Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro

Int J Mol Sci. 2024 Mar 6;25(5):3069. doi: 10.3390/ijms25053069.

Abstract

The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology-Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.

Keywords: Lewis lung carcinoma; cytotoxicity; drug; star-like copolymer.

MeSH terms

  • Acrylic Resins*
  • Antineoplastic Agents* / therapeutic use
  • Doxorubicin / chemistry
  • Drug Carriers / chemistry
  • Micelles
  • Polymers* / chemistry
  • Water

Substances

  • Polymers
  • poly-N-isopropylacrylamide
  • Water
  • Antineoplastic Agents
  • Doxorubicin
  • Drug Carriers
  • Micelles
  • Acrylic Resins

Grants and funding

We thank the Brandenburg program “Strengthening technological and application-oriented research at scientific institutions (StaF Directive)” (FullDrug, 85037298).