The upconversion nanoparticle (UCNP)-based photodynamic therapy (PDT) agents are promising for deep-tissue cancer treatment because they may overcome current limitations due to the shallow penetration depth of visible light. However, limited blood circulation time and poor tumor-targeting capability challenge the therapeutic efficacy of UCNP-based PDT in vivo. Here, we demonstrate intravenous injectable stem-cell-membrane-camouflaged upconversion nanoarchitectures as a biomimetic tumor PDT platform. The biomimetic PDT system is constructed by fusing mesoporous-silica-encapsulated β-NaYF4:Yb3+,Er3+ UCNPs with stem-cell membranes. Translocation of the stem-cell membranes to the UCNPs led to the translation of multiple membrane components, bringing the membranes' long circulation and tumor-targeting capability to the resulting platform. Multiphotosensitizers were encapsulated and simultaneously activated by a 980 nm single laser because of the multicolor emission capability of the UCNP cores. In vitro and in vivo experiments demonstrate that this novel platform inherits the tumor-targeting properties of stem cells and exhibits remarkable accumulation at the tumor site. In vivo tumor PDT results show higher tumor inhibition efficacy by tail intravenous administration of this new photosensitizer-loaded system. This stem-cell-membrane-camouflaged upconversion nanoarchitecture provides artificial UCNPs with natural cell membranes and holds considerable promise for deep-tissue PDT cancer treatment by systemic administration.
Keywords: intravenous administration; photodynamic therapy; stem-cell membrane; tumor targeting; upconversion.