PLGA Nanoplatform\nfor the Hypoxic Tumor Delivery:\nFolate Targeting, Therapy, and Ultrasound/Photoacoustic Imaging

Effective targeting of breast tumors is critical for\nimproving\ntherapeutic outcomes in breast cancer treatment. Additionally, hypoxic\nbreast cancers are difficult to treat due to resistance toward chemotherapeutics,\npoor vascularity, and enhanced angiogenesis, which complicate effective\ndrug delivery and therapeutic response. Addressing this formidable\nchallenge requires designing a drug delivery system capable of targeted\ndelivery of the anticancer agent, inhibition of efflux pump, and suppression\nof the tumor angiogenesis. Here, we have introduced Palbociclib (PCB)-loaded\nPLGA nanoparticles (NPs) consisting of chitosan-folate (CS-FOL) for\nfolate receptor-targeted breast cancer therapy. The developed NPs\nwere below 219 nm with a smooth, spherical surface shape. The entrapment\nefficiencies of NPs were achieved up to 85.78 ± 1.8%. Targeted\nNPs demonstrated faster drug release at pH 5.5, which potentiated\nthe therapeutic efficacy of NPs due to the acidic microenvironment\nof breast cancer. In vitro cellular uptake study in MCF-7 cells confirmed\nthe receptor-mediated endocytosis of targeted NPs. In vivo ultrasound\nand photoacoustic imaging studies on rats with hypoxic breast cancer\nshowed that targeted NPs significantly reduced tumor growth and hypoxic\ntumor volume, and suppressed angiogenesis.