A Bait-and-Hook Hydrogel for Net Tumor Cells to Enhance Chemotherapy and Mitigate Metastatic Dissemination

<b>Background</b>: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, expanding preclinical and clinical evidence indicates that chemotherapy may promote tumor metastasis and cause side effects. <b>Methods</b>: We develop an injectable bait-and-hook hydrogel (BH-gel) for targeted tumor cell eradication, which embedded doxorubicin liposomes as cytotoxic agents and CXCL12 as a chemoattractant to capture and kill tumor cells. The hydrogel backbone was formed through covalent cross-linking between PVA and borax. In vitro, we investigated tumor recruitment and the antitumor effects in A549 cells. In vivo, we explored the anti-metastatic and antitumor activities against lung cancer. <b>Results</b>: BH-gel retained CXCL12 within its three-dimensional porous architecture for gradual release, effectively recruiting tumor cells. In contrast, blank hydrogel failed to achieve this. After encapsulation in BH-gel, the therapeutic efficacy of doxorubicin liposomes for tumor eradication was markedly improved, significantly reducing metastatic tumor presence to near-undetectable levels, while also resulting in notable reductions in cardiotoxicity and hepatotoxicity. Notably, BH-gel adhered well to tissues and exhibited exceptional electrical conductivity, which may be further developed into a real-time tumor monitoring system, facilitating timely therapeutic adjustments. <b>Conclusions</b>: BH-gel utilizes CXCL12 as a bait to recruit and entrap tumor cells in a three-dimensional porous matrix and subsequently kill them with embedded doxorubicin liposomes, thereby tackling the issue of metastatic spread. This bait-and-hook strategy has significant implications for the field of anti-metastasis medicine and shows considerable potential for clinical application.