A critical barrier to effective cancer chemotherapy is the development of multidrug resistance (MDR) in cancer cells. The broad and long-term objective of this project is to develop advanced nanomedicinal approaches for the treatment of multidrug resistant cancers. We believe that nanomedicinal therapy, which can simultaneously deliver RNAi therapeutics to suppress MDR and chemotherapeutic agents to induce the death of cancer cells, will be of particular interest in addressing the challenge of MDR in cancer chemotherapy. Specifically, we will design and develop nanoparticulate platforms for the effective co-delivery of RNAi and anti-cancer agents with a synergistic drug ratio to taxane-resistant lung and prostate cancer cells, by using biodegradable and biocompatible polymers and lipids. The contribution of different drug-resistant proteins to cancer MDR will be compared. The physicochemical properties of the nanoparticles will also be optimized to overcome the physiological barriers in vivo, while keeping the co-delivery of RNAi and chemotherapy safe and effective. Furthermore, in the R00 independent phase, the nanoparticulate platform will be precisely engineered to control the temporal release of individual agents and to achieve targeted drug delivery. We hypothesize that the spatiotemporal controlled delivery of nanotherapeutics can maximize the desired effects of RNAi and anti-cancer agents for multidrug resistant cancers, while minimizing their toxic side effects. If successful, this project will lay the groundwork for wider applications of the nanotechnology-based targeted combination therapy for cancer and other diseases.
In this project we will use double-emulsion technology combined with self-assembly for nanoparticle synthesis. A library of the hybrid lipid-polymer nanoparticles will be formulated by tuning particle surface characteristics, components, drug loading/ratio, drug release profile, and targeting ligand density to optimize the co-delivery of RNAi and anti-cancer agents for multidrug resistant cancers (e.g., lung and prostate cancers). This nanoparticulate platform may be useful for the generation of versatile vehicles for targeted delivery of diverse drug combinations for a variety of therapeutic applications.
|Tao, Wei; Zhu, Xianbing; Yu, Xinghua et al. (2017) Black Phosphorus Nanosheets as a Robust Delivery Platform for Cancer Theranostics. Adv Mater 29:|
|Xu, Xiaoding; Saw, Phei Er; Tao, Wei et al. (2017) ROS-Responsive Polyprodrug Nanoparticles for Triggered Drug Delivery and Effective Cancer Therapy. Adv Mater 29:|
|Xu, Xiaoding; Wu, Jun; Liu, Yanlan et al. (2017) Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy. ACS Nano 11:2618-2627|
|Shi, Jinjun; Kantoff, Philip W; Wooster, Richard et al. (2017) Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17:20-37|
|Liu, Yanlan; Ji, Xiaoyuan; Liu, Jianhua et al. (2017) Tantalum Sulfide Nanosheets as a Theranostic Nanoplatform for Computed Tomography Imaging-Guided Combinatorial Chemo-Photothermal Therapy. Adv Funct Mater 27:|
|Zhu, Xi; Tao, Wei; Liu, Danny et al. (2017) Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery In Vitro and In Vivo. Theranostics 7:1990-2002|
|Xu, Xiaoding; Saw, Phei Er; Tao, Wei et al. (2017) Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy. Nano Lett 17:4427-4435|
|Liu, Yanlan; Ai, Kelong; Ji, Xiaoyuan et al. (2017) Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application To Protect Brain from Injury in Ischemic Stroke. J Am Chem Soc 139:856-862|
|Tao, Wei; Ji, Xiaoyuan; Xu, Xiaoding et al. (2017) Antimonene Quantum Dots: Synthesis and Application as Near-Infrared Photothermal Agents for Effective Cancer Therapy. Angew Chem Int Ed Engl 56:11896-11900|
|Xu, Xiaoding; Wu, Jun; Liu, Yanlan et al. (2016) Ultra-pH-Responsive and Tumor-Penetrating Nanoplatform for Targeted siRNA Delivery with Robust Anti-Cancer Efficacy. Angew Chem Int Ed Engl 55:7091-7094|
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