Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.
PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV. The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%. PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments. Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex. This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy. PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer.
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.
Paolo
P
Verderio
Paolo
P
Bonetti
Miriam
M
Colombo
Laura
L
Pandolfi
Davide
D
Prosperi
D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000493:pharmacokinetics*; D003593:Cytoplasm / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin