Current treatments for breast cancer focus on the killing malignant cells but there is a substantial population of patients for whom these approaches ultimately fail. The long-term objective of this work is to develop an adjuvant therapy that targets the tumor-promoting stroma of cancer as a way to potentiate current approaches. Tumor-associated macrophages (TAMs) are activated in the tumor microenvironment and facilitate disease progression by promoting angiogenesis and tumor cell growth, and by suppressing the adaptive immune response. We have recently identified a peptide that preferentially recognizes murine tumor-associated macrophage but not resting macrophage, other leukocytes, or tumor cells. In this work, we will prepare multivalent targeting constructs to deliver pro-apoptotic agents to TAMs in a mouse model of mammary cancer. In addition, we will develop analogous targeting peptides for human TAMs. These technologies will be combined in a new construct for targeted ablation of human TAMs. Our goal is to move this technology toward clinical development and to provide an adjuvant treatment that is effective even for women with hormone-unresponsive or triple negative breast cancer.
There is a great need for alternative methods to treat chemotherapy-resistant breast cancer. The main goal of this proposal is to develop drug delivery technologies targeted to tumor-associated cells that protect cancers from recognition by the immune system and from chemotherapies. We expect that these materials will potentiate the action of chemotherapies to make them more effective for eradicating tumor cells.
| Olden, Brynn R; Cheng, Yilong; Yu, Jonathan L et al. (2018) Cationic polymers for non-viral gene delivery to human T cells. J Control Release 282:140-147 |
| Wang, Christine E; Yumul, Roma C; Lin, Jonathan et al. (2018) Junction opener protein increases nanoparticle accumulation in solid tumors. J Control Release 272:9-16 |
| Peeler, David J; Thai, Salina N; Cheng, Yilong et al. (2018) pH-sensitive polymer micelles provide selective and potentiated lytic capacity to venom peptides for effective intracellular delivery. Biomaterials 192:235-244 |
| Yen, Albert; Cheng, Yilong; Sylvestre, Meilyn et al. (2018) Serum Nuclease Susceptibility of mRNA Cargo in Condensed Polyplexes. Mol Pharm 15:2268-2276 |
| Gustafson, Heather H; Olshefsky, Audrey; Sylvestre, Meilyn et al. (2018) Current state of in vivo panning technologies: Designing specificity and affinity into the future of drug targeting. Adv Drug Deliv Rev 130:39-49 |
| Lee, Daniel C; Lamm, Robert J; Prossnitz, Alex N et al. (2018) Dual Polymerizations: Untapped Potential for Biomaterials. Adv Healthc Mater :e1800861 |
| Ngambenjawong, Chayanon; Gustafson, Heather H; Sylvestre, Meilyn et al. (2017) A Facile Cyclization Method Improves Peptide Serum Stability and Confers Intrinsic Fluorescence. Chembiochem 18:2395-2398 |
| Ngambenjawong, Chayanon; Gustafson, Heather H; Pun, Suzie H (2017) Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv Drug Deliv Rev 114:206-221 |
| Comedy, Yolanda L; Gilbert, Juan E; Pun, Suzie H (2017) INVENTION IS NOT AN OPTION. Technol Innov 18:267-274 |
| Butterfield, Gabriel L; Lajoie, Marc J; Gustafson, Heather H et al. (2017) Evolution of a designed protein assembly encapsulating its own RNA genome. Nature 552:415-420 |
Showing the most recent 10 out of 23 publications
