EGFR-Targeted and NIR-Triggered Lipid-Polymer Hybrid Nanoparticles for Chemo-Photothermal Colorectal Tumor Therapy

Int J Nanomedicine. 2024 Sep 18:19:9689-9705. doi: 10.2147/IJN.S473473. eCollection 2024.

Abstract

Background: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.

Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.

Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.

Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy.

Keywords: Cetuximab; Chemo-photothermal therapy; Indocyanine green; Nanoparticles; Targeted cancer therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Camptothecin / administration & dosage
  • Camptothecin / chemistry
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cetuximab* / chemistry
  • Cetuximab* / pharmacokinetics
  • Cetuximab* / pharmacology
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / therapy
  • Drug Carriers / chemistry
  • ErbB Receptors* / metabolism
  • Humans
  • Indocyanine Green* / administration & dosage
  • Indocyanine Green* / chemistry
  • Indocyanine Green* / pharmacokinetics
  • Indocyanine Green* / pharmacology
  • Infrared Rays
  • Irinotecan* / administration & dosage
  • Irinotecan* / chemistry
  • Irinotecan* / pharmacokinetics
  • Irinotecan* / pharmacology
  • Lecithins / chemistry
  • Lipids / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles* / chemistry
  • Photothermal Therapy* / methods
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • ErbB Receptors
  • Irinotecan
  • Cetuximab
  • Indocyanine Green
  • EGFR protein, human
  • Polyethylene Glycols
  • Camptothecin
  • Drug Carriers
  • Polymers
  • Antineoplastic Agents
  • Lecithins
  • Lipids