Designing simple-structured nanomedicine without lacking key functionalities, thereby avoiding incomplete damage or relapse of tumor with the administration of a safe dose, is pivotal for successful cancer nanotherapy. We herein presented a nanomedicine of photodynamic therapy (PDT) that simply assembled amphiphilic macromolecules of poly-l-lysine conjugating with photosensitizers onto hydrophobic upconverting nanoparticles. We demonstrated that the nanoformulation, despite its simple structure and synthesis, simultaneously possesses multiple features, including substantial payload of photosensitizers, avid cellular internalization both in vitro and in vivo, efficient diffusion and broad distribution in tumor lesion, and potent fatality for cancer stem cells that are refractory to other therapy modalities. Because of the combination of these functionalities, the tumors in mice were eradicated and no relapse was observed after at least 40 days, just with an extremely low intraperitoneal injection dose of 5.6 mg/kg. Our results suggested a strategy for designing multifunctional nanomedicines with simple construct and efficacious therapeutic response and presented the promising potential of PDT for a radical cure of cancer.
Keywords: cancer stem cells; photodynamic therapy; poly--lysine; tumor penetration; upconversion nanoparticles.