A Versatile Plasma Membrane Engineered Cell Vehicle for Contact-Cell-Enhanced Photodynamic Therapy

In this paper, a plasma membrane engineering approach is reported for tumor targeting drug delivery and contact-cell-enhanced photodynamic therapy (“CONCEPT”) by anchoring functionalized conjugates to cell vehicles. The membrane anchoring conjugates are comprised of a positively charged tetra-arginine peptide sequence, a palmitic-acid-based membrane insertion moiety, and a lysine linker whose ε-amine is modified with camptothecin (CPT), protoporphyrin IX (PpIX), or fluorescein (FAM). The amphipathic CPT, PpIX, or FAM conjugates (short as aCPT, aPpIX, or aFAM, respectively) can easily and steadily anchor or coanchor on the cell membrane of RAW264.7 cells (short as RCs), red blood cells, or mesenchymal stem cells. After anchoring aPpIX in RC cells, the tumor targeting ability and therapeutic effect of aPpIX-anchored RC cells (short as aPRCs) is demonstrated in vitro and in vivo. Importantly, aPRCs exhibit the “CONCEPT” effect, which can enhance the therapeutic efficacy and reduce side effects at the single cell level. Due to the good tumor-targeting ability, aPRCs can efficiently inhibit the tumor growth with no systemic toxicity after photoirradiation by photodynamic therapy.