Superior antimetastatic effect of pemetrexed-loaded gelatinase-responsive nanoparticles in a mouse metastasis model.
Novel pemetrexed-loaded gelatinase-responsive nanoparticles were prepared as a targeted delivery system to determine its potential for clinical therapy of malignant melanoma. The pemetrexed-loaded poly(ethylene glycol)(PEG)-peptide-poly(ε-caprolactone) (PCL) nanoparticles included a gelatinase-cleavage peptide and a PEG-PCL-based structure. The pemetrexed-loaded PEG-peptide-PCL nanoparticles have shown the best antimetastatic effect in experimental lung metastasis models. The expressions of CD133 and thymidylate synthetase of metastatic tumors were also evaluated in our studies. Our results showed that pemetrexed-loaded gelatinase-responsive nanoparticles may represent a potent drug delivery system for inhibiting pulmonary metastasis and our preclinical results can provide new avenues for clinical therapy of malignant melanoma.
The Comprehensive Cancer Center of Drum Tower Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China.
Nannan
N
Lu
Qin
Q
Liu
Rutian
R
Li
Li
L
Xie
Jie
J
Shen
Wenxian
W
Guan
Xiaoping
X
Qian
Lixia
L
Yu
Yitao
Y
Ding
Xiqun
X
Jiang
Baorui
B
Liu
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D018093:Gelatinases / Q000378:metabolism*; D005971:Glutamates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006023:Glycoproteins / Q000378:metabolism; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009362:Neoplasm Metastasis; D000068437:Pemetrexed; D010455:Peptides / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D013940:Thymidylate Synthase / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D005971:Glutamates; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse; D000068437:Pemetrexed; D011092:Polyethylene Glycols; D006147:Guanine; D013940:Thymidylate Synthase; D018093:Gelatinases