wu
Y-H Chang
H-C Chuang
K-J Yu
S-T Pang
Abstract
A key issue in cancer therapy is how to enhance the tumor-targeting efficacy of chemotherapeutic agents. In this study, we developed a cooperative dual-targeted delivery platform for paclitaxel (PTX) that has potential application as a powerful prostate cancer treatment. The nanomedicine was prepared by first conjugating PTX to nontoxic high-magnetization nanocarriers which can be actively guided and targeted by an external magnet. Next, the surface was functionalized with carboxylated o-(2-aminoethyl)polyethyleneglycol (NH(2)-EPEG-COOH) to enable uptake by the reticuloendothelial system. Antiprostate-specific membrane antigen antibodies (APSMAs) were then conjugated onto the carrier to recognize the extracellular domain of the prostate-cancer specific membrane antigen (PSMA), thus binding to cancer cells as a secondary active targeting mechanism. We found a significant enhancement of PTX concentration at the tumor site by nearly 20-fold. In addition, the drug half-life was prolonged more than 4.1-fold (from 24 to 99 h) at 37 °C. Low-dose (4.5 mg/kg) injection of the dual-targeted therapeutic nanomedicine in the presence of magnetic targeting significantly prolonged the median survival of nude mice from 35 to 58 days compared to mice that received a high dose (6 mg/kg) of free PTX. This report demonstrates the potential utility of targeted nanomedicine in the clinical treatment of cancer.
SDGs
Type
journal article