MacDiarmid Jennifer A, Mugridge Nancy B, Weiss Jocelyn C, Phillips Leo, Burn Adam L, Paulin Richard P, Haasdyk Joel E, Dickson Kristie-Ann, Brahmbhatt Vatsala N, Pattison Scott T, James Alexander C, Al Bakri Ghalib, Straw Rodney C, Stillman Bruce, Graham Robert M, Brahmbhatt Himanshu
EnGeneIC Pty Ltd., 105 Delhi Road, North Ryde, Sydney, NSW 2113, Australia.
Cancer Cell. 2007 May;11(5):431-45. doi: 10.1016/j.ccr.2007.03.012.
Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.
全身给药化疗药物会导致药物无差别分布和严重毒性。在此，我们报告一种技术，该技术可能通过将化疗药物封装在细菌衍生的400纳米微细胞中并使其靶向癌细胞，从而克服这些缺点。我们发现，微细胞可以包装有治疗浓度显著的不同电荷、疏水性和溶解性的化疗药物。通过双特异性抗体靶向癌细胞膜上的受体，微细胞会发生内吞作用、细胞内降解并释放药物。这在小鼠异种移植瘤和犬淋巴瘤病例研究中产生了显著的肿瘤生长抑制和消退，尽管只给予了微量的药物和抗体；这是限制全身毒性的关键因素，应允许使用联合化疗的复杂方案。
