Plasma Amine Oxidase-Induced Nanoparticle-to-Nanofiber Geometric Transformation of an Amphiphilic Peptide for Drug Encapsulation and Enhanced Bactericidal Activity

ACS Appl Mater Interfaces. 2020 Jan 29;12(4):4323-4332. doi: 10.1021/acsami.9b21296. Epub 2020 Jan 14.

Abstract

Patients with cancer have reduced immune function and are susceptible to bacterial infection after surgery, chemotherapy, or radiotherapy. Spherical nanoparticles formed by the self-assembled peptide V6K3 can be used as carriers for poorly soluble antitumor drugs to effectively deliver drugs into tumor cells. V6K3 was designed to achieve nanoparticle-to-nanofiber geometric transformation under induction by plasma amine oxidase (PAO). PAO is commercially available and functionally similar to lysyl oxidase (LO), which is widely present in serum. After the addition of fetal bovine serum (FBS) or PAO, the secondary structure of the peptide changed, while the spherical nanoparticles stretched and transformed into nanofibers. The conversion of the self-assembled morphology reveals the susceptibility of this amphiphilic peptide to subtle chemical modifications and may lead to promising strategies to control self-assembled architecture via enzyme induction. Enzymatically self-assembled V6K3 had bactericidal properties after PAO addition that were surprisingly superior to those before PAO addition, enabling this peptide to be used to prevent infection. The amphiphilic peptide V6K3 displayed antitumor properties and low toxicity in mammalian cells, demonstrating good biocompatibility, as well as bactericidal properties, to prevent bacterial contamination. These advantages indicate that enzymatically self-assembled V6K3 has great biomedical application potential in cancer therapy.

Keywords: amphiphilic peptide; antibacterial activity; drug encapsulation; geometric transformation; plasma amine oxidase.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • HeLa Cells
  • Humans
  • Mice
  • Monoamine Oxidase / metabolism*
  • NIH 3T3 Cells
  • Nanofibers* / chemistry
  • Nanofibers* / therapeutic use
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Peptides* / chemistry
  • Peptides* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Drug Carriers
  • Peptides
  • Monoamine Oxidase