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Enhanced MRI‐Guided Gadolinium (III) Neutron Capture Therapy by Polymeric Nanocarriers Promoting Tumor Accumulation and Intracellular Delivery
Author(s) -
Qin Changyuan,
Hou Xuan,
Khan Thahomina,
Nitta Nobuhiro,
Yanagawa Masashi,
Sakurai Yuriko,
Suzuki Minoru,
Masunaga ShinIchiro,
Tanaka Hiroki,
Sakurai Yoshinori,
Takahashi Hiroyuki,
Aoki Ichio,
Yanagie Hironobu,
Cabral Horacio
Publication year - 2020
Publication title -
chemnanomat
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 32
ISSN - 2199-692X
DOI - 10.1002/cnma.201900730
Subject(s) - nanocarriers , gadolinium , dota , peg ratio , ethylene glycol , chelation , in vivo , chemistry , conjugated system , drug delivery , polymer , nuclear chemistry , materials science , organic chemistry , finance , microbiology and biotechnology , economics , biology
Gadolinium(III) (Gd(III)) chelates are promising compounds for developing MRI‐guided neutron capture therapies (NCT). However, despite their success as MRI contrast agents (CAs), current Gd(III) chelates do not present appropriate accumulation in tumors for effective NCT. To overcome this limitation, we developed a series of biocompatible polymeric nanocarriers conjugating Gd(III)‐chelates, i. e. Gd‐DOTA, as NCT agents with high MRI sensitivity and tumor delivery. These polymers were based on poly(aspartic acid) (P(Asp)) and were modified with poly(ethylene glycol) (PEG) chains having different molecular weight (M w ) for controlling stability and pharmacokinetics. The T 1 relaxivity of the Gd‐DOTA conjugated polymers increased 2‐fold compared to that of clinically used Gd(III) CAs. In vivo, the PEG‐modified polymers promoted the accumulation in tumor tissues, enhancing the MRI contrast of tumors. After neutron irradiation, the nanocarriers effectively suppressed the tumor growth, particularly the PEG‐P(Asp‐Gd‐DOTA) with shorter PEG chain, which promoted higher intracellular delivery, supporting their potential as NCT agents.