Hydrogel enhances CRISPR-mediated tumour targeting

“The strategy of combining YB-1 gene editing and intratumoral injection enhanced the therapeutic effect of doxorubicin while reducing side effects”Li et al.

In contrast, in situ hydrogels offer sustained release, biocompatibility, and tumour-specific retention. The authors specifically targeted Y-box binding protein 1 (YB-1), a known driver of melanoma proliferation and chemoresistance, using Cas9 RNP complexes. Co-delivery with the chemotherapeutic doxorubicin was intended to synergise the effects of gene editing and cytotoxicity.

“The strategy of combining YB-1 gene editing and intratumoral injection enhanced the therapeutic effect of doxorubicin while reducing side effects,” the authors note in their paper.

Three hydrogels were engineered with distinct surface charges—neutral (Nuh), negative (Ngh), and positive (Psh)—using poloxamer polymers. The Psh hydrogel, modified with synthetic polyamines, showed the highest encapsulation efficiency (91%) and slower release kinetics. In vitro, Psh achieved greater cellular uptake and editing efficiency than other formulations or standard transfection reagents. The Psh@DOX@RNP hydrogel induced apoptosis and significantly inhibited melanoma cell proliferation, achieving a YB-1 indel rate of 53% in B16F10 cells. Similar performance was observed in a GFP-reporter assay using human cells.

“Our gel formulation and delivery strategy show significant benefits in blocking melanoma and could offer novel approaches for other surface tumours of the body”Li et al.

The authors conclude that their polyamine-modified hydrogel facilitates efficient co-delivery of gene-editing agents and chemotherapeutics, enhancing tumour localisation and gene disruption while minimising systemic exposure. The combination of local administration, sustained release, and positive surface charge appears to be key to achieving efficient genome editing and therapeutic synergy.

This approach holds promise not only for melanoma but potentially for other solid tumours accessible to local injection. However, the authors acknowledge that further studies are needed to confirm safety in human models and evaluate efficacy in metastatic settings:

“Our gel formulation and delivery strategy show significant benefits in blocking melanoma and could offer novel approaches for other surface tumours of the body.”

The study was conducted by Meng Li, Songli Zhou, Suqin Zhang and colleagues at Hubei University and Tongji Hospital, Huazhong University of Science & Technology. It was published in the Journal of Nanobiotechnology on 13 June 2025.