1. Lactoferrin/phenylboronic acid-functionalized hyaluronic acid nanogels loading doxorubicin hydrochloride for targeting glioma
Feng Shao, Cihui Tian, Qineng Ping, Yanyu Xiao, Sajid Asghar, Ziyi Hu, Zhipeng Chen, Mei Zhang Carbohydr Polym . 2021 Feb 1;253:117194. doi: 10.1016/j.carbpol.2020.117194.
Herein, lactoferrin (Lf)/phenylboronic acid (PBA)-functionalized hyaluronic acid nanogels crosslinked with disulfide-bond crosslinker was developed as a reduction-sensitive dual-targeting glioma therapeutic platform for doxorubicin hydrochloride (DOX) delivery (Lf-DOX/PBNG). Spherical Lf-DOX/PBNG with optimized physicochemical properties was obtained, and it could rapidly release the encapsulated DOX under high glutathione concentration. Moreover, enhanced cytotoxicity, superior cellular uptake efficiency, and significantly improved brain permeability of Lf-DOX/PBNG were observed in cytological studies compared with those of DOX solution, DOX-loaded PBA functionalized nanogels (DOX/PBNG), and Lf modified DOX-loaded nanogels (Lf-DOX/NG). The pharmacokinetic study exhibited that the area under the curve of DOX/PBNG, Lf-DOX/NG, and Lf-DOX/PBNG increased by 8.12, 4.20 and 4.32 times compared with that of DOX solution, respectively. The brain accumulation of Lf-DOX/PBNG was verified in biodistribution study to be 12.37 and 4.67 times of DOX solution and DOX/PBNG, respectively. These findings suggest that Lf-DOX/PBNG is an excellent candidate for achieving effective glioma targeting.
2. Efficient detection doxorubicin hydrochloride using CuInSe2@ZnS quantum dots and Ag nanoparticles
Min Yang, Hong Hao, Cunjin Wang, Huanxian Shi, Jun Fan, Guohua Mi Spectrochim Acta A Mol Biomol Spectrosc . 2020 Nov 5;241:118673. doi: 10.1016/j.saa.2020.118673.
Doxorubicin hydrochloride (DOX) is an effective anthracycline anticancer drug. However, the exceeded taken up could induce several side-effects such as cardiotoxicity, alopecia. Therefore, the level of DOX needs to be closely monitored to avoid the occurrence of its side-effects. Herein, we report a novel core CuInSe2- shell ZnS quantum dots (CuInSe2@ZnS, QDs) and Ag nanoparticles (NPs) fluorescence sensor based on the surface plasmon resonance effect (SPR) of Ag NPs. The CuInSe2@ZnS QDs were prepared by water phase reflux method with the 3-mercaptopropionic acid (MPA) as stabilizer and ligand. The fluorescence intensity of CuInSe2@ZnS QDs/Ag NPs significantly reduced by DOX, which is mainly based on the electrostatic interaction between the DOX and fluorescence sensors. The inhibition of photoluminescence (ln F0/F) was linearly relationship to the concentration of DOX in the range of 2-100 μM with the detection limit as low as 0.05 μM. The as-prepared sensor has a high selectivity and sensitivity to DOX. Furthermore, the new sensor has been successfully applied to the determination of DOX in human serum samples with satisfactory results. Our work provides a clue for developing a novel CuInSe2@ZnS QDs/Ag NPs based fluorescence sensor for DOX detection.
3. Highly Efficient Encapsulation of Doxorubicin Hydrochloride in Metal-Organic Frameworks for Synergistic Chemotherapy and Chemodynamic Therapy
Lijia Yao, Wenqian Cao, Guodong Qian, Yuanjing Cui, Ying Tang ACS Biomater Sci Eng . 2021 Oct 11;7(10):4999-5006. doi: 10.1021/acsbiomaterials.1c00874.
Iron-based metal-organic frameworks (MOFs) have been reported to have great potential for encapsulating doxorubicin hydrochloride (DOX), which is a frequently used anthracycline anticancer drug. However, developing a facile approach to realize high loading capacity and efficiency as well as controlled release of DOX in MOFs remains a huge challenge. Herein, we synthesized water-stable MIL-101(Fe)-C4H4through a microwave-assisted method. It was found the nano-MOFs acted as nanosponges when soaked in a DOX alkaline aqueous solution with a loading capacity experimentally up to 24.5 wt %, while maintaininga loading efficiency as high as 98%. The mechanism of the interaction between DOX and nanoMOFs was investigated by absorption spectra and density functional theory (DFT) calculations, which revealed that the deprotonated DOX was electrostatically adsorbed to the unsaturated Fe3OCl(COO)6·H2O (named Fe3trimers). In addition, the as-designed poly(ethylene glycol-co-propylene glycol) (F127) modified nanoparticles (F127-DOX-MIL) could be decomposed under the stimulation of glutathione (GSH) and ATP. As a result, DOX and Fe(III) ions were released, and they could undergo a Fenton-like reaction with the endogenous H2O2to generate the highly toxic hydroxyl radical (·OH). The in vitro experiments indicated that F127-DOX-MIL could cause remarkable Hela cells inhibition through chemotherapy and chemodynamic therapy. Our study provides a new strategy to design a GSH/ATP-responsive drug-delivery nanosystem for chemo/chemodynamic therapy.