Two-Stage SN38 Release from a Core-Shell Nanoparticle Enhances Tumor Deposition and Antitumor Efficacy for Synergistic Combination with Immune Checkpoint Blockade.

ABSTRACT: Long-circulating nanomedicines efficiently deliver chemotherapies to tumors to reduce general toxicity. However, extended blood circulation of nanomedicines can increase drug exposure to leukocytes and lead to hematological toxicity. Here, we report a two-stage release strategy to enhance the drug deposition and antitumor efficacy of OxPt/SN38 core-shell nanoparticles with a hydrophilic oxaliplatin (OxPt) prodrug coordination polymer core and a lipid shell containing a hydrophobic cholesterol-conjugated SN38 prodrug (Chol-SN38). By conjugating cholesterol to the phenol group of SN38 via an acetal linkage and protecting the 20-hydroxy position with a trimethylsilyl (TMS) group, Chol-SN38 releases SN38 in two stages via esterase-catalyzed cleavage of the acetal linkage in the liver followed

SUBMITTER: Jiang X 

PROVIDER: S-EPMC9798857 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature