Glycogen-Linked TPGS Nanomicelles for Hypoxia-Responsive PD-L1 Targeting and Molecular Imaging of Breast Tumor

In the present work, we have modified glycogen (GLY) with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via the esterification reaction to obtain an amphiphilic polymer (TPGS-GLY). The TPGS-GLY conjugation was confirmed by FTIR and MALDI spectrometry. Furthermore, we prepared polymeric nanomicelles (MCs) encapsulated with palbociclib (PLB) using the solvent casting technique and surface decorated with an antiprogrammed cell death-ligand 1 (PD-L1) antibody to target hypoxic breast tumor. Several physicochemical characterizations have been performed. The MCs were found to be stable under storage, salt ion, and serum stability conditions. In vitro drug release profiles at distinct pH levels (5.5 and 7.4) demonstrate endosomal pH-triggered drug release within cells. The cytotoxicity investigation conducted on MCF-7 and MDA-MB-231 cells showed that the targeted MCs had cytotoxicity 30.94 times and 115.9 times higher than pure PLB, respectively. The cellular uptake, apoptosis, and reactive oxygen species studies have been performed for all of the prepared MCs. Ultrasound and photoacoustic imaging (USG/PAI) in DMBA-induced breast cancer rats revealed that the targeted MCs not only eliminated the tumor but also decreased the hypoxic tumor volume and hindered tumor angiogenesis. The clinical dye indocyanine green (ICG) has been utilized to evaluate the targeting efficiency of MCs toward breast tumors using USG/PAI imaging, demonstrating that targeted micelles has enhanced tumor localization. Furthermore, DiD dye has been employed to investigate organ biodistribution through IVIS imaging.