The efficiency of MSC-based targeted AIE nanoparticles for gastric cancer diagnosis and treatment: An experimental study

Mesenchymal stem cells (MSCs), due to their tumor tropism, are strongly recruited by various solid tumors and mobilized by inflammatory signals in the tumor microenvironment. However, effective cellular uptake is critical for MSC-based drug delivery. In this study, we synthesized a spherical copolymer, polyethylenimine-poly(epsilon-caprolactone), with aggregation-induced emission (AIE) material and the anticancer drug, paclitaxel, coloaded onto its inner core. This was followed by the addition of a transactivator of transcription (TAT) peptide, a type of cell-penetrating peptide, to modify the nanoparticles (NPs). Finally, the MSCs were employed to carry the TAT-modified AIE-NPs drug to the tumor sites and assist in simultaneous cancer diagnosis and targeted tumor therapy. In vitro, the TAT-modified AIE-NPs showed good biocompatibility, targeting, and stability in an aqueous solution besides high drug-loading and encapsulation efficiency. In vitro, the AIE-NPs exhibited a controllable release under a mildly acidic environment. The in vivo and in vitro studies showed high antitumor efficacy and low cytotoxicity of the AIE-NP drug, whereas biodistribution confirmed the tumor tropism of MSCs. To summarize, the MSC-based AIE-NP drugs loaded with TAT possessed good biocompatibility and high antitumor efficacy via the enhanced NP-drug uptake. In addition, the tumor tropism of MSCs provided selective drug uptake by the tumor cells and thus reduced the systemic side effects.