Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy
Abstract
Abstract The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, it is shown that self‐assembled peptide amphiphile (PA) nanostructures can dynamically interact with endogenous biomolecules and take advantage of naturally occurring processes to target a broad range of solid tumors. In circulation, self‐assembled PA nanostructures disassemble and reassemble mainly with lipoproteins, which prolongs blood circulation and dramatically improves tumor accumulation and retention. Mechanistic studies suggested that PAs internalize into cancer cells by assembling with their cell membranes and independently of specific receptors. By exploiting these interactions, a PA developed in this study (namely Self‐Assembly ‐ Glutamic acid, SA‐E) demonstrates specific accumulation in various xenograft, syngeneic, patient‐derived xenograft, or transgenic rodent models. In addition, SA‐E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA‐E represents a promising platform for broad applications in cancer imaging and therapy.
Article Details
Authors (20)
Li Xiang
Morgan R. Stewart
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Kailin Mooney
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Mingchong Dai
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Samuel Drennan
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Samantha Holland
Neuro‐Oncology Blood‐Brain Barrier Program Oregon Health and Science University Portland Oregon 97239 USA
Arnaud Quentel
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Sinan Sabuncu
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Benjamin R. Kingston
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Isabel J. Dengos
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Karla Bonic
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Florian Goncalves
Xin Yi
Key Laboratory of Crop Integrated Pest Management in South China, Ministry of Agriculture, Department of Pesticide Science, College of Plant Protection, South China Agricultural University
Michael I. Henderson
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Srivathsan Ranganathan
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Bruce P. Branchaud
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA
Leslie L. Muldoon
Neuro‐Oncology Blood‐Brain Barrier Program Oregon Health and Science University Portland Oregon 97239 USA
Ramon F. Barajas Jr
Advanced Imaging Research Center Oregon Health and Science University Portland Oregon 97239 USA
Jared M. Fischer
Adem Yildirim
CEDAR Knight Cancer Institute School of Medicine Oregon Health and Science University Portland Oregon 97201 USA