title: PAMAM-camptothecin conjugate inhibits proliferation and induces nuclear fragmentation in colorectal carcinoma cells.
abstract: OBJECTIVE
  To synthesize and characterize a poly (amido amine) dendrimer-camptothecin (PAMAM-CPT) conjugate and evaluate its activity on human colorectal carcinoma cells (HCT-116).
  
  
  METHODS
  The attachment of CPT to amine-terminated PAMAM was facilitated through a succinic acid-glycine linker. The conjugate was characterized for absence of small molecular weight impurities, size and drug content. Stability of the conjugate in PBS and growth media and its in vitro activity on HCT-116 were studied. Cell cycle arrest and nuclear fragmentation upon PAMAM-CPT treatment were investigated.
  
  
  RESULTS
  The conjugate was stable under physiological pH (7.4) in PBS and in growth media (with 10% FBS) with minimal release of 4% and 6% drug, respectively, at 48 h. PAMAM-CPT inhibited proliferation of HCT-116 cells with an IC50 value of 1.6  ±  0.3 µM. The conjugate induced signs of cell cycle arrest with up to 68% of cells blocked in the G(2) phase. Confocal images of cells treated with PAMAM-CPT suggest nuclear fragmentation and formation of apoptotic bodies.
  
  
  CONCLUSIONS
  Results show that the PAMAM-CPT conjugate was active against colorectal cancer cells in vitro, inhibiting their growth and inducing nuclear fragmentation. Coupled with the ability to target macromolecular therapeutics to tumors, this conjugate shows promise for cancer chemotherapy.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah 84108, USA.
authors.forename: Giridhar
authors.initials: G
authors.lastname: Thiagarajan
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Alexander
authors.initials: A
authors.lastname: Malugin
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000737:chemistry* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003470:Culture Media; D050091:Dendrimers; C104700:PAMAM Starburst; D002166:Camptothecin