Targeting Ligand Core One major challenge in cancer nanotechnology is how to selectively deliver funcfional nanoparticles to cancer cells. The overall thrust of the Targefing Ligand Core is to provide novel targeting ligands that can be used to direct nanoparticles to particular cancer cell types for projects 1, 2 and 3. Two powerful combinatorial library technologies will be used to generate the desired targefing ligands, including single domain antibodies (SDAs), single domain antibody mimics (SDAMs), and 2'-F/2'-OMe RNA aptamers. The use of two different technologies for protein-based and nudeic acid-based biomolecules, respectively, will ensure that the desired targefing ligands will be rapidly identified and made available to the Projects. Specifically, we will create monomeric (milestone 1) and multimeric (milestone 2) SDAs and SDAMS with high affinity and specificity for EGFR, mesothelin, and other promising cancer biomarkers. We will also use a combinafion of cell-SELEX and conventional SELEX to generate 2'-F and 2'-OMe RNA aptamers that can specifically bind to EGFR or mesothelin expressing lung cancer cells (milestone 3). The resulting targeting ligands will incorporate functional groups such as Cys or Lys at site(s) away from the target-binding region, to facilitate site-specific conjugafion with various nanoparticles that are used in Projects 1, 2, and 3.

Public Health Relevance

Targeted therapy has the potential of reducing toxicity of chemotherapy for cancer management. Nanoparticles targeted to primary and metastatic cancer may improve the standard of care and quality of life for cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA151652-02
Application #
8309350
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$79,459
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Sun, Junjiang; Shao, Wenwei; Chen, Xiaojing et al. (2018) An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs. Mol Ther Methods Clin Dev 10:257-267
Liu, Lina; Wang, Yuhua; Miao, Lei et al. (2018) Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer. Mol Ther 26:45-55
Starling, Brittney R; Kumar, Parag; Lucas, Andrew T et al. (2018) Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients. Cancer Chemother Pharmacol :
Chai, Zheng; Zhang, Xintao; Rigsbee, Kelly Michelle et al. (2018) Cryoprecipitate augments the global transduction of the adeno-associated virus serotype 9 after a systemic administration. J Control Release 286:415-424
Wang, Yuhua; Zhang, Lu; Xu, Zhenghong et al. (2018) mRNA Vaccine with Antigen-Specific Checkpoint Blockade Induces an Enhanced Immune Response against Established Melanoma. Mol Ther 26:420-434
Pei, Xiaolei; He, Ting; Hall, Nikita E et al. (2018) AAV8 virions hijack serum proteins to increase hepatocyte binding for transduction enhancement. Virology 518:95-102
Zhang, Xintao; He, Ting; Chai, Zheng et al. (2018) Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration. Biomaterials 176:71-83
Lucas, Andrew T; White, Taylor F; Deal, Allison M et al. (2017) Profiling the relationship between tumor-associated macrophages and pharmacokinetics of liposomal agents in preclinical murine models. Nanomedicine 13:471-482
Kim, Junghyun; Luo, Zhi-Xiang; Wu, Yue et al. (2017) In-Situ Formation of Holmium Oxide in Pores of Mesoporous Carbon Nanoparticles as Substrates for Neutron-Activatable Radiotherapeutics. Carbon N Y 117:92-99
Huo, Meirong; Zhao, Yan; Satterlee, Andrew Benson et al. (2017) Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced melanoma by remodeling the tumor microenvironment. J Control Release 245:81-94

Showing the most recent 10 out of 190 publications