Abstract
Chemotherapy is an essential component of breast cancer therapy, but it is associated with serious side effects. Herein, a pluronic F68-based pH-responsive, and self-assembled nanomicelle system was designed to improve the delivery of paclitaxel (PTX) to breast cancer cells. Two pH-responsive pluronic F68-PTX conjugates i.e. succinoyl-linked conjugate (F68-SA-PTX) and cis-aconityl-linked conjugate (F68-CAA-PTX) were designed to respond the varying pH-environment in tumour tissue. Although both the linkers showed pH-sensitivity, the F68-CAA-PTX exhibited superior pH-sensitivity over the F68-SA-PTX and achieved a more selective release of PTX from the self-assembled nanomicelles. The prepared nanomicelles were characterized by dynamic light scattering, transmittance electron microscopy, differential scanning calorimetry and powder X-ray diffraction techniques. The anticancer activity of prepared nanomicelles and pure PTX were evaluated by 2D cytotoxicity assay against breast cancer cell line MDA-MB-231 and in the real tumour environments i.e. 3D tumor spheroids of MDA-MB-231 cells. The highest cytotoxicity effect of PTX was observed with F68-CAA-PTX nanomicelles followed by F68-SA-PTX and free PTX. Further, the F68-CAA-PTX nanomicelles also induced significant apoptosis with a combination of increase in ROS generation, decrease in the depolarisation of MMP and G2/M cell cycle arrest. These observed results provide a new insight for breast cancer treatment using pluronic nanomicelles.