Huang Wenwen, Rollett Alexandra, Kaplan David L
Tufts University, Department of Biomedical Engineering , 4 Colby Street, Medford, MA 02155 , USA.
Expert Opin Drug Deliv. 2015 May;12(5):779-91. doi: 10.1517/17425247.2015.989830. Epub 2014 Dec 5.
Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release.
An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications.
The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.
基因工程生物材料因其合理的设计、可调节的结构功能、生物相容性、可降解性和靶向特异性,在控制释放方面具有重要作用。丝弹性蛋白样蛋白(SELPs)是一类基因工程重组蛋白聚合物,具备这些特性。此外,鉴于半结晶丝段和弹性体弹性蛋白段相结合的优势,SELP具有多刺激响应特性和可调节性,因此成为靶向癌症治疗递送和基因控制释放的有潜力候选者。
本文提供了用于药物递送和基因释放的SELP生物材料概述。讨论了用于SELP生产的生物合成策略、基本物理化学性质和自组装机制。综述重点关注序列-结构-功能关系、刺激响应特性以及当前和潜在的药物递送应用。
可调节的材料特性使SELP有望成为纳米载体和可注射药物释放系统的生物材料。目前SELP的应用主要集中在基于肿瘤或感染部位局部热疗的热触发生物材料形式的治疗递送。SELP作为用于基因释放的可注射水凝胶的其他突出控释应用也在探索中。利用其他刺激(包括pH值、离子强度、氧化还原、酶刺激和电场)来触发SELP的可逆材料响应以实现靶向递送的进一步生物医学应用正在进行中。利用这些额外的刺激响应特性将为控制治疗释放和组织再生提供更广泛的功能性生物材料。