TAT-modified nanosilver for combating multidrug-resistant cancer.
A nanopharmaceutical system using TAT-enhanced cell/tissue penetration strategy was developed for multidrug-resistant (MDR) cancer treatment, in which nanocrystalline silver with mean size of 8 nm modified with TAT cell-penetrating peptide (termed AgNP-TAT) displayed extraordinary antitumor activity in both MDR cells and non-resistant cells at an indiscriminating manner. Such anti-MDR effect is presumably due to the size-exclusion effect, by which the nanoparticles are too large to be pumped out. Of note, AgNP-TAT showed significant enhancement in killing tumor cells, e.g. up to 24 fold higher compared to its counterpart without TAT-modification. The animal studies further confirmed the success of our strategy that AgNP-TAT was able to effectively inhibit the tumor growth in the mice bearing malignant melanoma at a dose of 1 nmol/kg, compared with the effective dose (4.3 μmol/kg) of doxorubicin. AgNP-TAT also showed significantly reduced adverse toxicity in vivo. It indicates AgNP-TAT could be a class of nano drug for MDR cancer treatment.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
Jinhua
J
Liu
Yongxing
Y
Zhao
Qianqian
Q
Guo
Zhao
Z
Wang
Huiyuan
H
Wang
Yongxin
Y
Yang
Yongzhuo
Y
Huang
D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D012834:Silver / Q000737:chemistry*
D057846:Cell-Penetrating Peptides; D012834:Silver