Biomimetic drug delivery systems offer new opportunities to mimic biological components for enhancing tumor targeting efficiency and promoting therapeutic efficacy. Therefore, in this study, the platelet exosomes and photothermal sensitive liposomes were coalesced and incorporated glucose oxidase (GOx, G) and ferric ammonium (FAC, F) to constitute a laser controlled nanosystem (FG@PEL). Results confirmed that FG@PEL possessed two cascade therapeutic strategies. As the first cascade therapeutic strategy, FG@PEL had achieved cascade targeting effect due to the inheritance of biological property of platelet exosomes to adhere cancer cells and respond on the vascular damage triggered by photothermal effect. Subsequently, GOx was used to oxidize glucose to produce hydrogen peroxide which could be catalyzed by FAC to realize cascade reaction for enhancing chemodynamic therapy (CDT). Meanwhile, photothermal effect could accelerate the reaction rate to further improve the therapeutic effect by producing more hydroxyl radicals. So significant therapeutic effect could be acquired through the synergistic modality of FG@PEL, and the mechanism of mutual promotion among different treatment was also clarified. Hence, this research may provide a promising strategy for curative tumor therapy.

Despite widespread researches engaging in optimizing the efficacy of PDT, the exacerbated hypoxia phenotype in the tumor tissue after PDT has always been neglected. Moreover, the ramifications of aggravated post-PDT hypoxia for tumor microenvironment (TME) have only been poorly investigated. Herein, we report a dual cascade oxygenation strategy with primary oxygenating to promote PDT and re-oxygenation to ameliorate post-PDT hypoxia. In this strategy, nanocomplex RDV@CP@Ce6 was synthesized, which consisted of red blood cell-derived vesicles (RDV) as the outer shell and CAT-PCL nano assembly encapsulating with Ce6 as the inner core. Our results showed that RDV@CP@Ce6 amplified the PDT treatment through the first oxygenation and relieved tumor hypoxia by the second reoxygenation following PDT. On the other hand, the dual cascade oxygenation strategy also could effectively unleash the suppression onto the tumor immune microenvironment, which could further constrain tumor development and metastasis. In addition, RDV@CP@Ce6 also exhibited excellent biocompatibility and superior stability in vivo. This dual cascade oxygenation strategy may provide a promising and pragmatic platform for clinical applications. (c) 2021 Elsevier Ltd. All rights reserved.

Granzyme B (GrB) is a pivotal killer factor in immunotherapy whose application is limited by hyposensitivity and unsatisfactory cellular uptake by tumor cells. In this study, it was proved that SerpinB9 (Sb9) downregulation can enhance the GrB susceptibility of tumor cells. Moreover, a nanocarrier fused with M1 macrophage exosomes (M1 Exo) and photothermal sensitive liposomes was constructed to efficiently transport GrB and siRNA of Sb9 to the cells. The nanocarrier is characterized by cascade tumor targeting acquired by photothermal effect-triggered increased expression of vascular cell adhesion molecule-1 (VCAM-1) in tumor tissue. Furthermore, the innate cytokines in M1 Exo are capable of regulating the tumor microenvironment by repolarizing M2 macrophages to the M1 type. Collectively, the multifunctional nanoplatform (S+G@ELP) enhances the lethality of GrB to tumor cells, activates a widespread immune response uniting with photothermal therapy (PTT), restrains the tumor progression and metastasis effectively, which is expected to provide new insights into GrB-based combinational tumor therapy.

The major obstacles for tumor vaccine to be surmounted are the lack of versatile property and immunity-inducing effectiveness. Induced pluripotent stem cells (iPSCs) expressed various antigens the same as multiple types of tumors, providing a promising source of wide-spectrum cancer vaccines. The damaged erythrocyte membrane entrapped by spleen could be developed as antigen deliverer for enhancing acquired immunity. Here, the modified lipid materials were used to dilate erythrocyte membrane to fabricate coalescent nanovector, which not only preserved the biological characteristics of erythrocyte membrane but also remedied the defect of insufficient drug loading capacity. After wrapping iPSC protein, the nanovaccine iPSC@RBC-Mlipo exhibited obvious splenic accumulation, systemic specific antitumor immunity evocation, and effective tumor expansion and metastasis inhibition in mice. Hence, our research may provide a prospective strategy of efficient tumor vaccine for clinical practice.