Tumoral Acidic pH-Responsive cis-Diaminodichloroplatinum-Incorporated Cy5.5-PEG- g-A-HA Nanoparticles for Targeting Delivery of CDDP against Cervical Cancer

ACS Appl Mater Interfaces. 2018 Aug 15;10(32):26882-26892. doi: 10.1021/acsami.8b07425. Epub 2018 Jul 31.

Abstract

Cisplatin (CDDP) has been considered as one of the most effective anticancer drugs against cervical cancer, but the lack of selectivity of CDDP to tumor tissues often leads to serious toxic side effects. In this study, CDDP-incorporated Cy5.5-PEG- g-A-HA nanoparticles were prepared to endue CDDP the ability to selectively target tumors and fluorescence imaging in vivo. The nanoparticles exhibited a spherical shape with particle sizes between 216.4 and 281.5 nm and had a pH and Cl- concentration dependence on controlled and sustained CDDP release, which was favorable for nanoparticles to release more drugs at acidic tumor microenvironment. Cell biology experiments demonstrated that the nanoparticles had good biocompatibility and tumor targeting; the nanoparticles could selectively bind and internalize into HeLa cells and induce apoptosis, but lead to less cytotoxicity on NIH3T3 cells. What is more, the nanoparticles could be clearly fluorescent-imaged in vivo and showed an effective accumulation at the tumor site. Antitumor test in vivo displayed that the nanoparticles had good antitumor efficiency and low systemic toxicity which improved the life quality of mice. Hence, the CDDP-incorporated Cy5.5-PEG- g-A-HA nanoparticles were a potential delivery system for targeting delivery of CDDP against cervical cancer.

Keywords: CDDP; aldehyde hyaluronic acid; antitumor efficiency; cervical cancer; selective targeting.

MeSH terms

  • Animals
  • Antineoplastic Agents
  • Cell Line
  • Cisplatin
  • Drug Delivery Systems
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Nanoparticles*
  • Uterine Cervical Neoplasms

Substances

  • Antineoplastic Agents
  • Cisplatin