TY - JOUR
T1 - Single Small Molecule-Assembled Mitochondria Targeting Nanofibers for Enhanced Photodynamic Cancer Therapy In Vivo
AU - Lin, Kai
AU - Ma, Zhao
AU - Li, Jin
AU - Tang, Menghuan
AU - Lindstrom, Aaron
AU - Ramachandran, Mythili
AU - Zhu, Shaoming
AU - Lin, Tzu yin
AU - Zhang, Lanwei
AU - Li, Yuanpei
N1 - Funding Information:
K.L. and Z.M. contributed equally to this work. The authors thank the support from NIH/NCI (R01CA199668, R01CA232845), NIH/NIDCR (R01DE029237), NIH/NICHD (R01HD086195), and UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30CA093373). The authors also appreciate the access to the Molecular Pharmacology Shared Resources funded by the CCSG.
PY - 2020
Y1 - 2020
N2 - Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but its therapeutic effects are limited by the nonselective subcellular localization and poor intratumoral retention of small-molecule photosensitizes. Here a fiber-forming nanophotosensitizer (PQC NF) that is composed of mitochondria targeting small molecules of amphiphilicity is reported. Harnessing the specific mitochondria targeting, the light-activated PQC NFs produce approximately 110-fold higher amount of reactive oxygen species in cells than free photosensitizers and can dramatically induce mitochondrial disruption to trigger intense apoptosis, showing 20–50 times better in vitro anticancer potency than traditional photosensitizers. As fiber-shaped nanomaterials, PQC NFs also demonstrated a long-term retention in tumor sites, solving the challenge of rapid clearance of small-molecule photosensitizers from tumors. With these advantages, PQC NFs achieve a 100% complete cure rate in both subcutaneous and orthotopic oral cancer models with the administration of only a single dose. This type of single small molecule-assembled mitochondria targeting nanofibers offers an advantageous strategy to improve the in vivo therapeutic effects of conventional PDT.
AB - Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but its therapeutic effects are limited by the nonselective subcellular localization and poor intratumoral retention of small-molecule photosensitizes. Here a fiber-forming nanophotosensitizer (PQC NF) that is composed of mitochondria targeting small molecules of amphiphilicity is reported. Harnessing the specific mitochondria targeting, the light-activated PQC NFs produce approximately 110-fold higher amount of reactive oxygen species in cells than free photosensitizers and can dramatically induce mitochondrial disruption to trigger intense apoptosis, showing 20–50 times better in vitro anticancer potency than traditional photosensitizers. As fiber-shaped nanomaterials, PQC NFs also demonstrated a long-term retention in tumor sites, solving the challenge of rapid clearance of small-molecule photosensitizers from tumors. With these advantages, PQC NFs achieve a 100% complete cure rate in both subcutaneous and orthotopic oral cancer models with the administration of only a single dose. This type of single small molecule-assembled mitochondria targeting nanofibers offers an advantageous strategy to improve the in vivo therapeutic effects of conventional PDT.
KW - mitochondria targeting
KW - nanofiber
KW - photodynamic therapy
KW - self-assembly
KW - small-molecule drug conjugate
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U2 - 10.1002/adfm.202008460
DO - 10.1002/adfm.202008460
M3 - Article
AN - SCOPUS:85097605147
JO - Advanced Materials for Optics and Electronics
JF - Advanced Materials for Optics and Electronics
SN - 1057-9257
ER -