Abstract
The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.
Highlights
Cancer is a great threat to human health, and chemotherapy has been widely applied in clinics (Wu et al, 2016; Zheng et al, 2017; Cheng et al, 2018; Jiang et al, 2019; Dai et al, 2020; Zhou F. et al, 2021)
Both results indicated that Hyaluronic acid-based Docetaxel Micelle (HDM) was relatively unstable, and this phenomenon was mainly attributed to the leakage of DTX and would bring a decrease of hydrophobic interaction of micelle inner core, which resulted in a change of particle size
While there was no obvious change for Pluronic modified Hyaluronic acid-based Docetaxel Micelle (PHDM), this result indicated that the presence of F68 would enhance hydrophobic interaction between the drug and carrier and enhance its physical stability, which would reduce non-specific drug release and reduce systematic toxicity
Summary
Cancer is a great threat to human health, and chemotherapy has been widely applied in clinics (Wu et al, 2016; Zheng et al, 2017; Cheng et al, 2018; Jiang et al, 2019; Dai et al, 2020; Zhou F. et al, 2021). The development of nanoparticle drug delivery systems (NDDS) could reduce drug nonspecific distribution and increase tumor accumulation via the enhanced permeability and retention (EPR) effect (Zhang et al, 2017, 2018a,b, 2019). HA has been widely used for the construction of Copolymer Micelles for Chemo-Immunotherapy tumor-targeting nanoparticles because it could target CD44 receptors of tumor cells and facilitate cellular uptake (Huo et al, 2017; Cai et al, 2019; Zhang et al, 2020; Rangasami et al, 2021). The copolymer micelle is an amphiphilic molecule, which could self-assembly into a nanoparticle in aqueous solution (Zhang et al, 2016, 2017). Structure-modified HA with hydrophobic molecules could form grafted amphiphilic copolymers and be used for micelle construction. The HA-g-VES-grated copolymer is suitable for copolymer micelle construction
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