Cationic Conjugated Polymer/Hyaluronan-Doxorubicin Complex for Sensitive Fluorescence Detection of Hyaluronidase and Tumor-Targeting Drug Delivery and Imaging.
Hyaluronidase (HAase) is becoming a new type of tumor marker since it has been demonstrated to be overexpressed in various kinds of cancer cells. In this study, we described a novel fluorescence method for sensitive, rapid, and convenient HAase detection and tumor-targeting drug delivery and imaging, using a probe prepared by electrostatic assembly of a cationic conjugated polymer (CCP) and anionic hyaluronan (HA) conjugated with the anticancer drug doxorubicin (Dox). The CCP we used was poly{[9,9-bis(6'-(N,N,N-diethylmethylammonium)hexyl)-2,7-fluorenylene ethynylene]-alt-co-[2,5-bis(3'-(N,N,N-diethylmethylammonium)-1'-oxapropyl)-1,4-phenylene]} tetraiodide (PFEP). HA is a natural mucopolysaccharide that can be hydrolyzed by HAase into fragments with low molecular weights. In the PFEP/HA-Dox complex, the fluorescence of PFEP was efficiently quenched due to electron transfer from PFEP to Dox. After the PFEP/HA-Dox complex was exposed to HAase or was taken up by cancer cells through the specific binding between HA and CD44 receptor, HA was degraded by HAase to release the Dox, leading to the recovery of PFEP fluorescence to the "turn-on" state. Moreover, the degree of fluorescence recovery was quantitatively correlated with the concentrations of HAase. Compared with many previously reported methods, our work did not require laborious multiple modifications of HA that may affect the activity of HAase. This point, combined with the excellent optoelectronic property of conjugated polymer, endowed this method with high sensitivity (detection limit: 0.075 U/mL), high specificity, and rapid response, making it applicable for reliable and routine detection of HAase. This fluorescent probe was successfully utilized to detect HAase levels in human urine samples; furthermore, it can also be employed as a multifunctional system by realizing tumor-targeting drug delivery and cell imaging simultaneously. The development of this fluorescence method showed promising potential for early tumor diagnosis and therapy based on HAase detection.
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Yanqin
Y
Huang
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Caixia
C
Song
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Huichang
H
Li
Department of Ophthalmology, Zhongda Hospital, Southeast University , Nanjing 211189, China.
Rui
R
Zhang
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Rongcui
R
Jiang
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Xingfen
X
Liu
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Guangwei
G
Zhang
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Quli
Q
Fan
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.
Lianhui
L
Wang
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications , Nanjing 210023, China.|Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech) , 30 South Puzhu Road, Nanjing 211816, China.
Wei
W
Huang
D002412:Cations; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000652:urine*; D007454:Iodides; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000648:ultrastructure; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D002412:Cations; D007454:Iodides; D011108:Polymers; D004317:Doxorubicin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase
conjugated polymer; fluorescence; hyaluronan-doxorubicin; hyaluronidase; imaging