Novel pH-sensitive nanoparticles based on prodrug strategy to delivery All-Trans Retinoic Acid for breast cancer

Developing chemotherapy with nanoparticle-based prodrugs provides promising strategies for improving the safety and delivery of anti-cancer drugs therapeutics and effective cancer treatment. Herein, we developed a pH-sensitive prodrug delivery system (All-Trans-Retinoic Acid (ATRA) grafted poly (β-a...

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Bibliographic Details
Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2022-11, Vol.219, p.112838, Article 112838
Main Authors: Li, Weinan, Gong, HeXin, Fu, Yuhan, Sun, Jialin, Wang, Yanhong
Format: Article
Language:English
Subjects:
All-Trans-Retinoic Acid
Breast cancer
Breast Neoplasms - drug therapy
Female
Humans
Hydrogen-Ion Concentration
Nanoparticles - chemistry
Pin1
Prodrug nanoparticles
Prodrugs - chemistry
Prodrugs - pharmacology
Tretinoin - pharmacology
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Summary:Developing chemotherapy with nanoparticle-based prodrugs provides promising strategies for improving the safety and delivery of anti-cancer drugs therapeutics and effective cancer treatment. Herein, we developed a pH-sensitive prodrug delivery system (All-Trans-Retinoic Acid (ATRA) grafted poly (β-amino esters) (PBAE) copolymers, ATRA-g-PBAE) for delivery of ATRA with some physicochemical and biological properties. The in vitro release of ATRA-g-PBAE prodrug nanoparticles (PNPs) was sustained-release and pH-sensitive. The cytotoxicity and uptake of different preparations in vitro were evaluated on MCF-7 cells at pH 7.4 and 5.5. The carrier PBAE had no cytotoxicity, and ATRA-g-PBAE PNPs could significantly inhibit cell growth at pH 5.5. MCF-7 cells treated with Cy5.5 grafted PBAE (Cy5.5-PBAE) showed stronger fluorescence signals at pH 5.5. Meanwhile, ATRA-g-PBAE PNPs entered the cell via a clathrin-mediated endocytic pathway. Subsequently, PBAE protonation facilitated the escape of PNPs from the lysosome and released the drug. ATRA-g-PBAE seems promising as a novel pH-sensitive prodrug to overcome the limitations of ATRA for breast cancer therapy. [Display omitted] •pH-sensitive prodrug nanoparticles were prepared and characterized.•After cellular uptake, prodrug nanoparticles could escape from lysosomes.•Intracellular, pH-responsive drug release was successfully achieved.
ISSN:0927-7765
1873-4367
1873-4367
DOI:10.1016/j.colsurfb.2022.112838