The multifunctional micelle-based targeting nanotherapeutics to be developed in this project offer an opportunity to deliver high concentration of cytotoxic drugs (e.g. doxorubicine), molecularly targeted drugs (e.g. bortezomib [Velcade(R)], a proteosome inhibitor) as well as therapeutic radionuclides such as 131I to the tumor sites while sparing normal organs, thus greatly enhance the anti-tumor effects and lessen the systemic side effects of these drugs. As a result, we expect patients with advanced non- Hodgkin lymphoma (both T- and B-cell type) or solid tumors will benefit from such novel nanotherapies. In addition, such multifunctional nanoplatform can also be used as tumor imaging agents. Our nanotherapeutic platform is unique and comprised of oligocholic acid based micelles with drugs loaded inside and cancer targeting ligands decorating the micelle surface. We believe the addition of LLP2A, a lymphoma targeting ligand, to the nanotherapeutics can facilitate the intracellular delivery of the nanocarrier to the tumor cells in vivo and therefore will greatly enhance their anti-tumor efficacies. In this proposed research, biodistribution properties (imaging) and therapeutic efficacies of such targeting nanoparticles will be evaluated in both transgenic mouse lymphoma models and spontaneous canine lymphoma. This research will lead to the development of more efficacious and less toxic multifunctional targeting nanoformulations of bortexomib (a proteasome inhibitor), doxorubicin (a DNA intercalate), and therapeutic radionuclide 131I, all of which are expected to be useful in the treatment of many cancer types including non-Hodgkin lymphoma (NHL). If successful, this therapeutic approach can be applied to many other cancer types as well and therefore will have a great impact in the survival of cancer patients in the United States and around the world.
The multifunctional micelle-based targeting nanotherapeutics to be developed in this project offer an opportunity to deliver high concentration of cytotoxic drugs, molecularly targeted drugs as well as therapeutic radionuclides such as 131I to the tumor sites while sparing normal organs, thus greatly enhance the anti-tumor effects and lessen the systemic side effects of these drugs. Amphiphilic polymers will be designed, synthesized, and optimized for efficient loading of bortezomib or doxorubicin to form nanoparticles. These nanotherapeutics will be evaluated for their anti-tumor efficacies in transgenic mouse lymphoma model and in companion dogs with spontaneous lymphomas.
|Luo, Yan; Wu, Hao; Feng, Caihong et al. (2017) ""One-Pot"" Fabrication of Highly Versatile and Biocompatible Poly(vinyl alcohol)-porphyrin-based Nanotheranostics. Theranostics 7:3901-3914|
|Xiao, Kai; Lin, Tzu-Yin; Lam, Kit S et al. (2017) A facile strategy for fine-tuning the stability and drug release of stimuli-responsive cross-linked micellar nanoparticles towards precision drug delivery. Nanoscale 9:7765-7770|
|Xiao, Wenwu; Suby, Nell; Xiao, Kai et al. (2017) Extremely long tumor retention, multi-responsive boronate crosslinked micelles with superior therapeutic efficacy for ovarian cancer. J Control Release 264:169-179|
|Yang, Xixiao; Xue, Xiangdong; Luo, Yan et al. (2017) Sub-100nm, long tumor retention SN-38-loaded photonic micelles for tri-modal cancer therapy. J Control Release 261:297-306|
|Lin, Tzu-Yin; Guo, Wenchang; Long, Qilai et al. (2016) HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy. Theranostics 6:1324-35|
|Wang, Yan; Xiao, Wenwu; Zhang, Yonghong et al. (2016) Optimization of RGD-Containing Cyclic Peptides against ?v?3 Integrin. Mol Cancer Ther 15:232-40|
|Xiao, Kai; Li, Yuan-Pei; Wang, Cheng et al. (2015) Disulfide cross-linked micelles of novel HDAC inhibitor thailandepsin A for the treatment of breast cancer. Biomaterials 67:183-93|
|Zhang, Pengfei; Zam, Azhar; Jian, Yifan et al. (2015) In vivo wide-field multispectral scanning laser ophthalmoscopy-optical coherence tomography mouse retinal imager: longitudinal imaging of ganglion cells, microglia, and Müller glia, and mapping of the mouse retinal and choroidal vasculature. J Biomed Opt 20:126005|
|Li, Yuanpei; Xiao, Kai; Zhu, Wei et al. (2014) Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers. Adv Drug Deliv Rev 66:58-73|
|Li, Yuanpei; Lin, Tzu-Yin; Luo, Yan et al. (2014) A smart and versatile theranostic nanomedicine platform based on nanoporphyrin. Nat Commun 5:4712|
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