Layered-Responsive Multivalent Tetrahedral DNA Framework-Decorated CRISPR-Cas12a Nanocapsule Enables Precise and...

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapy

Background:

• Conventional chemotherapy faces challenges in selective tumor targeting and exhibits high toxicity.
• Developing advanced drug delivery systems is crucial for improving cancer treatment efficacy and reducing side effects.

Purpose of the Study:

• To develop a self-controlled, triple-locked cascade tumor therapy nanocapsule (Tatna) for efficient and targeted cancer treatment.
• To integrate DNA nanostructures with CRISPR-12a technology for precise drug delivery and enhanced therapeutic outcomes.

Main Methods:

• Tatna combines DNA tetrahedrons (DTs), Cas12a/crRNA ribonucleoprotein (Cas12a RNP), and doxorubicin (DOX) within a pH-responsive PLGA nanocapsule.
• A nucleolin-targeting aptamer facilitates selective tumor cell internalization.
• Cas12a RNP activation by APE1 mRNA triggers drug release and apoptosis induction.

Main Results:

• Tatna demonstrated selective tumor targeting and efficient internalization into cancer cells.
• The nanocapsule provided controlled release of DOX and Cas12a in the acidic tumor microenvironment.
• The system effectively induced apoptosis in tumor cells, enhancing therapeutic efficacy.

Conclusions:

• Tatna represents a programmable, tumor-specific delivery system for advanced cancer therapy.
• This multifunctional nanocapsule enhances chemotherapy efficacy while minimizing off-target toxicity.
• The developed system holds promise for precision medicine and personalized cancer treatment strategies.