Functionalized Tumor Cell Membrane-Camouflaged Photo-Activatable Nanoparticle for Spatiotemporal Antitumor Therapy

Systemically administered drugs often lead to off-target delivery, inducing compromised therapy efficacy and significant toxicity. We hypothesize that improving the drugs’ targeting and spatiotemporally controllable releasing capabilities can enhance the anti-tumor effects and reduce the side effects. To achieve this goal, a functionalized biomimetic photoactivatable nanotherapeutics (U-ACPT@MM) is designed. The U-ACPT@MM comprises of melittin, a pore-forming protein, functionalized within the 4T1 tumor cell membrane, camouflaged with lanthanide-doped upconversion nanoparticles (UCNPs) conjugated with 9-aminocamptothecin (ACPT), a chemotherapeutics, by photolabile linkers. The melittin-functionalized 4T1 tumor cell membrane not only enables homologous targeting ability to 4T1 tumors, but also increases both the concentration of melittin and ACPT within tumor. Meanwhile, upon 808 nm irradiation, the UV emissions from UCNPs cut off photolabile linker to release ACPT. The synergism of enhanced tumor targeting and combinational therapeutic effects of ACPT and melittin leads to significant inhibition of 4T1 tumor and lung metastasis with reduced side effects in vivo. Thus, our study provides a promising functionalized biomimetic photoactivatable nano-therapeutical strategy for cancer therapy.