Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 219, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2022.112838
Keywords
All-Trans-Retinoic Acid; Prodrug nanoparticles; Pin1; Breast cancer
Funding
- Science Foundation Project of Heilongjiang Province of China [LH2021H098]
- National Natural Science Foundation of China [82074025]
- Heilongjiang Touyan Innovation Team Program, Heilongjiang Traditional Chinese Medicine Administration [ZYW2022-086]
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Developing a pH-sensitive prodrug delivery system using nanoparticle carriers shows promising results in inhibiting breast cancer cell growth and releasing drugs at lower pH levels.
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 (beta-amino esters) (PBAE) co-polymers, 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 facil-itated 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.
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