EXTRAVASATION AND TRANSCYTOSIS OF LIPOSOMES IN KAPOSI SARCOMA-LIKE DERMAL LESIONS OF TRANSGENIC MICE BEARING THE HIV TAT GENE

Transgenic mice bearing the HIV tat gene develop dermal lesions resemb ling a common malignant tumor in AIDS, Kaposi's sarcoma (KS). To evalu ate the permeability characteristics of these lesions and the therapeu tic potential of drug-carrying liposomes, we have studied the localiza tion of sterically stabilized liposomes, which show long circulation t ime in blood and increased accumulation in tumors. Liposomes encapsula ting colloidal gold were injected intravenously into transgenic mice b earing KS lesions, and tissues were processed 24 hours later for both electron microscopy and for light microscopy with silver enhancement. Liposomes and silver marker were detected predominantly in the dermis surrounding the early and mature KS lesions, which were characterized by a proliferation of fibroblast-like spindle cells and abnormal blood vessels close to the epidermis. The silver-enhanced gold marker often surrounded vascular channels and scattered erythrocytes. As determine d by electron microscopy, some spindle cells and macrophages had inges ted intact liposomes. Transendothelial transport of liposomes was obse rved both through open channels between endothelial cells and also thr ough endothelial cells lining intact vessels. Both extravasation and t ranscytosis of liposomes through irregular endothelium were much highe r in KS lesions than in the adjacent normal skin. The high accumulatio n of sterically stabilized liposomes in KS lesions and their intracell ular uptake by some spindle cells enhances their potential as carriers of chemotherapeutic agents against this neoplasm.