Institute for Cancer Research, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.
BMB Rep. 2010 Dec;43(12):781-8. doi: 10.5483/BMBRep.2010.43.12.781.
An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.
在腺病毒（Ad）介导的癌症基因治疗领域，一个经常被忽视的问题是其有效全身递送的能力有限。虽然通过瘤内注射传统 Ad 载体可以有效地治疗原发性肿瘤，但全身转移很难治愈。全身给予传统的裸 Ad 会导致 Ad 颗粒在肝脏中急性聚集，诱导中和抗体产生，血液循环半衰期短，在非预期的器官中无特异性分布，以及在目标疾病部位的选择性积累低。设计了各种涉及用聚合物和纳米材料修饰病毒表面的多功能策略，旨在通过全身给药最大限度地提高 Ad 的抗肿瘤活性和特异性。病毒和非病毒纳米材料的整合将极大地推动这两个领域的发展，为基因治疗创造新的概念。本综述重点介绍了基于各种设计策略的智能 Ad 杂化纳米复合物的最新进展，以实现 Ad 的最佳全身给药。
