Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 11529, Taiwan, ROC.
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 40201, Taiwan, ROC.
J Nanobiotechnology. 2019 Feb 6;17(1):25. doi: 10.1186/s12951-019-0457-3.
A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h.
Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model.
LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.
阳离子脂质体-PEG-PEI 复合物（LPPC）被用作载体，实现药物对人表皮生长因子受体-2（HER2/neu）表达的乳腺癌细胞的靶向递送。LPPC 可以很容易地装载抗肿瘤药物，并与临床上用于在 1 小时内快速形成免疫颗粒的抗肿瘤抗体如赫赛汀等非共价结合。
载药 LPPC 的平均粒径约为 250nm，zeta 电位约为 40mV。赫赛汀被复合到 LPPC 的表面，形成药物/LPPC/赫赛汀复合物。姜黄素/LPPC/赫赛汀复合物的粒径为 280nm，zeta 电位约为 23mV。通过在细胞表面的特异性结合和体内 IVIS 图像，证明了该递药系统的靶向能力，与 HER2 阴性 Hs578T 细胞相比，该递药系统在 HER2 阳性 SKBR3 细胞上显示出特异性结合。只有药物/LPPC/赫赛汀复合物在癌细胞中表现出显著增加的细胞毒性活性。体内外结果均表明，吸附在 LPPC 上的赫赛汀将免疫复合物导向 HER2/neu 阳性细胞，而不是 HER2/neu 阴性细胞。与单独使用药物和其他治疗组（包括临床剂量的赫赛汀和 LipoDox）相比，LPPC 递送系统中使用的任何一种药物（姜黄素或阿霉素）的复合物在异种移植模型中均提供了更好的治疗效果。
LPPC 通过为用于乳腺癌治疗的药物很容易地引入特定的靶向特性，显示出重要的临床意义。
