Poly (γ, L-glutamic acid)-cisplatin bioconjugate exhibits potent antitumor activity with low toxicity: a comparative study with clinically used platinum derivatives.
We have recently synthesized a new platinum derivative, poly (γ, L-glutamic acid)-cisplatin conjugate (γ-PGA-CDDP), and shown that it displayed remarkable antitumor activity against breast tumor in a mouse model. The purpose of this study is to systematically compare this new drug with three platinum derivatives currently used in the clinic: cisplatin, carboplatin and oxaliplatin. Here, we show that γ-PGA-CDDP displays impressive antitumor activity over the current clinically used platinum drugs. More interestingly and more importantly, γ-PGA-CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative stress and improves antioxidative capability in vivo. Animals treated with γ-PGA-CDDP display the same profile of body weight as the control animals, while the tumors in γ-PGA-CDDP-treated animals are significantly suppressed compared with those treated with carboplatin and oxaliplatin. Our data suggest that γ-PGA could be used as an effective carrier for drug delivery and that γ-PGA-CDDP conjugate may have potential therapeutic applications in human cancers that are sensitive to treatment with CDDP-based chemotherapy such as ovarian cancer.
Feng
Zhen
Z
Molecular Biology Laboratory, School of Life Science, East China Normal University, Shanghai, China.
Lai
Yuping
Y
Ye
Haifeng
H
Huang
Jing
J
Xi
Xu Guang
XG
Wu
Zirong
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D016190:Carboplatin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C511775:poly(gamma-glutamic acid); D000077150:Oxaliplatin; D011099:Polyglutamic Acid; D016190:Carboplatin; D002945:Cisplatin
Biomaterials. 2010 Jul;31(20):5397-407
20398933
Neurotoxicology. 2008 Nov;29(6):1100-6
18845186
Biomaterials. 2006 Dec;27(35):5958-65
16949149
J Natl Cancer Inst. 2006 Mar 1;98(5):335-44
16507830
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4607-12
9539785
J Chromatogr B Biomed Appl. 1995 Jan 6;663(1):181-6
7704209
Expert Rev Anticancer Ther. 2008 Aug;8(8):1223-36
18699761
Cancer Treat Rev. 2008 Jun;34(4):368-77
18281158
J Pharm Biomed Anal. 1995 Aug;13(9):1173-8
8573645
Toxicology. 2008 Dec 5;254(1-2):51-60
18852009
J Nanosci Nanotechnol. 2009 Dec;9(12):7130-5
19908743
Oncol Rep. 2003 Nov-Dec;10(6):1663-82
14534679
Lung Cancer. 2010 Feb;67(2):194-7
19409644
Jpn J Cancer Res. 1998 Mar;89(3):307-14
9600125
Hear Res. 2009 Sep;255(1-2):33-43
19435600
Mol Cancer Ther. 2009 Jan;8(1):10-6
19139108
Lung Cancer. 2009 Jun;64(3):319-25
19095327
J Control Release. 1998 Apr 30;53(1-3):49-67
9741913
J Pharm Sci. 2009 Nov;98(11):3879-85
19340883