Visible drug delivery by supramolecular nanocarriers directing to single-platformed diagnosis and therapy of pancreatic tumor model.
Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)-based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r(1) of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential.
Kaida
Sachiko
S
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, Department of Materials Engineering, Graduate School of Engineering, and Center for NanoBio Integration, The University of Tokyo, Tokyo, Japan.
Cabral
Horacio
H
Kumagai
Michiaki
M
Kishimura
Akihiro
A
Terada
Yasuko
Y
Sekino
Masaki
M
Aoki
Ichio
I
Nishiyama
Nobuhiro
N
Tani
Toru
T
Kataoka
Kazunori
K
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
D008823:Micelles; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C013933:dichloro-1,2-diaminocyclohexane platinum complex; D019786:Gadolinium DTPA