Wen-Xing Zhang,Ze-Lei Zhou,Qi-Yan Lv,Xiejie Song,Junyang Chen,Chang-Bin Niu,Hui-Fang Cui
Cancer starvation/photothermal combined tumor therapy (CST/PTT) has attracted great interest attributed to their mutual compensation and synergistically enhanced effect. However, the very low O2 supply in the tumor microenvironment (TME) greatly limits the CST efficiency of glucose oxidase (GOx). Additionally, the easy degradation in blood circulation and significant off-target effects are big challenges for clinical applications of the GOx-based CST. In this study, a drug delivery system (DDS) with specific tumor-targeted GOx delivery, near-infrared (NIR) light and TME responsive O2 generation, NIR-responsive glucose consumption, high GOx loading, and efficient NIR photothermia was developed. Positively charged AuNRs@MnO2@SiO2 nanoparticles (named AMS+ NPs) were synthesized. GOx was covalently loaded with a high loading ratio of 36.0%. Finally, a thermosensitive biomimetic hybrid membrane composed of a thermosensitive lipid (TSL) membrane, red blood cell membrane (RBCM), and 4T1 cancer cell membrane (CCM) was coated on the NPs through a double-layer strategy. The AMS+-G@TSL@[RBC-CC-TSL]M NPs consumed 32.7 times glucose at 50 °C as that at 37 °C and generated 4.9 times O2 upon NIR laser irradiation. The thermosensitive biomimetic NPs showed an efficient targeting capability to the homotypic 4T1 cancer cells/tumors accompanied by good biocompatibility, macrophage evading capability, high cancer cell cytotoxicity, and excellent antitumor efficacy. The tumor growth inhibition ratio with NIR laser irradiation reached 92.8%. The AMS+-GOx@TSL@[RBC-CC-TSL]M NPs provide a smart, efficient, safe, PTT/CST combined DDS for highly efficient tumor therapy.
Wen-Jie Zheng,Ze-Lei Zhou,Qi-Yan Lv,Xiaojie Song,Wen-Xing Zhang,Hui-Fang Cui
Tumor hypoxia greatly restricts photodynamic therapy (PDT) efficiency. Photothermal therapy (PTT) implemented at high temperatures induces local skin burning and surrounding tissue damage. Herein, an near-infrared (NIR)- and H 2 O 2 -double responsive heat- and O 2 -generating core–shell–shell AuNRs@MnO 2 @SiO 2 nanocarrier with Au nanorods (AuNRs) as core and MnO 2 as sandwiched nanolayer is developed to realize enhanced photodynamic/photothermal combined tumor therapy at mild-hyperthermia temperatures. Coating poly- l -lysine on AuNRs is capable of preventing AuNRs from aggregation and facilitating the on-site growth of MnO 2 . The mesoporous SiO 2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO 2 nanolayer greatly enhances the singlet oxygen ( 1 O 2 ) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O 2 -enhanced PDT endows the AuNRs@MnO 2 @SiO 2 -ICG nanoparticles (NPs) dramatically stronger antitumor effect both in vitro and in vivo. Their tumor growth inhibition ratio (67.6%) is significantly higher than that of AuNRs@SiO 2 -ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO 2 @SiO 2 -ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO 2 @SiO 2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.
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