Reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles for doxorubicin delivery.
We report a reducible copolymer self-assembled with superparamagnetic iron oxide nanoparticles (SPIONs) to deliver doxorubicin (DOX) for cancer therapy. The copolymer of reducible polyamidoamine (rPAA) with poly(ethylene glycol)(PEG)/dodecyl amine graft was synthesized by Michael addition. rPAA@SPIONs were formed by the alkyl grafts of reducible copolymers intercalated with the oleic acid layer capped on the surface of magnetite nanocrystals. The intercalating area formed a reservoir for hydrophobic anti-cancer drug (DOX), whilst the PEG moiety in the copolymers helped the nanoparticle well-dispersible in aqueous solution. We employed two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman (CARS) to investigate drug delivery in intra-cellular structures of live cells, and used Vivaview(®) technique to show real-time inhibition efficacy of nanoparticles in live cells. rPAA@SPIONs present efficiently drug loading with reducible responsibility in vitro tests. Finally, rPAA@SPIONs were tested in mice with xenograft MDA-MB-231 breast tumor though i.v. injection and inhibited tumor growth efficiently. MRI was used to monitor nanoparticles aggregation in tumor site. Histology and Prussian blue on kidney, liver, and heart in mice indicated that DOX/rPAA@SPIONs showed no significant toxicity for mice organs after 24 days treatment.
School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China; Department of Mechanical Engineering, University of Manitoba, Winnipeg MB R3T 2N2, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg MB R3T 2N2, Canada; Manitoba Institute of Child Health, Canada; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
Jun
J
Chen
Min
M
Shi
Pengmin
P
Liu
Alex
A
Ko
Wen
W
Zhong
WangJun
W
Liao
Malcolm M Q
MM
Xing
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010084:Oxidation-Reduction; D011073:Polyamines / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; C531249:Poly(amidoamine); D011073:Polyamines; D004317:Doxorubicin
Breast tumor; Magnetic nanoparticle; Reducible polymer; Self-assembly; Theranostics