Recently, we have developed nanocrystals capable of delivering anticancer drugs. These nanocrystals with possess low toxicity, high drug loading ratio, and overcome multidrug resistance (MDR) in cancer cells in vitro and in vivo. The overall goal of this research proposal is to further develop and investigate multifunctional nanocrystals for MDR cancer therapy. The scientific basis for this proposal originated from our three-phase nanoparticle engineering (3PNE) method recently developed, which includes phase 1, amorphous precipitate;phase 2, hydrated amorphous aggregate;and phase 3, stabilized nanocrystals (NCs). The 3PNE has been applied to the development of rod-shaped NCs for effective anticancer drug delivery. To achieve this goal, we propose three aims:
specific aim 1, to examine the mechanisms of the NCs for their ability to enhance physical stability, overcome MDR, and their in vivo behavior;
specific aim 2, to develop NCs that carry target ligands to deliver PTX to tumor;
and specific aim 3, to establish the NCs for co-delivering a hydrophobic drug (i.e., Paclitaxel) and a hydrophilic anti-cancer drug (i.e., 5-fluorouracil) to synergistically kill tumor cells through different cellular mechanisms. Accomplishing these specific aims will further develop efficient nano-drug carriers for the treatment of cancer, particularly MDR cancer.
This project is relevant to cancer therapy in public health in two ways. First, it has the potential to develop novel nanocrystals (NCs) as an anticancer drug carrier for the efficient treatment of multidrug resistance (MDR) in cancer. Moreover, if successful, the development of new NCs in this proposal has the potential to deliver hydrophobic drugs for the treatment other diseases.
|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|
|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|
|Liu, Qi; Zhu, Hongda; Liu, Yun et al. (2018) BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma. Cancer Immunol Immunother 67:299-310|
|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|
|Miao, Lei; Li, Jingjing; Liu, Qi et al. (2017) Transient and Local Expression of Chemokine and Immune Checkpoint Traps To Treat Pancreatic Cancer. ACS Nano 11:8690-8706|
|Ma, Yan; Wang, Yuhua; Xu, Zhenghong et al. (2017) Extreme low dose of 5-fluorouracil reverses MDR in cancer by sensitizing cancer associated fibroblasts and down-regulating P-gp. PLoS One 12:e0180023|
|Goodwin, Tyler J; Huang, Leaf (2017) Investigation of phosphorylated adjuvants co-encapsulated with a model cancer peptide antigen for the treatment of colorectal cancer and liver metastasis. Vaccine 35:2550-2557|
|Satterlee, Andrew B; Attayek, Peter; Midkiff, Bentley et al. (2017) A dosimetric model for the heterogeneous delivery of radioactive nanoparticles In vivo: a feasibility study. Radiat Oncol 12:54|
|Miao, Lei; Liu, Qi; Lin, C Michael et al. (2017) Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors. Cancer Res 77:719-731|
|Goodwin, Tyler J; Shen, Limei; Hu, Mengying et al. (2017) Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid structures of liver metastases and prolong survival. Biomaterials 141:260-271|
Showing the most recent 10 out of 45 publications