Injectable single-component peptide depot: Autonomously rechargeable tumor photosensitization for repeated photodynamic therapy

Hong Jun Cho, Sung Jun Park, Woo Hyuk Jung, Yuri Cho, Dong June Ahn, Yoon Sik Lee, Sehoon Kim

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


The general practice of photodynamic therapy (PDT) comprises repeated multiple sessions, where photosensitizers are repeatedly administered prior to each operation of light irradiation. To address potential problems arising from the total overdose of photosensitizer by such repeated injections, we here introduce an internalizing RGD peptide (iRGD) derivative (Ppa-iRGDC-BK01) that self-aggregates into an injectable single-component supramolecular depot. Ppa-iRGDC-BK01 is designed as an in situ self-implantable photosensitizer so that it forms a depot by itself upon injection, and its molecular functions (cancer cell internalization and photosensitization) are activated by sustained release, tumor targeting, and tumor-selective proteolytic/reductive cleavage of the iRGD segment. The experimental and theoretical studies revealed that when exposed to body temperature, Ppa-iRGDC-BK01 undergoes thermally accelerated self-assembly to form a supramolecular depot through the hydrophobic interaction of the Ppa pendants and the reorganization of the interpeptide hydrogen bonding. It turned out that the self-aggregation of Ppa-iRGDC-BK01 into a depot exerts a multiple-quenching effect on the photosensitivity to effectively prevent nonspecific phototoxicity and protect it from photobleaching outside the tumor, while enabling autonomous tumor rephotosensitization by long sustained release, tumor accumulation, and intratumoral activation over time. We demonstrate that depot formation through a single peritumoral injection and subsequent quintuple laser irradiations at intervals resulted in complete eradication of the tumor. During the repeated PDT, depot-implanted normal tissues around the tumor exhibited no phototoxic damage under laser exposure. Our approach of single-component photosensitizing supramolecular depot, combined with a strategy of tumor-targeted therapeutic activation, would be a safer and more precise operation of PDT through a nonconventional protocol composed of one-time photosensitizer injection and multiple laser irradiations.

Original languageEnglish
Pages (from-to)15793-15805
Number of pages13
JournalACS nano
Issue number11
Publication statusPublished - 2020 Nov 24

Bibliographical note

Funding Information:
This work was supported by the grants from the National Research Foundation of Korea (2017M3A9D8029942 and 2017R1A2B3006770) and Korea Research Institute of Standards and Science (KRISS-2018-GP2018-0018) for the KIST intramural program.

Publisher Copyright:
© 2020 American Chemical Society.


  • Activatable photosensitizer
  • Internalizing RGD (iRGD)
  • Molecular depot
  • Photodynamic therapy
  • Sustained release

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy


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