Doxorubicin encapsulated clicked gold nanoparticle clusters exhibiting tumor-specific disassembly for enhanced tumor localization and computerized tomographic imaging

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Abstract

Gold nanoparticles (AuNPs) and matrix metalloproteinase (MMP)-2 cleavable peptides are clicked into gold nanoparticle clusters (AuNCs) for enhanced drug localization and micro computerized tomography (μCT) theranostic of tumors. AuNPs are co-functionalized with doxorubicin (DOX) and an azide-terminated polymer (DOX/N3@AuNPs), and the DOX/N3@AuNPs are associated into DOX@AuNCs in the presence of an alkyne-terminated MMP-2 cleavable peptide (alkyne-peptide-alkyne; APA) by click chemistry. MMP-2-dependent dissociation shows that DOX@AuNCs are highly sensitive to the MMP-2 and are almost completed digested into single nanoparticles. DOX liberation shows that > 75% of the conjugated DOX is bursted out from the digested DOX@AuNCs while < 20% of DOX is released from the integrate DOX@AuNCs within 3 h in acidic conditions, suggesting that DOX is only liberated from dissociated DOX@AuNCs in acidic conditions. In vivo study shows that DOX@AuNCs accumulate in tumor ˜ 150 times higher than DOX/N3@AuNPs do and efficiently suppress tumor growth. Mice administered with AuNCs shows clearer μCT images of tumors. Thus, DOX@AuNCs are expected promising carriers for both anticancer therapy and tumor imaging.

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