Few-Shot Identification of Active Therapeutic Peptide Networking with Gradient Dynamics against Cancer

Area of Science:

• Biomaterials Science
• Oncology
• Drug Delivery

Background:

• Osteosarcoma treatment faces challenges with current chemotherapy limitations.
• Anticancer peptides offer potential but suffer from degradation and poor tumor selectivity.
• Developing targeted and effective cancer therapies is a critical unmet need.

Purpose of the Study:

• To engineer a novel peptide-drug conjugate for enhanced osteosarcoma treatment.
• To develop an injectable hydrogel system for controlled drug release and improved therapeutic outcomes.
• To evaluate the safety and efficacy of the novel therapeutic platform in preclinical models.

Main Methods:

• A few-shot peptide screening strategy identified RT2 and E16 peptides.
• Engineered a fusion peptide E16-RT2 (ER) with enhanced tumor-selective cytotoxicity.
• Developed an injectable hydrogel encapsulating doxorubicin with gradient release dynamics.

Main Results:

• The engineered ER peptide demonstrated 175% enhanced tumor-selective cytotoxicity and cancer membrane targeting.
• The hydrogel system provided sustained therapeutic efficacy for over 9 days.
• No systemic or organ toxicity was observed in murine models.

Conclusions:

• The ER peptide-hydrogel platform effectively overcomes limitations of conventional chemotherapy for osteosarcoma.
• The dual functionality of ER peptides and smart biomaterials offers a clinically translatable approach.
• The demonstrated safety-efficacy profile positions this platform as a viable strategy for cancer treatment.