Cross-Linked Polyphenol-Based Drug Nano-Self-Assemblies Engineered to Blockade Prostate Cancer Senescence
- Prashanth K.B. NageshPrashanth K.B. NageshDepartment of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Prashanth K.B. Nagesh,
- Pallabita ChowdhuryPallabita ChowdhuryDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Pallabita Chowdhury,
- Elham HatamiElham HatamiDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Elham Hatami,
- Sonam KumariSonam KumariDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Sonam Kumari,
- Vivek Kumar KashyapVivek Kumar KashyapDepartment of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Vivek Kumar Kashyap,
- Manish K. TripathiManish K. TripathiDepartment of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Manish K. Tripathi,
- Santosh WaghSantosh WaghDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Santosh Wagh,
- Bernd MeibohmBernd MeibohmDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Bernd Meibohm,
- Subhash C. ChauhanSubhash C. ChauhanDepartment of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Subhash C. Chauhan,
- Meena JaggiMeena JaggiDepartment of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Meena Jaggi, and
- Murali M. Yallapu*Murali M. Yallapu*Mailing address: Department of Immunology and Microbiology, 5300 North L Street, Room 2.249, McAllen, TX 78504. Phone: (956) 296-1705. Fax No: (956)-296-1325. E-mail: [email protected]Department of Microbiology and Immunology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, United StatesDepartment of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United StatesMore by Murali M. Yallapu
Abstract
Cellular senescence is one of the prevailing issues in cancer therapeutics that promotes cancer relapse, chemoresistance, and recurrence. Patients undergoing persistent chemotherapy often develop drug-induced senescence. Docetaxel, an FDA-approved treatment for prostate cancer, is known to induce cellular senescence which often limits the overall survival of patients. Strategic therapies that counter the cellular and drug-induced senescence are an unmet clinical need. Towards this an effort was made to develop a novel therapeutic strategy that targets and removes senescent cells from the tumors, we developed a nanoformulation of tannic acid–docetaxel self-assemblies (DSAs). The construction of DSAs was confirmed through particle size measurements, spectroscopy, thermal, and biocompatibility studies. This formulation exhibited enhanced in vitro therapeutic activity in various biological functional assays with respect to native docetaxel treatments. Microarray and immunoblot analysis results demonstrated that DSAs exposure selectively deregulated senescence associated TGFβR1/FOXO1/p21 signaling. Decrease in β-galactosidase staining further suggested reversion of drug-induced senescence after DSAs exposure. Additionally, DSAs induced profound cell death by activation of apoptotic signaling through bypassing senescence. Furthermore, in vivo and ex vivo imaging analysis demonstrated the tumor targeting behavior of DSAs in mice bearing PC-3 xenograft tumors. The antisenescence and anticancer activity of DSAs was further shown in vivo by inhibiting TGFβR1 proteins and regressing tumor growth through apoptotic induction in the PC-3 xenograft mouse model. Overall, DSAs exhibited such advanced features due to a natural compound in the formulation as a matrix/binder for docetaxel. Overall, DSAs showed superior tumor targeting and improved cellular internalization, promoting docetaxel efficacy. These findings may have great implications in prostate cancer therapy.
Cited By
This article is cited by 3 publications.
- Prashanth K. B. Nagesh, Pallabita Chowdhury, Elham Hatami, Shashi Jain, Nirnoy Dan, Vivek Kumar Kashyap, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu. Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-57932-9
- Sumeet S. Chauhan, Advait B. Shetty, Elham Hatami, Pallabita Chowdhury, Murali M. Yallapu. Pectin-Tannic Acid Nano-Complexes Promote the Delivery and Bioactivity of Drugs in Pancreatic Cancer Cells. Pharmaceutics 2020, 12 (3) , 285. https://doi.org/10.3390/pharmaceutics12030285
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