Open AccessChemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy
Author(s) -
Zhang Da,
Wu Ming,
Cai Zhixiong,
Liao Naishun,
Ke Kun,
Liu Hongzhi,
Li Ming,
Liu Gang,
Yang Huanghao,
Liu Xiaolong,
Liu Jingfeng
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201700648
Subject(s) - microvesicle , nanocarriers , doxorubicin , chemistry , photodynamic therapy , phthalocyanine , photosensitizer , tumor hypoxia , drug , combinatorial chemistry , biophysics , drug delivery , nanotechnology , materials science , photochemistry , pharmacology , biochemistry , organic chemistry , microvesicles , chemotherapy , biology , medicine , microrna , gene , radiation therapy , genetics
A novel metal–organic particle (MOP) based nanodrug formed by mild self‐assembly of chemotherapeutic drugs, including banoxantrone and doxorubicin, through Cu(II)‐mediated coordination effects, is reported. In this nanodrug, Cu(II) acts as a bridge to join AQ4N and DOX, and then, self‐assembly of [‐AQ4N‐Cu(II)‐(DOX) 2 ‐Cu(II)‐] n complexes forms nanosized MOPs (referred to as ADMOPs) through multiple interactions including host–metal–guest coordination, hydrophobic interactions, π‐stacking, and van der Waals force. The ADMOPs reported here have several important features over conventional drugs, including tumor microenvironment pH‐sensitive drug release that can be tracked by “turning on” the fluorescence of AQ4N or DOX through proton competition with Cu(II) to break the coordination bonds and much deeper penetration into solid tumors via microvesicle‐mediated intercellular transfer. Most strikingly, the ADMOPs can serve as stimuli‐responsive nanocarriers to efficiently load the photosensitizer phthalocyanine due to their inherent highly porous characteristics. Thus, the ADMOPs significantly enhance the chemotherapeutic efficacy by “on‐demand” photodynamic therapy, which further induces a hypoxic environment that enhances the reduction of AQ4N to systematically increase the therapeutic efficiency. Taken together, the designed ADMOPs composed of chemotherapeutic drugs may serve as a potential programmable controlled synergistic agent for cancer therapy.