In vitro and in vivo targeted delivery of photosensitizers to the tumor cells for enhanced photodynamic effects

• Published in: Journal of cancer research and therapeutics 2011-07, Vol.7 (3), p.314-324
• Main Authors: Gupta, Seema, Dwarakanath, Bilikere S, Chaudhury, N K, Mishra, Anil K, Muralidhar, K, Jain, Viney
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Cancer; Carcinoembryonic Antigen - immunology; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - metabolism; Care and treatment; Cell Line, Tumor; Drug Delivery Systems; Gliomas; Health aspects; Hematoporphyrins - administration & dosage; Hematoporphyrins - pharmacokinetics; Hematoporphyrins - pharmacology; Indoles - administration & dosage; Indoles - pharmacokinetics; Indoles - pharmacology; Liposomes; Liver - metabolism; Male; Mice; Organometallic Compounds - administration & dosage; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - pharmacology; Pharmacokinetics; Photochemotherapy; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacokinetics; Tissue Distribution; Tumors
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/0973-1482.87035

Efficacy of photodynamic therapy can be enhanced by improving uptake, localization, and sub-cellular localization of sensitizers at the sensitive targets. 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. 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. 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.