Abstract
Objectives: The aim of this study was to formulate fluorescent-labeled targeted immunoliposome to visualize the delivery and distribution of drugs in real-time.
Methods: In this study, fluorescent-labeled liposomes were decorated with anti-HER2 VHH or Herceptin to improve the monitoring of intracellular drug delivery and tumor cell tracking with minimal side effects. The conjugation efficiency of antibodies was analyzed by SDS-PAGE silver staining. In addition, the physicochemical characterization of liposomes was performed using DLS and TEM. Finally, confocal microscopy visualized nanoparticles in the target cells.
Results: Quantitative and qualitative methods characterized the intracellular uptake of 110±10 nm particles with near 70% conjugation efficiency. In addition, live-cell trafficking during hours of incubation was monitored by wide-field microscopy imaging. The results show that the fluorescent- labeled nanoparticles can specifically bind to HER2-positive breast cancer with minimal off-target delivery.
Conclusion: These nanoparticles can have several applications in personalized medicine, especially drug delivery and real-time visualization of cancer therapy. Moreover, this method also can be applied in the targeted delivery of contrast agents in imaging and thermotherapy.
Keywords: Fluorescent liposome, HER2, live-cell imaging, targeted delivery, VHH, wide-field microscopy.
[http://dx.doi.org/10.1039/C9RA08192E]
[http://dx.doi.org/10.1021/acs.nanolett.9b04853] [PMID: 31928014]
[http://dx.doi.org/10.7150/jca.4925] [PMID: 23386910]
[http://dx.doi.org/10.1039/C8TB03351J] [PMID: 32254773]
[http://dx.doi.org/10.1021/acscentsci.9b01139] [PMID: 32123729]
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.086] [PMID: 20149431]
[http://dx.doi.org/10.1080/1061186X.2018.1497039] [PMID: 29972336]
[http://dx.doi.org/10.1016/j.canlet.2019.01.045] [PMID: 30763718]
[http://dx.doi.org/10.2174/1389557518666180903150928] [PMID: 30179131]
[http://dx.doi.org/10.1007/978-3-030-01775-0_8]
[http://dx.doi.org/10.1080/1061186X.2018.1564923] [PMID: 30596291]
[http://dx.doi.org/10.2174/187221107779814104] [PMID: 19075873]
[http://dx.doi.org/10.1002/anie.201809641] [PMID: 30341792]
[http://dx.doi.org/10.1021/acsnano.7b05908] [PMID: 28953351]
[http://dx.doi.org/10.1088/0957-4484/19/36/365603] [PMID: 21828874]
[http://dx.doi.org/10.1016/S0009-3084(02)00105-6] [PMID: 12426077]
[http://dx.doi.org/10.1021/acsami.8b22693] [PMID: 31056910]
[http://dx.doi.org/10.1007/s12195-015-0381-z] [PMID: 25798204]
[http://dx.doi.org/10.1039/C6MD00614K] [PMID: 30108759]
[http://dx.doi.org/10.1016/j.matchemphys.2018.08.028]
[http://dx.doi.org/10.1021/jacs.8b02619] [PMID: 29727175]
[http://dx.doi.org/10.1016/j.ejps.2018.11.023] [PMID: 30471410]
[http://dx.doi.org/10.3389/fchem.2014.00069] [PMID: 25202689]
[http://dx.doi.org/10.1159/000055396] [PMID: 11694782]
[http://dx.doi.org/10.1056/NEJM200103153441101] [PMID: 11248153]
[http://dx.doi.org/10.1038/onc.2008.207] [PMID: 18591932]
[http://dx.doi.org/10.1089/1536859041224334] [PMID: 15312305]
[http://dx.doi.org/10.1007/s00253-007-1142-2] [PMID: 17704915]
[http://dx.doi.org/10.3109/08820139.2010.542228] [PMID: 21244216]
[http://dx.doi.org/10.1186/s12951-020-00644-z] [PMID: 32522291]
[http://dx.doi.org/10.1006/prep.1997.0834] [PMID: 9518456]
[http://dx.doi.org/10.1002/cmmi.1697] [PMID: 27307214]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.09.031] [PMID: 28917937]
[http://dx.doi.org/10.1002/adhm.201300533] [PMID: 24408356]
[http://dx.doi.org/10.1002/adhm.201400421] [PMID: 25336437]
[http://dx.doi.org/10.1186/s12934-014-0140-1] [PMID: 25223348]
[http://dx.doi.org/10.1016/j.ab.2019.113491] [PMID: 31676284]
[http://dx.doi.org/10.3390/molecules25235672] [PMID: 33271886]
[http://dx.doi.org/10.1016/B978-0-12-820016-2.00008-2]
[http://dx.doi.org/10.1016/j.ijpharm.2017.12.047] [PMID: 29294324]
[http://dx.doi.org/10.3390/ijms19123859] [PMID: 30518027]
[http://dx.doi.org/10.1016/j.jconrel.2017.04.028] [PMID: 28442407]
[http://dx.doi.org/10.1016/j.ejps.2018.07.044] [PMID: 30041027]
[http://dx.doi.org/10.1016/j.nano.2018.01.009] [PMID: 29410110]
[http://dx.doi.org/10.21873/anticanres.14619] [PMID: 33109536]
[http://dx.doi.org/10.1007/s12195-017-0481-z] [PMID: 31719864]
[http://dx.doi.org/10.1016/j.molimm.2018.01.010] [PMID: 29549861]
[http://dx.doi.org/10.1186/s13568-016-0201-4] [PMID: 27112931]
[http://dx.doi.org/10.1080/21691401.2018.1549063] [PMID: 30810413]
[http://dx.doi.org/10.1016/j.actbio.2020.04.029] [PMID: 32417267]
[http://dx.doi.org/10.1016/j.jconrel.2020.04.010] [PMID: 32276005]
[http://dx.doi.org/10.2174/1566524018666180416101522] [PMID: 29663884]
[http://dx.doi.org/10.2174/1389450117666160208144143] [PMID: 26853324]
[http://dx.doi.org/10.3390/ijms19010195] [PMID: 29315231]
[http://dx.doi.org/10.1016/j.nano.2018.12.010] [PMID: 30654182]
[http://dx.doi.org/10.1007/s00280-009-1132-4] [PMID: 19779718]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1093] [PMID: 16357174]
[http://dx.doi.org/10.3791/58896] [PMID: 30855567]
[http://dx.doi.org/10.1016/j.yexcr.2012.03.004] [PMID: 22440788]
[http://dx.doi.org/10.1016/j.biomaterials.2013.10.001] [PMID: 24139763]
[http://dx.doi.org/10.1016/j.ejpb.2017.12.009] [PMID: 29274374]
[http://dx.doi.org/10.2147/IJN.S269630] [PMID: 33122905]
[http://dx.doi.org/10.1088/1361-6528/ab19d3] [PMID: 30991371]
[http://dx.doi.org/10.1080/1061186X.2019.1648479] [PMID: 31339374]
[http://dx.doi.org/10.3389/fonc.2020.01182] [PMID: 32793488]
[http://dx.doi.org/10.1039/C9NR00207C] [PMID: 30888379]