Xin Liang

Personalized cancer vaccines show great potential in cancer immunotherapy by inducing an effective and durable antitumor response. However, the limitation of neoantigen identification, low immunogenicity, and weak immune response hamper the development of personalized cancer vaccines. The surgically removed tumor contains tumor antigens specific to the patient, which provides a promising source for personalized cancer vaccines. Here, we utilized the surgically removed tumor to prepare a personalized photothermal vaccine combined with the PD-1 checkpoint blockade antibody to prevent tumor relapse and metastasis. Black phosphorus quantum dot nanovesicles (BPQD-CCNVs) coated with surgically removed tumor cell membrane were prepared and loaded into a thermosensitive hydrogel containing GM-CSF and LPS. The sustained release of GM-CSF from the hypodermic injection of Gel-BPQD-CCNVs effectively recruited dendritic cells to capture tumor antigen. NIR irradiation and LPS stimulated the expansion and activation of DCs, which then traveled to the lymph nodes to present antigen to CD8+ T cells. Moreover, the combination with PD-1 antibody significantly enhanced tumor-specific CD8+ T cell elimination of the surgical residual and lung metastatic tumor. Hence, our work may provide a promising strategy for the clinical development of a personalized cancer vaccine.

Magnetite (iron oxide, Fe3O4) nanoparticles have been widely used for drug delivery and magnetic resonance imaging (MRI). Previous studies have shown that many metal-based nanoparticles including Fe3O4 nanoparticles can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. To investigate the biosafety of Fe3O4 and PLGA-coated Fe3O4 nanoparticles, some experiments related to the mechanism of autophagy induction by these nanoparticles have been investigated. In this study, the results showed that Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticles could be taken up by the cells through cellular endocytosis. Fe3O4 nanoparticles extensively impair lysosomes and lead to the accumulation of LC3-positive autophagosomes, while PLGA-coated Fe3O4 nanoparticles reduce this destructive effect on lysosomes. Moreover, Fe3O4 nanoparticles could also cause mitochondrial damage and ER and Golgi body stresses, which induce autophagy, while PLGA-coated Fe3O4 nanoparticles reduce the destructive effect on these organelles. Thus, the Fe3O4 nanoparticle-induced autophagosome accumulation may be caused by multiple mechanisms. The autophagosome accumulation induced by Fe3O4 was also investigated. The Fe3O4, PLGA-coated Fe3O4, and PLGA nanoparticle-treated mice were sacrificed to evaluate the toxicity of these nanoparticles on the mice. The data showed that Fe3O4 nanoparticle treated mice would lead to the extensive accumulation of autophagosomes in the kidney and spleen in comparison to the PLGA-coated Fe3O4 and PLGA nanoparticles. Our data clarifies the mechanism by which Fe3O4 induces autophagosome accumulation and the mechanism of its toxicity on cell organelles and mice organs. These findings may have an important impact on the clinical application of Fe3O4 based nanoparticles.