Perpustakaan Digital ITB

The combination of chemotherapeutic agents withimmune stimulating agents for treating degenerative diseases, calledchemoimmunotherapy, has emerged as a promising cancer treatmentmodality. Despite the tremendous potential, chemoimmunotherapy bythe combination of drugs and immune stimulators often suffers becauseof the lack of controlled delivery nanostructures in the microenviron-ment. To this end, we show that by using pH-responsive smartnanocubes (NCs), cancer cells and tumor-associated immune cells canbe precisely targeted with a chemotherapeutic agent (doxorubicin,DOX) and immune stimulating agent (plasmid ovalbumin, pOVA) forenhanced chemoimmunotherapy. The pH-responsive smart NCsprotect payloads from nuclease degradation and avoid renal clearanceand undergo supersensitive structural change at the extracellular tumorregions that mediate efficient release. Concurrent release of pOVAvaccines encoding tumor-specific antigen laden with polyplexes were loaded on tumor-associated immune cells and produceantigen-specific humoral immune response, whereas DOX enables effective infiltration into the cancer cells and is involved inthe eradication of tumor tissues. The amount of anti-OVA IgG1 antibody produced by the intravenous administration of NCformulation was similar to that of free OVA formulation. Importantly, the combined delivery of pDNA and DOX using NCsshowed significantly enhanced antitumor efficacy in B16/OVA melanoma tumor xenografts, which remarkably outperforms themonotherapy counterparts. These results suggest that pH-responsive smart NCs laden with pDNA and DOX provide apromising nanostructure for chemoimmunotherapy that simultaneously involves cancer cell killing and stimulates antigen-specific immune response to prevent cancer recurrence.