Synergistic Anticancer Activity of Photo- and Chemoresponsive Nanoformulation Based on Polylysine-Functionalized Graphene

Multimodal therapeutic agents based on nanomaterials for cancer combination therapy have attracted increasing attention. In this report, a novel photo- and chemoactive nanohybrid was fabricated by assembling photosensitizer Zn(II)-phthalocyanine (ZnPc) and anticancer drug doxorubicin (DOX) on the biocompatible poly-l-lysine (PLL)-grafted graphene (G-PLL). This nanocomplex of G-PLL/DOX/ZnPc showed excellent physiochemical properties, including high solubility and stability in biological solutions, high drug loading efficiency, pH-triggered drug release, and ability to generalize (1)O2 under light excitation. Compared to free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular uptake. In particular, G-PLL/DOX/ZnPc elicited a remarkable synergistic anticancer activity owing to combined photodynamic and chemotherapeutic effects. The combination dose reduction indexes revealed that combining DOX with ZnPc provided strong synergistic effects (combination index < 0.1) against three cancer cell lines tested (HeLa, MCF-7, and B16). Thus, this study demonstrates programmable dual-modality therapy exemplified by G-PLL/DOX/ZnPc to synergistically treat cancers.