Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine.
Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine.
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DOI：
10.1021/jacsau.1c00313
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发表时间：
2022-01-24
期刊：
影响因子：
8
通讯作者：
Hammond PT
中科院分区：
文献类型：
--
作者：
Boehnke N;Hammond PT
纳米载体具有通过靶向给药来推进个性化药物治疗的巨大潜力。然而，到目前为止，由于对纳米生物相互作用的不完全理解，改善目标疾病部位纳米颗粒积累的努力在很大程度上未能转化为临床应用。虽然在评估特定的物理和化学纳米颗粒特性对运输和摄取的影响方面取得了进展，但通过单独和联合控制这些特性以确定它们与不同类型细胞的相互作用将获得许多好处。我们和其他人最近开始利用基于库的纳米颗粒筛选来研究基于脂质和聚合物的药物输送系统的结构-功能关系，以指导纳米颗粒的设计。这些组合筛选工作在成功识别关键特征方面显示出希望，这些关键特征在目标部位产生改进和特定的积累。然而，同样需要考虑生物复杂性对纳米颗粒传递的影响，特别是在临床翻译的背景下。例如，组织和细胞的异质性为纳米颗粒的运输、摄取和积累提供了一个额外的维度；应用成像和筛选工具以及生物信息学可能进一步扩大我们对纳米颗粒如何与细胞和组织接触的理解。鉴于组学和机器学习领域的最新进展，通过使用集成屏幕，利用纳米粒子库和临床注释生物数据集提供的组合参数空间，并结合高通量的活体研究，有很大的希望改变纳米载体的开发。
Nanocarriers have significant potential to advance personalized medicine through targeted drug delivery. However, to date, efforts to improve nanoparticle accumulation at target disease sites have largely failed to translate clinically, stemming from an incomplete understanding of nano–bio interactions. While progress has been made to evaluate the effects of specific physical and chemical nanoparticle properties on trafficking and uptake, there is much to be gained from controlling these properties singularly and in combination to determine their interactions with different cell types. We and others have recently begun leveraging library-based nanoparticle screens to study structure–function relationships of lipid- and polymer-based drug delivery systems to guide nanoparticle design. These combinatorial screening efforts are showing promise in leading to the successful identification of critical characteristics that yield improved and specific accumulation at target sites. However, there is a crucial need to equally consider the influence of biological complexity on nanoparticle delivery, particularly in the context of clinical translation. For example, tissue and cellular heterogeneity presents an additional dimension to nanoparticle trafficking, uptake, and accumulation; applying imaging and screening tools as well as bioinformatics may further expand our understanding of how nanoparticles engage with cells and tissues. Given recent advances in the fields of omics and machine learning, there is substantial promise to revolutionize nanocarrier development through the use of integrated screens, harnessing the combinatorial parameter space afforded both by nanoparticle libraries and clinically annotated biological data sets in combination with high throughput in vivo studies.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
22.7
作者：
Corsello, Steven M.;Nagari, Rohith T.;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
15
作者：
Chen, Delai;Love, Kevin T.;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
17.1
作者：
Barberio AE;Smith SG;Correa S;Nguyen C;Nhan B;Melo M;Tokatlian T;Suh H;Irvine DJ;Hammond PT
通讯作者：
Hammond PT