Biomimetic gene editing system for precise tumor cell reprogramming and augmented tumor therapy.

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Cancer Research

Background:

• Abnormal hypoxia-inducible factor-1 alpha (HIF-1α) levels correlate with cancer metastasis and treatment resistance.
• CRISPR-Cas9 gene editing offers precise gene disruption but faces challenges in safe and efficient in vivo delivery.

Purpose of the Study:

• To develop a cell membrane biomimetic core-shell system for light-controllable, in vivo CRISPR-Cas9 gene editing.
• To enhance anti-metastatic effects and improve chemotherapeutic efficacy in cancer treatment.

Main Methods:

• Development of a core-shell system with protamine and calcium ions for CRISPR-Cas9/sgRNA plasmid (pCas9) loading and transfection.
• Camouflage with cell membrane and modification with AS1411 aptamers for tumor targeting.
• Incorporation of photosensitizers for light-induced reactive oxygen species production, lysosomal escape, and pCas9 release.

Main Results:

• The biomimetic system, upon laser irradiation, reprogrammed H1299 cancer cells, reducing VEGF and Vimentin expression.
• Demonstrated enhanced anti-metastatic effects in vitro.
• Genetic disruption of HIF-1α using this system augmented the in vivo efficacy of paclitaxel chemotherapy.

Conclusions:

• The developed membrane-camouflaged system combined with light augmentation provides a potential solution for in vivo CRISPR-Cas9 delivery.
• This approach offers a feasible strategy for enhancing cancer therapy by targeting HIF-1α and improving chemotherapeutic outcomes.