Feasibility of Using Poly[oligo(ethylene glycol) Methyl Ether Methacrylate] as Tumor-Targeted Carriers of Diagnostic Drugs

Kohei Sano, Koki Umemoto, Haruka Miura, Satoshi Ohno, Kyohei Iwata, Rin Kawakami, Masayuki Munekane, Toshihide Yamasaki, Daniel Citterio, Yuki Hiruta, Takahiro Mukai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) is a water-soluble polymer in which multiple short ethylene glycol (EG) chains are grafted along the hydrophobic methyl methacrylate backbone. We investigated whether POEGMA could be used as a drug carrier for tumor diagnosis. For this purpose, we synthesized POEGMA derivatives with different molecular weights (11, 21, and 30 kDa) and EG side chain lengths, and labeled them with radioisotopes (indium-111; 111In) or fluorescence dyes (indocyanine green; ICG) as signal emitters. Fluorescence microscopy studies using colon26 tumor cells treated with ICG-labeled POEGMA derivatives revealed that the POEGMA derivatives were efficiently taken up by tumor cells compared to the control, poly(ethylene glycol) (PEG), suggesting the involvement of a POEGMA-specific cellular uptake pathway. The radiolabeled POEGMA derivatives were intravenously injected into colon26 tumor-bearing mice, and their biodistribution was evaluated. As the molecular weight of POEGMA derivatives increased, the circulating time was prolonged, and their accumulation in the liver and spleen increased. In particular, 21 kDa POEGMA showed excellent tumor uptake and tumor-to-normal tissue ratio. Therefore, we investigated the effect of EG chain length on the tumor uptake of POEGMA (21 kDa) and observed high tumor uptake for all POEGMA derivatives; however, relatively higher abdominal uptake was observed for POEGMA derivatives with longer EG chain lengths. Finally, in vivo fluorescence imaging using optimized POEGMA derivatives labeled with ICG clearly visualized the tumor tissues, suggesting that the POEGMA derivatives could be suitable drug carriers for sensitive tumor diagnosis.

Original languageEnglish
Pages (from-to)4734-4740
Number of pages7
JournalACS Applied Polymer Materials
Volume4
Issue number7
DOIs
Publication statusPublished - 2022 Jul 8

Keywords

  • biodistribution
  • drug carrier
  • poly[oligo(ethylene glycol) methyl ether methacrylate]
  • tumor imaging
  • water-soluble polymer

ASJC Scopus subject areas

  • Process Chemistry and Technology
  • Polymers and Plastics
  • Organic Chemistry

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