Combination Treatment of Cervical Cancer Using Folate-Decorated, pH-Sensitive, Carboplatin and Paclitaxel Co-Loaded Lipid-Polymer Hybrid Nanoparticles

Drug Des Devel Ther. 2020 Feb 26:14:823-832. doi: 10.2147/DDDT.S235098. eCollection 2020.

Abstract

Purpose: Cervical cancer is one of the most common causes of death among women globally. Combinations of cisplatin, paclitaxel, bevacizumab, carboplatin, topotecan, and gemcitabine are recommended as first-line therapies.

Methods: This study focuses on the development of folate-decorated, pH-sensitive lipid-polymer hybrid nanoparticles (LPNs). Loading carboplatin (CBP) and paclitaxel (PTX), LPNs were expected to combine the therapeutic effects of CBP and PTX, thus show synergistic ability on cervical cancer.

Results: FA-CBP/PTX-LPNs showed the sizes of 169.9 ± 5.6 nm, with a narrow size distribution of 0.151 ± 0.023. FA-CBP/PTX-LPNs exhibited pH-responsive drug release, high cellular uptake efficiency (66.7 ± 3.1%), and prominent cell inhibition capacity (23 ± 1.1%). In vivo tumor distribution and tumor inhibition efficiency of FA-CBP/PTX-LPNs was the highest, with no obvious body weight lost.

Conclusion: High tumor distribution and remarkable antitumor efficiency obtained using in vitro as well as in vivo models further proved the FA-CBP/PTX-LPNs is a promising tool for cervical cancer therapy.

Keywords: carboplatin; cervical cancer; folate; lipid-polymer hybrid nanoparticles; pH-sensitive; paclitaxel.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / pharmacology*
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Ligands
  • Lipids / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology*
  • Polymers / chemistry
  • Structure-Activity Relationship
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Ligands
  • Lipids
  • Polymers
  • Folic Acid
  • Carboplatin
  • Paclitaxel