Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.
Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.
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纳米医学需要将生物相容性材料自组装成纳米级载药包装的新策略，以提高治疗效果。为了满足这一需求，我们开发了人工重组嵌合多肽（CP），其在与包括化疗药物在内的各种疏水分子缀合后自发自组装成小于100 nm大小的近单分散纳米颗粒。这些CP由连接到短的富含Cys的区段的可生物降解的多肽组成。Cys残基与疏水性小分子（包括化学治疗剂）的结构多样性集合的共价修饰导致在CP组成和分子量范围内自发形成纳米颗粒。当用于向小鼠癌症模型递送化疗剂时，CP纳米颗粒具有比游离药物高四倍的最大耐受剂量，并且在单次给药后诱导几乎完全的肿瘤消退。这种简单的策略可以促进药物、成像剂和靶向部分的共组装成多功能纳米药物。
New strategies to self-assemble biocompatible materials into nanoscale, drug-loaded packages with improved therapeutic efficacy are needed for nanomedicine. To address this need, we developed artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100 nm size, near monodisperse nanoparticles upon conjugation of diverse hydrophobic molecules, including chemotherapeutics. These CPs consist of a biodegradable polypeptide that is attached to a short Cys-rich segment. Covalent modification of the Cys residues with a structurally diverse set of hydrophobic small molecules, including chemotherapeutics leads to spontaneous formation of nanoparticles over a range of CP compositions and molecular weights. When used to deliver chemotherapeutics to a murine cancer model, CP nanoparticles have a four-fold higher maximum tolerated dose than free drug, and induce nearly complete tumor regression after a single dose. This simple strategy can promote co-assembly of drugs, imaging agents, and targeting moieties into multifunctional nanomedicines.
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DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.9
作者：
Batrakova, Elena V.;Kelly, David L.;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.
影响因子：
10.8
作者：
Furgeson, DY;Dreher, MR;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
10.8
作者：
Kabanov, AV;Batrakova, EV;Alakov, VY
通讯作者：
Alakov, VY
影响因子：
4.8
作者：
Drummond, JT;Anthoney, A;Modrich, P
通讯作者：
Modrich, P