Natural Science Foundation of Fujian Province of China; Xiamen Science and Technology Bureau of ChinaBackground: Polybutylcyanoacrylate (PBCA) nanoparticles coated with polysorbate-80 have been extensively proposed for delivering drugs into the animal brain and have shown great potential for therapeutic applications. In this study, we made an attempt to deliver the chemotherapeutic drug, temozolomide, into the brain by using PBCA nanoparticles. The physicochemical characteristics, in vitro release, and brain targeting ability of the drug-loaded nanoparticles were investigated. Results: Our results show that a significantly higher concentration of temozolomide in the form of polysorbate-80-coated PBCA nanoparticles was observed in the brain (P < 0.05) in comparison with the free drug. Conclusion: This study indicates that polysorbate-80 coated PBCA nanoparticles could be a feasible carrier for temozolomide delivery to the brain. It is anticipated that the developed formulation may improve on targeted therapy for malignant brain tumors in the future

Background: Gene transfer using a nanoparticle vector is a promising new approach for the safe delivery of therapeutic genes in human disease. The Tat peptide-decorated gelatinsiloxane (Tat-GS) nanoparticle has been demonstrated to be biocompatible as a vector, and to have enhanced gene transfection efficiency compared with the commercial reagent. This study investigated whether intracisternal administration of Tat-GS nanoparticles carrying the calcitonin gene-related peptide (CGRP) gene can attenuate cerebral vasospasm and improve neurological outcomes in a rat model of subarachnoid hemorrhage. Method: A series of gelatin-siloxane nanoparticles with controlled size and surface charge was synthesized by a two-step sol-gel process, and then modified with the Tat peptide. The efficiency of Tat-GS nanoparticle-mediated gene transfer of pLXSN-CGRP was investigated in vitro using brain capillary endothelial cells and in vivo using a double-hemorrhage rat model. For in vivo analysis, we delivered Tat-GS nanoparticles encapsulating pLXSN-CGRP intracisternally using a double-hemorrhage rat model. Results: In vitro, Tat-GS nanoparticles encapsulating pLXSN-CGRP showed 1.71 times higher sustained CGRP expression in endothelial cells than gelatin-siloxane nanoparticles encapsulating pLXSN-CGRP, and 6.92 times higher CGRP expression than naked pLXSN-CGRP. However, there were no significant differences in pLXSN-CGRP entrapment efficiency and cellular uptake between the Tat-GS nanoparticles and gelatin-siloxane nanoparticles. On day 7 of the in vivo experiment, the data indicated better neurological outcomes and reduced vasospasm in the subarachnoid hemorrhage group that received Tat-GS nanoparticles encapsulating pLXSN-CGRP than in the group receiving Tat-GS nanoparticles encapsulating pLXSN alone because of enhanced vasodilatory CGRP expression in cerebrospinal fluid. Conclusion: Overexpression of CGRP attenuated vasospasm and improved neurological outcomes in an experimental rat model of subarachnoid hemorrhage. Tat-GS nanoparticlemediated CGRP gene delivery could be an innovative strategy for treatment of cerebral vasospasm after subarachnoid hemorrhage.

Herein, a tumor microenvironment (TME)‐responsive mimovirus vesicle (MVV) is engineered to deliver azide motifs (–N3) via the membrane fusion mechanism for cancer diagnosis. As a pH‐responsive functional protein, the spike vesicular stomatitis virus G‐protein (VSVG) is genetically immobilized on surface of cell membrane vesicles. By virtue of the low‐pH activated fusogenic peculiarity of VSVG, the –N3 groups, which are also presented on MVVs via metabolic engineering, can be directly anchored onto the target cells, thus reducing tumor heterogeneity and serving as the bait to amplify the tumor targeting of dibenzocyclooctyne‐modified diagnostic moieties. The potential diagnostic capability of such design is successfully confirmed in three different murine tumor models. Featuring excellent pH‐sensitive fusogenic traits, the developed MVVs show great responsiveness to the slightly acidic TME of solid tumors, providing a universal platform in overcoming tumor heterogeneity for precise cancer diagnosis.

Introduction Sonodynamic therapy (SDT) has good targeting and non-invasive advantages in the treatment of solid cancers, and checkpoint blockade immunotherapy is also a promising treatment to cure cancer. However, their antitumor effects are not sufficient due to some inherent factors. Some studies that combined SDT with immunotherapy or nanoparticles have managed to enhance its efficiency to treat cancers. Methods In this work, an effective therapeutic strategy that can potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1) is developed by the use of cascade immuno-sonodynamic therapy (immuno-SDT). Titanium dioxide (TiO 2 ), a nanostructured agent for SDT, sonosensitizer Chlorin e6 (Ce6), and immunological adjuvant CpG oligonucleotide (CpG ODN), are used to construct a multifunctional nanosonosensitizer (TiO 2 -Ce6-CpG). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of TiO 2 -Ce6-CpG under ultrasound (US) treatment. Results The characterization tests showed that the nanosonosensitizers are polycrystalline structure with homogeneous sizes, resulting in a good drug loading efficiency. The innovative nanosonosensitizers (TiO 2 -Ce6-CpG) can not only effectively inhibit tumor growth but also stimulate the immune system to activate the adaptive immune responses, using the TiO 2 -Ce6 to augment SDT and the immune adjuvant CpG to enhance the immune response. After combined with the aPD-L1, the synergistic effect could not only efficiently inhibit the primary tumor growth but also lead to an inhibition of the non-irradiated pre-existing distant tumors by inducing a strong tumor-specific immune response. Conclusion In this study, we present an effective strategy for tumor treatment by combining nanosonosensitizer-augmented SDT and aPD-L1 checkpoint blockade. This work provides a promising strategy and offers a new vision for treating malignant tumors.

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