Multifunctional biodegradable polyacrylamide nanocarriers for cancer theranostics--a "see and treat" strategy.
We describe here the development of multifunctional nanocarriers, based on amine-functionalized biodegradable polyacrylamide nanoparticles (NPs), for cancer theranostics, including active tumor targeting, fluorescence imaging, and photodynamic therapy. The structural design involves adding primary amino groups and biodegradable cross-linkers during the NP polymerization, while incorporating photodynamic and fluorescent imaging agents into the NP matrix, and conjugating PEG and tumor-targeting ligands onto the surface of the NPs. The as-synthesized NPs are spherical, with an average diameter of 44 nm. An accelerated biodegradation study, using sodium hydroxide or porcine liver esterase, indicated a hydrogel polymer matrix chain collapse within several days. By using gel permeation chromatography, small molecules were detected, after the degradation. In vitro targeting studies on human breast cancer cells indicate that the targeted NPs can be transported efficiently into tumor cells. Incubating the multifunctional nanocarriers into cancer cells enabled strong fluorescence imaging. Irradiation of the photosensitizing drug, incorporated within the NPs, with light of a suitable wavelength, causes significant but selective damage to the impregnated tumor cells, but only inside the illuminated areas. Overall, the potential of polymeric-based NPs as biodegradable, multifunctional nanocarriers, for cancer theranostics, is demonstrated here.
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Shouyan
S
Wang
Gwangseong
G
Kim
Yong-Eun Koo
YE
Lee
Hoe Jin
HJ
Hah
Manivannan
M
Ethirajan
Ravindra K
RK
Pandey
Raoul
R
Kopelman
D020341:Absorbable Implants; D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D000099166:Polyacrylamides
D000180:Acrylic Resins; D005456:Fluorescent Dyes; D053769:Nanocapsules; D017319:Photosensitizing Agents; D000099166:Polyacrylamides