Combined and targeted drugs delivery system for colorectal cancer treatment: Conatumumab decorated, reactive oxygen species sensitive irinotecan prodrug and quercetin co-loaded nanostructured lipid carriers

Drug Deliv. 2022 Dec;29(1):342-350. doi: 10.1080/10717544.2022.2027573.

Abstract

Purpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and this study aimed to develop a conatumumab decorated, irinotecan prodrug and quercetin co-loaded delivery system for combined and targeted colorectal cancer treatment.

Methods: A conatumumab (C) decorated, irinotecan prodrug (I-p) and quercetin (Q) co-encapsulated NLC (C I-p/Q NLC) was developed. In vitro and in vivo antitumor efficiency of NLC was evaluated on CRC cells and mice xenograft.

Results: The results showed that the HT-29 cells uptake of C I-p/Q NLC was over 70%. Reactive oxygen species (ROS) sensitive irinotecan prodrug formulation showed improved drug release ability in hypoxic conditions. C I-p/Q NLC showed significantly higher cytotoxicity than non-decorated NLC, single drug-loaded NLC and free drugs. In vivo studies in a CRC-bearing model corroborated the capability of nanoparticles for the inhibition of cancer, leading to a reduction of tumor growth without systemic toxicity.

Conclusion: The conatumumab decorated, ROS sensitive prodrug contained combination nano-system is a promising platform for CRC therapy.

Keywords: Colorectal cancer; irinotecan prodrug; lipid nanoparticles; reactive oxygen species sensitive.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Drug Carriers / chemistry
  • Drug Combinations
  • Drug Liberation
  • Drug Stability
  • Drug Synergism
  • HT29 Cells
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / pharmacology*
  • Lipids / chemistry
  • Mice
  • Nanoparticle Drug Delivery System / chemistry*
  • Nanostructures
  • Particle Size
  • Prodrugs
  • Quercetin / administration & dosage
  • Quercetin / pharmacology*
  • Reactive Oxygen Species
  • Surface Properties
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Drug Carriers
  • Drug Combinations
  • Lipids
  • Nanoparticle Drug Delivery System
  • Prodrugs
  • Reactive Oxygen Species
  • conatumumab
  • Irinotecan
  • Quercetin