Programmable aggregation of photosensitizer in multi- organelles for cancer therapy
Abstract
The precise spatiotemporal control of subcellular drug distribution remains a central therapeutic challenge. Here, a stimulus-responsive aggregation-induced emission (AIE) photosensitizer (TBPBB) is utilized to achieve controllable aggregation switching between two distinct organelles that enables sequential dual-organelle destruction. Actively delivered to tumors by hypoxia-tropic Bacillus subtilis, TBPBB first aggregates at mitochondria, generating reactive oxygen species (ROS) under light exposure, triggering bond cleavage to form a second AIE species (TBP) that re-aggregates at lipid droplets and generates ROS more efficiently. The sequential targeting and destruction of dual organelles, together with ROS-triggered bacterial lysis, induce ferroptosis, apoptosis and antitumor immunity, collectively amplifying therapeutic efficacy. In a breast cancer model, this system achieves a 92.4% tumour growth inhibition with negligible organ toxicity. This paradigm establishes a generalizable strategy for programmable aggregation of therapeutic agents and multi-organelle destruction, readily adaptable to other organelle pairs by substituting the stimuli-responsive moieties or targeting fragments.
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BibTeX
@misc{kong2026programmable,
title = {{Programmable aggregation of photosensitizer in multi- organelles for cancer therapy}},
author = {Lin Kong and Yun-hao Chen and Shun-yi Wang and Wei He and Meng-li Liu and Zheng Zhao and Ben Zhong Tang},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009252/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009252/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Programmable aggregation of photosensitizer in multi- organelles for cancer therapy
AU - Lin Kong
AU - Yun-hao Chen
AU - Shun-yi Wang
AU - Wei He
AU - Meng-li Liu
AU - Zheng Zhao
AU - Ben Zhong Tang
PY - 2026
DA - 2026/09/22
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009252/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009252/v1
AB - The precise spatiotemporal control of subcellular drug distribution remains a central therapeutic challenge. Here, a stimulus-responsive aggregation-induced emission (AIE) photosensitizer (TBPBB) is utilized to achieve controllable aggregation switching between two distinct organelles that enables sequential dual-organelle destruction. Actively delivered to tumors by hypoxia-tropic Bacillus subtilis, TBPBB first aggregates at mitochondria, generating reactive oxygen species (ROS) under light exposure, triggering bond cleavage to form a second AIE species (TBP) that re-aggregates at lipid droplets and generates ROS more efficiently. The sequential targeting and destruction of dual organelles, together with ROS-triggered bacterial lysis, induce ferroptosis, apoptosis and antitumor immunity, collectively amplifying therapeutic efficacy. In a breast cancer model, this system achieves a 92.4% tumour growth inhibition with negligible organ toxicity. This paradigm establishes a generalizable strategy for programmable aggregation of therapeutic agents and multi-organelle destruction, readily adaptable to other organelle pairs by substituting the stimuli-responsive moieties or targeting fragments.
ER -