title: In vitro and in vivo targeted delivery of photosensitizers to the tumor cells for enhanced photodynamic effects.
abstract: BACKGROUND
  Efficacy of photodynamic therapy can be enhanced by improving uptake, localization, and sub-cellular localization of sensitizers at the sensitive targets.
  
  
  METHODS
  Uptake, localization, and photodynamic effects of hematoporphyrin derivative (HpD, Photosan-3; PS-3) and disulfonated aluminum phthalocyanine (AlPcS₂) were studied either encapsulated in liposomes or conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) in a brain glioma cell line, BMG-1.
  
  
  RESULTS
  Although the total uptake with encapsulated or conjugated sensitizers was less than the free sensitizers, photodynamic efficiency was higher due to the localization of the sensitizer at the sensitive targets. Biodistribution of intravenously administered technetium (⁹⁹m Tc)-labeled PS-3 analyzed by gamma camera imaging showed maximum accumulation in the liver followed by tumor. Tumor/muscle (T/N) ratio of free PS-3 was higher compared to encapsulated or conjugated PS-3 but the accumulation of PS-3 significantly reduced in brain and cutaneous tissue following modulated delivery. Pharmacokinetics suggested faster accumulation of encapsulated and conjugated PS-3 in the tumor.
  
  
  CONCLUSIONS
  Localization of sensitizers at sensitive targets and reduced accumulation in normal tissues with liposome encapsulation and antibody conjugation suggest that these two delivery systems can potentially enhance the efficacy of photodynamic treatment.
authors: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig S K Mazumdar Road, Delhi, India. sgupta3@med.miami.edu
authors: Seema
authors: S
authors: Gupta
authors: Bilikere S
authors: BS
authors: Dwarakanath
authors: N K
authors: NK
authors: Chaudhury
authors: Anil K
authors: AK
authors: Mishra
authors: K
authors: K
authors: Muralidhar
authors: Viney
authors: V
authors: Jain
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D006415:Hematoporphyrins; D007211:Indoles; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C071875:photosan III; C064331:aluminum phthalocyanine disulfonate