权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Reagents for the Design of Targeted Multifunctional Nanomaterials

用于设计靶向多功能纳米材料的试剂

基本信息

批准号：
7880082
负责人：
LEE JOSEPHSON
金额：
$ 39.43万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880082
关键词：
Animals Antibodies Binding Bombesin Cells Charge Chelating Agents Chemistry Clinic Clinical Cultured Cells Detection Development Diagnostic Drug Delivery Systems Esters Fluorochrome GRP gene Glioma Goals Haptens Image Immunohistochemistry Kidney Kinetics Lead Liver Magnetism Maleimides Malignant neoplasm of prostate Methods Modality Modeling Organ Penetration Peptides Polymers Property Prostate Proteins Reaction Reagent Reporter Research Solutions Spatial Distribution Structure Therapeutic Tissues Translations Xenograft Model anti-CEA scFv base biological systems bombesin like peptide cancer cell chemical property chromophore colon cancer cell line design functional group hydrophilicity imaging modality improved nanomaterials nanoparticle neoplastic cell next generation physical property public health relevance receptor scaffold single photon emission computed tomography stoichiometry tumor uptake

项目摘要

DESCRIPTION (provided by applicant): The need to maximize tumor uptake, and minimize uptake by other organs, is a common and formidable hurdle for many drug delivery and imaging applications. To attain this goal, new chemistries are required that attach multiple functional groups to substrates (substrates = nanoparticles, proteins, peptides), so a single probe's fate in biological systems can be easily detected by the different modalities needed to ascertain probe disposition at the cellular, tissue and whole animal levels. In addition, these chemistries need to simultaneously alter the physical properties of the probe (e.g., hydrophilicity, charge), to maximize tumor targeting. Finally, it is essential that these new chemistries provide probes with the rigorously defined chemical properties needed for the clinical translation. A solution to these three problems in multifunctional materials design lies in a new class of reagents termed Multifunctional Single Attachment Point or MSAP's. MSAP's consist of a short peptide scaffolds to which multiple functional groups and a single reactive group, such an NHS ester or maleimide, are attached. The RG of the MSAP then attaches the MSAP (and its multiple functional groups) to a substrate in a single reaction, to yield a multifunctional probe. (Note: MSAP reagent + substrate = multifunctional probe). The functional groups employed in an MSAP reagent (i) permit the disposition of the resulting probe to be determined in biological systems (functional groups can be chromophores, fluorochromes, chelating groups or immunoreactive haptens) and, (ii) permit the physical properties of the resulting probe to be controlled and optimized (functional groups = hydrophilic polymers or a small charged structures). Multifiunctional MSAP based probes achieve a stoichiometry between multiple functional groups based on the MSAP reagent, a feature essential for the eventual clinical use of multifunctional materials. We shall expand MSAP chemistry by synthesizing MSAP reagent panels and demonstrate their broad applicability with three different types of substrates: (i) a NP substrate, obtaining enhanced glioma targeting), (ii) an anti-CEA scFv antibody substrate (enhanced tumor CEA targeting) and, (iii) a bombesin (BN) peptide substrate (enhanced tumor GRP receptor targeting). PUBLIC HEALTH RELEVANCE: Our goal is the development of a new type of reagent for designing multifunctional nanomaterials that will enable materials to be detected by different imaging modalities and which will enable them to target tumors more effectively.