Sorafenib Encapsulated Poly(ester amide) Nanoparticles for Efficient and Biosafe Prostate Cancer Therapy

ACS Biomater Sci Eng. 2024 Jul 8;10(7):4336-4346. doi: 10.1021/acsbiomaterials.4c00345. Epub 2024 Jun 8.

Abstract

Prostate cancer (PCa) with a high incidence worldwide is a serious threat to men's health. Despite the continuous development of treatment strategies for PCa in recent years, the long-term prognosis of patients is still poor. Hence, the discovery and development of novel, secure, and efficient therapeutic approaches hold significant clinical significance. Although sorafenib (SOR) displays potential as a therapeutic option for PCa, its clinical efficacy is hindered by drug resistance, limited water solubility, and rapid metabolism. Therefore, we proposed to prepare nanoparticles (named SOR@8P4 NPs) utilizing the phenylalanine-based poly(ester amide) polymer (8P4) as the drug carrier to enhance the solubility and drug stability of SOR and improve the therapeutic targeting and bioavailability. SOR@8P4 NPs had high stability and showed acid-responsive drug release at the acidic tumor microenvironment. Additionally, SOR@8P4 NPs demonstrated more remarkable anticancer, antimetastatic, and antiproliferative abilities in vitro, compared with those of free drugs. SOR@8P4 NPs showed high tumor targeting and significantly inhibited tumor growth in vivo. In summary, the drug delivery system of SOR@8P4 NPs provides new ideas for the clinical treatment of PCa.

Keywords: drug delivery; nanoparticles; poly(ester amide); prostate cancer; sorafenib.

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Amides / therapeutic use
  • Animals
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / chemistry
  • Drug Liberation
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Polyesters / chemistry
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Sorafenib* / chemistry
  • Sorafenib* / pharmacokinetics
  • Sorafenib* / pharmacology
  • Sorafenib* / therapeutic use

Substances

  • Sorafenib
  • Antineoplastic Agents
  • Polyesters
  • Drug Carriers
  • Amides