Delivery of intracellular-acting biologics in pro-apoptotic therapies.
Delivery of intracellular-acting biologics in pro-apoptotic therapies.
复制标题
DOI：
10.2174/138161211795049642
复制
发表时间：
2011
影响因子：
3.1
通讯作者：
Duvall CL
中科院分区：
文献类型：
--
作者：
Li H;Nelson CE;Evans BC;Duvall CL
The recent elucidation of molecular regulators of apoptosis and their roles in cellular oncogenesis has motivated the development of biomacromolecular anticancer therapeutics that can activate intracellular apoptotic signaling pathways. Pharmaceutical scientists have employed a variety of classes of biologics toward this goal, including antisense oligodeoxynucleotides, small interfering RNA, proteins, antibodies, and peptides. However, stability in the in vivo environment, tumor-specific biodistribution, cell internalization, and localization to the intracellular microenvironment where the targeted molecule is localized pose significant challenges that limit the ability to directly apply intracellular-acting, pro-apoptotic biologics for therapeutic use. Thus, approaches to improve the pharmaceutical properties of therapeutic biomacromolecules are of great significance and have included chemically modifying the bioactive molecule itself or formulation with auxiliary compounds. Recently, promising advances in delivery of pro-apoptotic biomacromolecular agents have been made using tools such as peptide “stapling”, cell penetrating peptides, fusogenic peptides, liposomes, nanoparticles, smart polymers, and synergistic combinations of these components. This review will discuss the molecular mediators of cellular apoptosis, the respective mechanisms by which these mediators are dysregulated in cellular oncogenesis, the history and development of both nucleic-acid and amino-acid based drugs, and techniques to achieve intracellular delivery of these biologics. Finally, recent applications where pro-apoptotic functionality has been achieved through delivery of intracellular-acting biomacromolecular drugs will be highlighted.
登录
查看更多内容
DOI：
10.1042/bj20100814
发表时间：
2010-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Altieri DC
通讯作者：
Altieri DC
影响因子：
--
作者：
Aigner, Achim
通讯作者：
Aigner, Achim
影响因子：
4.1
作者：
Aigner, A
通讯作者：
Aigner, A
影响因子：
17.3
作者：
Banga, AK;Prausnitz, MR
通讯作者：
Prausnitz, MR
影响因子：
45.3
作者：
Bedikian, Agop Y.;Millward, Michael;Haluska, Frank G.
通讯作者：
Haluska, Frank G.