Scheme 1

Schematic illustration for MSC-guided sustained intratumoral drug delivery (a) The intratumorally implantable MSC composed of a drug-infusing needle and a reservoir was fabricated, and the cathepsin B-cleavable pro-apoptotic prodrug (SMAC-P-FRRG-DOX)-encapsulating LNPs (ApoLNPs) were loaded in the reservoir of MSC. The MSC-guided intratumoral administration allows ApoLNPs to be directly infused into deep tumor tissues in a persistent manner. b Compared to the intravenous or instant intratumoral administration, the MSC-guided administration was expected to secure more tumor-exclusive accumulation and uniform intratumoral distribution of drugs by diminishing their undesirable delivery to normal tissues or rapid leakage from tumors. c ApoLNPs would be slowly released at the center of tumor tissues through the MSC guidance and evenly distributed to entire tissues via their gradual diffusion mechanism