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

Abstract

Systemically administered drugs can often lead to off-target delivery, inducing compromised therapy efficacy and significant toxic side effects. We hypothesize that increasing drug targeting and improving spatiotemporally drug-controlled release can enhance the anti-tumor effects and reduce the side effects of chemotherapy drugs. To achieve this goal, 9-aminocamptothecin (ACPT), a chemotherapy drug, is conjugated with lanthanide-doped upconversion nanoparticles (UCNPs) via a photolabile linker and camouflaged with melittin-functionalized 4T1 tumor cell membrane, named U-ACPT@MM, for 4T1 tumor therapy research. 4T1 cell membranes loaded with melittin have the homologous targeting ability to 4T1 tumors and can increase the antitumor ability of chemotherapeutic drugs. Meanwhile, upon 808 nm irradiation, short wavelength UV emission of UCNPs can cut off photolabile linker to release chemotherapy drugs ACPT. Such synergism of U-ACPT@MM leads to significant inhibition of 4T1 tumor growth and lung metastasis with reduced side effects in vivo. Our study provides a promising drug delivery strategy for cancer therapy that combined homotypic targeting and spatiotemporal control release.

Note:
Funding declaration: This work was supported by the National Key Research and Development Program of China (2021YFA1101501), and the National Natural Science Foundation of China (No 82172083).

Conflict of Interests: The authors declare no competing interests.

Ethical Approval: All animal studies were approved by The Institutional Animal Care and Use Committee of Huazhong University of Science and Technology (IACUC Number:3276).

Keywords: Functionalized tumor cell membrane, Lanthanide upconversion nanoparticles, Photo-activatable cancer therapy, Homologous targeting