Cancers, originating from gene mutations in a single cell, is hardly detectable until it is beyond control. Challenged by the sensitive, selective and accurate diagnosis and therapy, smart and robust molecular probes capable of discriminating cancer-related molecular signatures in living biosystems are urgently desired.
With the respect to the effectiveness of chemical tools for cancer targeting, a specific peptide AP2H towards a tumor-related protein lysosomal protein transmembrane 4 beta (LAPTM4B) was rationally designed and efficiently evolved. Capable of discriminating LAPTM4B and responding to tumor acidosis, AP2H was successfully utilized as the targeting vehicle for the fabrication of multifunctional bioprobes for tumor treatments. The incorporation of an aggregation-induced emission fluorophore greatly facilitated the real-time tracing and subcellular localization of the target protein in living cells with very high signal-to-noise ratio. Dual-functional peptide probes were also tailored for image-guided photodynamic ablation of cancer cells. Notably, the cell damage effect of the targeted 1O2 generation system is tunable according to the expression level of LAPTM4B protein and thus the progression status of tumors. Taking advantage of the abundant chemistries of peptide conjugates, a peptide-based prodrug was further developed. The integration of the tumor-specific peptide, doxorubicin and a pH-sensitive bridge fulfilled targeted drug delivery and in situ activatable drug release in cancer cells. Our peptide-guided systems provides a promising platform for the design of more sensitive and accurate theranostic approaches for broad-spectrum cancer treatment.