Multifunctional Hypoxia-Involved Gene Silencing Nanoplatform for Sensitizing Photochemotherapy

The integration of combinational photochemotherapy could achieve a promoted therapeutic performance by eliminating the frustrating side effects of each constitute, yet it is still confronted with severe therapeutic resistances that are associated with tumor hypoxia. Herein, we designed a multifunctional gene-therapy-promoted photochemotherapy strategy for specifically alleviating the hypoxia-associated therapeutic resistance. The pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (CDHNs) facilitated the effective delivery of therapeutic agents (chlorin e6 (Ce6), doxorubicin (DOX), and HIF-1 alpha siRNA) into the tumor for relieving specifically photochemotherapy resistance via sequential activation manners under the guidance of fluorescence imaging. The present all-in-one compact CDHNs system provides a smart and versatile multiply gained therapeutic strategy to activate the specific cellular pathways and is anticipated to boost future cancer diagnosis and post-treatment.