2. Academic Validation
  3. Smart dual responsive nanocarriers with reactive oxygen species amplification assisted synergistic chemotherapy against prostate cancer

Smart dual responsive nanocarriers with reactive oxygen species amplification assisted synergistic chemotherapy against prostate cancer

  • J Colloid Interface Sci. 2022 Sep 15;622:789-803. doi: 10.1016/j.jcis.2022.04.167.
Yupeng Guan 1,  Chengyuan Xing 1,  Tongyu Tong 1,  Xinyi Zhang 2,  Jun Li 3,  Huikun Chen 1,  Junfeng Zhu 4,  Yang Kang 5,  Jun Pang 6
Affiliations

Affiliations

  • 1 Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
  • 2 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
  • 3 Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
  • 4 Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China.
  • 5 Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China. Electronic address: kangy26@mail.sysu.edu.cn.
  • 6 Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China. Electronic address: pangjun2@mail.sysu.edu.cn.
PMID: 35544966 DOI: 10.1016/j.jcis.2022.04.167
Abstract

Conventional chemotherapy efficacy is impeded by poor water solubility, inferior tissue targeting, and severe systemic toxic effect. Synergistic chemotherapy has become prominent with the stimulus-response Drug Delivery system (DDS) to treat solid malignancies. The most popularly employed responsive stimulus is Reactive Oxygen Species (ROS), which is proven to primarily sensitize chemotherapy and enhance antitumor impact. In this study, we have successfully developed smart dual responsive nanocarriers with ROS self-amplification, particularly responding to disassemble under the high levels of ROS and esterase in the tumor microenvironment (TME) and to release docetaxel (DTX) efficiently. Additionally, we utilized palmitoyl ascorbate (PA) as a stabilizer by taking advantage of its amphiphilic structure. PA is also an excellent ROS generator that produces a large amount of hydrogen peroxide (H2O2) in TME to achieve ROS self-amplification. Also, elevated levels of ROS could continue to activate ROS-sensitive thioketal and make the remaining nanocarriers disassemble for sustaining the release of chemotherapeutics, realizing a positive feedback loop for ROS generation and ROS amplification, as well as sensitizing chemotherapy efficacy. The smart dual responsive nanocarriers may serve as a promising and prospective strategy for treating prostate Cancer and promoting synergistic Cancer therapy.

Keywords

Chemotherapy; Drug delivery; Prostate cancer; ROS-amplification; Smart nanocarriers; Tumor microenvironment.

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