Sacks P G, Oke V, Mehta K
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J Cancer Res Clin Oncol. 1992;118(7):490-6. doi: 10.1007/BF01225262.
Antiproliferative effects of free retinoic acid (RA) and liposome-encapsulated RA (RAlp) were compared in a squamous carcinoma system using both monolayer cells and multicellular tumor spheroids (MTS), an in-vivo-like model with three-dimensional histological structure. Initial studies examined the effect of lipid composition on the efficiency of RA encapsulation and on the subsequent toxicity of RAlp to red blood cells. In 5-day growth assays for monolayer cells, RA and RAlp (1 microM-0.1 nM) produced similar growth inhibition. In 6-day growth assays for MTS, RAlp was shown to have increased effectiveness. Liposomal uptake by the squamous carcinoma cells was examined by culturing monolayers and MTS with fluorescence-tagged liposomes and examining them under fluorescence microscopy between days 1 and 6. Phagocytosed liposomes were present, but their low levels suggested that other mechanisms of drug delivery such as adsorption, fusion or direct lipid transfer probably occurred for RAlp. Histological examination of MTS showed that RA and RAlp produced similar alterations. In this squamous carcinoma system, liposomes are effective in delivering retinoic acid and in producing biological effects in monolayer cells and within the three-dimensional structure of MTS.
在一个鳞状细胞癌系统中，使用单层细胞和多细胞肿瘤球体（MTS，一种具有三维组织结构的类体内模型）比较了游离视黄酸（RA）和脂质体包裹的RA（RAlp）的抗增殖作用。初步研究考察了脂质组成对RA包封效率以及RAlp随后对红细胞毒性的影响。在单层细胞的5天生长试验中，RA和RAlp（1微摩尔 - 0.1纳摩尔）产生了相似的生长抑制作用。在MTS的6天生长试验中，RAlp显示出更高的有效性。通过用荧光标记的脂质体培养单层细胞和MTS，并在第1天至第6天期间在荧光显微镜下检查，研究了鳞状癌细胞对脂质体的摄取情况。存在吞噬的脂质体，但其含量较低，这表明RAlp可能通过其他药物递送机制发挥作用，如吸附、融合或直接脂质转移。MTS的组织学检查表明，RA和RAlp产生了相似的改变。在这个鳞状细胞癌系统中，脂质体能够有效地递送视黄酸，并在单层细胞以及MTS的三维结构中产生生物学效应。
