A versatile tumor-targeted drug-delivery system based on IR808-modified nanoparticles, its co-loading with PTX and R848 and its extraordinary antitumor efficacy.

Autor: Guo Y; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com.; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110000, China. liudongchun@outlook.com., Li M; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com., Liu X; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com., Wang X; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com., Zhang Z; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com., Liu D; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110000, China. liudongchun@outlook.com., Wang X; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. xtaowang@163.com.
Jazyk: angličtina
Zdroj: Nanoscale [Nanoscale] 2024 Nov 28; Vol. 16 (46), pp. 21431-21446. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1039/d4nr02837f
Abstrakt: Nearly all antitumor drugs can benefit greatly from effective tumor-targeted delivery for improved therapeutic efficacy and reduced toxic side effects. However, the vast majority of tumor-targeting ligands can only target specific tumor cells that highly express the corresponding receptors and thus are only applicable to limited tumor types. Heptamethine cyanines with medium cyclohexene and medium Cl atoms, such as IR780 and IR808, have shown an unusual ability to indiscriminately accumulate into virtually all tumor types. In this study, IR808 was conjugated with DSPE-mPEG 2000 -NH 2 , and the resultant DSPE-PEG 2000 -IR808 (DP-IR808) in combination with TPGS successfully encapsulated paclitaxel (PTX) and immunomodulator R848 into nanoparticles with a small particle size of 150.20 nm, negative charge of -16.50 mV, rod-like morphology, and PTX loading content of 31.6%. The obtained DP-IR808@PTX-R848 NPs rapidly accumulated in 4T1 tumors with a tumor/liver fluorescence ratio of 1.71, and it demonstrated a significant photothermal effect and could be directly used for NIR imaging. The DP-IR808@PTX-R848 NPs achieved a high tumor inhibition rate of 94%, a mean survival time of >90 d, and a tumor-free survival percentage of 57%. To the best of our knowledge, this was the first time that nanoparticles were modified with heptamethylcyanine molecules. The nanoparticles system based on DSPE-PEG-IR808, which integrates tumor-targeted drug delivery, in vivo infrared imaging and photothermal therapy, is expected to become a versatile drug-delivery platform for tumor therapy.
Databáze: MEDLINE