Antitumor efficacy of colon-specific HPMA copolymer/9-aminocamptothecin conjugates in mice bearing human-colon carcinoma xenografts.
The antitumor activity of a colon-specific N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - 9-aminocamptothecin (9-AC) conjugate (P-9-AC) was assessed in orthotopic and subcutaneous animal (HT29 xenograft) tumor models. P-9-AC treatment of mice bearing orthotopic colon tumors, with a dose of 3 mg/kg of 9-AC equivalent every other day for 6 weeks, resulted in regression of tumors in 9 of 10 mice. A lower dose of P-9-AC (1.25 mg/kg of 9-AC equivalent) every other day for 8 weeks inhibited subcutaneous tumor growth in all mice. No liver metastases were observed. Colon-specific release of 9-AC from polymer conjugates enhanced antitumor activity and minimized the systemic toxicity.
Gao
Song-Qi
SQ
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
Sun
Yongen
Y
Kopecková
Pavla
P
Peterson
C Matthew
CM
Kopecek
Jindrich
J
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008689:Methacrylates; D011108:Polymers; C080125:9-aminocamptothecin; C032802:hydroxypropyl methacrylate; D002166:Camptothecin
Br J Cancer. 2006 Jun 19;94(12):1898-905
16755300
Cancer Res. 2004 Jul 15;64(14):4931-41
15256466
J Clin Oncol. 1996 Apr;14(4):1236-44
8648379
J Control Release. 2001 Aug 10;75(3):365-79
11489323
Int J Cancer. 2002 Sep 1;101(1):23-31
12209584
Cancer Res. 1992 Apr 1;52(7):1823-9
1312900
Cancer Chemother Pharmacol. 2003 Oct;52(4):333-8
12819941
J Control Release. 2006 Jan 10;110(2):323-331
16290118
Pharm Res. 2008 Jan;25(1):218-26
17929146
Clin Cancer Res. 2002 Mar;8(3):641-61
11895891
Int J Cancer. 1994 Dec 1;59(5):607-11
7960233
Cancer Res. 1995 May 15;55(10):2116-21
7743511
Clin Cancer Res. 2001 Feb;7(2):229-30
11234873
Int J Cancer. 2007 Feb 1;120(3):585-93
17096339
Dis Colon Rectum. 2005 Dec;48(12):2197-208
16400510
Cancer. 1999 Feb 15;85(4):786-95
10091755
Tumour Biol. 2003 Jan-Feb;24(1):32-9
12743424
J Clin Gastroenterol. 2006 Aug;40(7):592-5
16917399
Cancer Res. 1989 Aug 15;49(16):4385-9
2545341
Science. 1989 Nov 24;246(4933):1046-8
2555920
Jpn J Cancer Res. 1990 Jan;81(1):58-62
2108947
Cancer Res. 1990 Nov 1;50(21):6919-24
1698546
Invest New Drugs. 2004 Aug;22(3):323-7
15122080
Cancer Res. 1989 Sep 15;49(18):5016-22
2548707
Science. 1998 Mar 6;279(5356):1534-41
9488652
Clin Cancer Res. 2003 Jun;9(6):2066-71
12796369
J Clin Oncol. 1998 Jul;16(7):2345-51
9667249
Cancer Res. 1989 Sep 15;49(18):5077-82
2548710
J Clin Oncol. 1999 Jul;17(7):2219-26
10561279
Drugs. 2002;62(14):2039-57
12269849
J Control Release. 2007 Feb 12;117(2):179-85
17150276
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4955-60
17360326
Clin Cancer Res. 1995 Mar;1(3):269-76
9815982
Cell. 1990 Aug 10;62(3):403-6
2165864
Cancer Res. 1998 Mar 1;58(5):976-84
9500459
Ann Oncol. 1998 Oct;9(10):1085-90
9834820
Br J Cancer. 2006 Oct 9;95(7):906-13
16983402
Cancer Chemother Pharmacol. 2009 Apr;63(5):793-8
18648813
Int J Cancer. 2008 May 15;122(10):2223-32
18214853
Clin Cancer Res. 2003 Apr;9(4):1546-56
12684431
Bioconjug Chem. 2000 Jan-Feb;11(1):3-7
10639078
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7024-7
2823250
Cancer Res. 1993 Jul 1;53(13):3062-9
8319213
Cell. 1988 May 6;53(3):433-40
2835168
J Clin Oncol. 1997 Jan;15(1):251-60
8996150
Clin Cancer Res. 2004 Mar 15;10(6):2158-67
15041737