Sequential activation of anticancer therapy triggered by tumor microenvironment-selective imaging

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Combined imaging and anticancer therapy show promise but face challenges with nonspecific signals and drug distribution.
• Targeted delivery systems are needed to improve specificity in cancer treatment and imaging.

Purpose of the Study:

• To develop a graphene oxide (GO)-based nanosheet system for selective cancer visualization and triggered anticancer therapy.
• To exploit matrix metalloproteinase (MMP) overexpression in the tumor microenvironment for targeted activation.

Main Methods:

• Designed a GO-based nanosheet system (IPGO/BF) loaded with a pegylated MMP-cleavable imaging probe and an anticancer peptide (buforin IIb).
• Evaluated the system's ability to selectively image cancer tissues and release the therapeutic agent in response to MMP.
• Tested the system in SCC7 tumor-bearing mice to assess in vivo imaging and therapeutic efficacy.

Main Results:

• The IPGO/BF system showed selective fluorescence in tumor tissues.
• Cleavage of the MMP-sensitive peptide triggered imaging and subsequent exposure of the anticancer peptide, enhancing therapeutic function.
• Treated mice demonstrated greater imaging signal-dependent antitumor effects compared to control groups.

Conclusions:

• The developed nanosystem offers a feasible strategy for selective, imaging-dependent sequential activation of anticancer therapy.
• This approach can reduce nonspecific false-positive imaging signals and minimize side effects of anticancer drugs on normal tissues.