TY - JOUR
T1 - Hypoxia-Responsive Polyprodrug Nanocarriers for Near-Infrared Light-Boosted Photodynamic Chemotherapy
AU - Dutta, Debabrata
AU - Zhou, Qinghao
AU - Mukerabigwi, Jean Felix
AU - Lu, Nannan
AU - Ge, Zhishen
N1 - Publisher Copyright:
©
PY - 2021/11/8
Y1 - 2021/11/8
N2 - The hypoxia environment inside tumors is tightly associated with tumor growth, metastasis, and drug resistance. However, the heterogonous distribution of hypoxic areas limits the efficacy of hypoxia-activatable drug delivery systems. Herein, we report the hypoxia-activable block copolymer polyprodrugs, which are composed of poly(ethylene glycol) (PEG) and copolymerized segments of ortho-nitrobenzyl-linked camptothecin (CPT) methacrylate and 2-(piperidin-1-yl)ethyl methacrylate (PEMA) monomers. After self-assembly in aqueous solution, indocyanine green (ICG) photosensitizers were encapsulated to formulate ICG-loaded micellar nanoparticles (ICG@CPTNB) for near-infrared (NIR) light-boosted photodynamic therapy (PDT), tumor hypoxia aggravation, and responsive drug activation. Through intravenous injection and prolonged blood circulation, the nanoparticles can accumulate into tumor efficiently. Tumor acidity-triggered charge transition of PEMA units remarkably promotes cellular internalization of the nanoparticles. Upon exposure to NIR laser irradiation, ICG inside the nanoparticles produced reactive oxygen species (ROS) along with local hypothermia. Simultaneously, the oxygen consumption during ROS production aggravated the intratumoral hypoxia, which amplified hypoxia-responsive self-immolative CPT release from the nanoparticles. The combined photodynamic chemotherapy using hypoxia-responsive polyprodrug nanoparticles, ICG@CPTNB, overcomes the limitations of single therapy of hypoxia-activable prodrugs or PDT, which remarkably improves the efficiency of tumor growth suppression.
AB - The hypoxia environment inside tumors is tightly associated with tumor growth, metastasis, and drug resistance. However, the heterogonous distribution of hypoxic areas limits the efficacy of hypoxia-activatable drug delivery systems. Herein, we report the hypoxia-activable block copolymer polyprodrugs, which are composed of poly(ethylene glycol) (PEG) and copolymerized segments of ortho-nitrobenzyl-linked camptothecin (CPT) methacrylate and 2-(piperidin-1-yl)ethyl methacrylate (PEMA) monomers. After self-assembly in aqueous solution, indocyanine green (ICG) photosensitizers were encapsulated to formulate ICG-loaded micellar nanoparticles (ICG@CPTNB) for near-infrared (NIR) light-boosted photodynamic therapy (PDT), tumor hypoxia aggravation, and responsive drug activation. Through intravenous injection and prolonged blood circulation, the nanoparticles can accumulate into tumor efficiently. Tumor acidity-triggered charge transition of PEMA units remarkably promotes cellular internalization of the nanoparticles. Upon exposure to NIR laser irradiation, ICG inside the nanoparticles produced reactive oxygen species (ROS) along with local hypothermia. Simultaneously, the oxygen consumption during ROS production aggravated the intratumoral hypoxia, which amplified hypoxia-responsive self-immolative CPT release from the nanoparticles. The combined photodynamic chemotherapy using hypoxia-responsive polyprodrug nanoparticles, ICG@CPTNB, overcomes the limitations of single therapy of hypoxia-activable prodrugs or PDT, which remarkably improves the efficiency of tumor growth suppression.
UR - https://www.scopus.com/pages/publications/85118689775
U2 - 10.1021/acs.biomac.1c01152
DO - 10.1021/acs.biomac.1c01152
M3 - 文章
C2 - 34689560
AN - SCOPUS:85118689775
SN - 1525-7797
VL - 22
SP - 4857
EP - 4870
JO - Biomacromolecules
JF - Biomacromolecules
IS - 11
ER -