Peptide-Guided System with Programmable Subcellular Translocation for Targeted Therapy and Bypassing Multidrug...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapeutics

Background:

• Nonselectivity and drug resistance are significant challenges in cancer therapy.
• Current strategies for cancer theranostics require simultaneous solutions for these hurdles.

Purpose of the Study:

• To develop a peptide-guided system capable of overcoming cancer nonselectivity and drug resistance.
• To create a dual-targeting peptide-drug conjugate (PDC) for enhanced cancer theranostics.

Main Methods:

• Modular integration of a cancer biomarker-specific peptide, a mitochondria-targeting motif, and a cell toxin.
• Utilizing cell imaging for uptake and intracellular translocation analysis.
• In vivo imaging and tumor inhibition assays to evaluate therapeutic efficacy.

Main Results:

• The dual-targeting PDC demonstrated cancer cell-specific uptake and programmable intracellular translocation.
• The system effectively diverted the drug's toxic effect to mitochondria, bypassing nuclear localization.
• Mechanism investigation revealed a transformed cell damage pathway, beneficial for reversing drug resistance.
• In vivo studies showed targeted tumor accumulation, tumor suppression, and no observed side effects.

Conclusions:

• The developed dual-targeting PDC offers a promising strategy to enhance the therapeutic index of anticancer drugs.
• This tailored transportation route provides a generally applicable approach for overcoming cancer treatment obstacles.
• The PDC system exhibits potential for effective and safe cancer theranostics.