Polysarcosine-Functionalized Graphene Oxide Improves Biological Safety and Enhances Chemo-Photothermal Therapy Synergistic Anticancer Effect.

Background: Graphene oxide (GO) has high drug-loading capacity and good photothermal property. However, the limited stability and poor biocompatibility of GO hindered its application as drug delivery carrier for future nanomedicine. Methods: In this study, a new strategy of using chemical conjugation on GO with polypeptide was adopted. A novel Biotin grafted polysarcosine polymers (B-PSar) modified graphene oxide derivative (B-PSar-GO) was successfully synthesized and utilized as a carrier to develop a new drug delivery system for targeted chemo-photothermal cancer therapy. In vitro and in vivo experiments evaluated the system's biosafety and antitumor efficacy. Results: With the B-PSar protection, the B-PSar-GO showed excellent biological safety with the average size of 268.2±8.4 nm. Stability experiments displayed B-PSar-GO was extremely stable. The anti-cancer drug doxorubicin (DOX) was loaded on B-PSar-GO through π-π interactions and hydrophobic interactions, B-PSar-GO@DOX achieved a maximum loading capacity of 25.5%. In addition, B-PSar-GO@DOX exhibited NIR/pH dual-responsive DOX release characteristics, ensuring sustained drug release to tumor tissues triggered by NIR laser irradiation and acidic tumor microenvironment. Based on the excellent photothermal conversion efficiency of GO, B-PSar-GO@DOX showed excellent chemo-photothermal synergistic tumor inhibition both in vitro and in vivo under NIR irradiation. Conclusion: The novel nano-drug delivery system B-PSar-GO@DOX developed in this paper offers a promising platform for chemo-photothermal synergistic cancer treatment.