TY - JOUR
T1 - Injectable single-component peptide depot
T2 - Autonomously rechargeable tumor photosensitization for repeated photodynamic therapy
AU - Cho, Hong Jun
AU - Park, Sung Jun
AU - Jung, Woo Hyuk
AU - Cho, Yuri
AU - Ahn, Dong June
AU - Lee, Yoon Sik
AU - Kim, Sehoon
N1 - 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.
PY - 2020/11/24
Y1 - 2020/11/24
N2 - 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.
AB - 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.
KW - Activatable photosensitizer
KW - Internalizing RGD (iRGD)
KW - Molecular depot
KW - Photodynamic therapy
KW - Sustained release
UR - http://www.scopus.com/inward/record.url?scp=85096670834&partnerID=8YFLogxK
U2 - 10.1021/acsnano.0c06881
DO - 10.1021/acsnano.0c06881
M3 - Article
C2 - 33175520
AN - SCOPUS:85096670834
VL - 14
SP - 15793
EP - 15805
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 11
ER -