Thermosensitive Pluronic F127 Micelles for Piperlongumine Delivery: Selective ROS Amplification to Potentiate Cisplatin Efficacy in 3D Lung Cancer Spheroids
Year: 2026
Type: article
Abstract: Lung cancer remains a primary cause of cancer-related mortality worldwide, and cisplatin-based chemotherapy is often limited by its nonselective toxicity toward normal tissues and limited single-agent efficacy. To overcome these challenges, we developed a thermosensitive nanocarrier system utilizing Pluronic F127 (PF-127) to encapsulate Piperlongumine (PL)─a cancer-selective pro-oxidant reported to enhance cellular apoptotic responses to cisplatin treatment through ROS regulation and redox modulation. The PF-127 system leverages temperature-dependent self-assembly to form uniform spherical micelles with diameters below 100 nm at physiological temperature (37 °C), achieving a high drug loading efficiency (∼90%). Dynamic light scattering and transmission electron microscopy confirmed the formation of well-defined micelles and improved aqueous dispersibility of the hydrophobic PL. In vitro assays using A549 cells demonstrated that PL-loaded micelles significantly amplified intracellular ROS generation, promoting oxidative stress-associated apoptotic responses. This multidrug strategy markedly enhanced cisplatin-induced cytotoxicity in A549 cells. Crucially, in a 3D multicellular spheroid model, the treatment exhibited high cytotoxicity toward lung cancer spheroids (A549) while sparing normal lung fibroblast spheroids (MRC-5), consistent with the differential redox-handling capacities between malignant and healthy cells. These findings highlight the potential of ROS-amplified micellar delivery as a selective strategy to enhance cisplatin efficacy in lung cancer.
Source: ACS Applied Polymer Materials
Authors: Ju Yeong Jin, Do Hyun Hwangbo, Seong Min Choi, Young Ran Kim, Gyurin Kim, Eunji Lee
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1274079493, G1304040757, G1983722735
OpenAlex ID: W7169551171
