IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer.
Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.
Department of Surgery and Radiology, Emory University School of Medicine, Atlanta, Georgia.
Hongyu
H
Zhou
Department of Surgery and Radiology, Emory University School of Medicine, Atlanta, Georgia.
Weiping
W
Qian
University of Southern California Norris Comprehensive Cancer Center, Children's Hospital Los Angeles, Los Angeles, CA.
Fatih M
FM
Uckun
Department of Surgery and Radiology, Emory University School of Medicine, Atlanta, Georgia; Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, China.
Zhiyang
Z
Zhou
Department of Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia.
Liya
L
Wang
Ocean Nanotech, LLC, San Diego, CA.
Andrew
A
Wang
Department of Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia.
Hui
H
Mao
Department of Surgery and Radiology, Emory University School of Medicine, Atlanta, Georgia; Department of Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia.
Lily
L
Yang
IGF1R targeted cancer therapy; Image-guided cancer therapy; MRI; Pancreatic cancer; Patient derived xenografts; Theranostic nanoparticles; Tumor microenvironment