前药
体内
紫杉醇
化学
药理学
光敏剂
体外
活力测定
谷胱甘肽
活性氧
毒性
癌症研究
作者
Valentina Rapozzi,Francesca Moret,Luca Menilli,Andrea Guerrini,Daniele Tedesco,Marina Naldi,Manuela Bartolini,Mariachiara Gani,Sonia Zorzet,Marta Columbaro,Celeste Milani,Cecilia Martini,Claudia Ferroni,Greta Varchi
出处
期刊:Cancers
[MDPI AG]
日期:2022-02-10
卷期号:14 (4): 877-877
标识
DOI:10.3390/cancers14040877
摘要
Exploiting the tumor environment features (EPR effect, elevated glutathione, reactive oxygen species levels) might allow attaining a selective and responsive carrier capable of improving the therapeutic outcome. To this purpose, the in situ covalent binding of drugs and nanoparticles to circulating human serum albumin (HSA) might represent a pioneering approach to achieve an effective strategy. This study describes the synthesis, in vitro and in vivo evaluation of bioresponsive HSA-binding nanoparticles (MAL-PTX2S@Pba), co-delivering two different paclitaxel (PTX) prodrugs and the photosensitizer pheophorbide a (Pba), for the combined photo- and chemo-treatment of breast cancer. Stable and reproducible MAL-PTX2S@Pba nanoparticles with an average diameter of 82 nm and a PTX/Pba molar ratio of 2.5 were obtained by nanoprecipitation. The in vitro 2D combination experiments revealed that MAL-PTX2S@Pba treatment induces a strong inhibition of cell viability of MDA-MB-231, MCF7 and 4T1 cell lines, whereas 3D experiments displayed different trends: while MAL-PTX2S@Pba effectiveness was confirmed against MDA-MB-231 spheroids, the 4T1 model exhibited marked resistance. Lastly, despite using a low PTX-PDT regimen (e.g., 8.16 mg/Kg PTX and 2.34 mg/Kg Pba), our formulation showed to foster primary tumor reduction and curb lung metastases growth in 4T1 tumor-bearing mice, thus setting the basis for further preclinical validations.
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