MMP-2 Responsive Peptide Hydrogel-Based Nanoplatform for Multimodal Tumor Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Responsive drug delivery systems offer targeted tumor treatment, minimizing systemic toxicity.
• Matrix metalloproteinases-2 (MMP-2) enzyme-sensitive peptides can be utilized for targeted drug release.
• Multimodal cancer therapy combining photothermal, chemotherapy, and immunotherapy shows promise.

Purpose of the Study:

• To design and construct a MMP-2 responsive multifunctional peptide hydrogel platform (aP/IR@FMKB) for cancer photothermal-chemo-immunotherapy.
• To evaluate the hydrogel's ability to deliver bufalin (BF), IR820, and aPD-L1 in a controlled and targeted manner.
• To assess the therapeutic efficacy of the aP/IR@FMKB hydrogel in a tumor microenvironment.

Main Methods:

• Covalently bound MMP-2 enzyme-sensitive peptide to a tissue-penetrating peptide to create the hydrogel.
• Loaded bufalin (BF) in trimethyl chitosan nanoparticles (TB NPs), along with IR820 and aPD-L1, via self-assembly.
• Evaluated in vitro cytotoxicity, immunogenic cell death (ICD) induction, tumor penetration, retention, and antitumor activity in various tumor models.

Main Results:

• The aP/IR@FMKB hydrogel exhibited excellent photothermal performance and prolonged local retention.
• The system successfully induced ICD, sensitizing PD-L1 blockade and significantly increasing intratumor CD8+ T-cell frequency (3.5-fold in primary, 5.2-fold in distal tumors).
• Demonstrated remarkable efficacy in suppressing primary, distal, and recurrent tumors.

Conclusions:

• The responsive hydrogel effectively modulates the tumor immune microenvironment and is sensitive to PD-1/PD-L1 blockade.
• This innovative hydrogel platform holds significant potential for multimodal cancer therapy.
• The study highlights a promising strategy for enhancing cancer treatment outcomes through targeted drug delivery and immunotherapy.