Xiaoqi Sun

Abstract Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO 2 ) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO 2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO 2 -PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H 2 O 2 to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment.

Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membranes modified by mannose. Poly(d,l-lactide- co-glycolide) nanoparticles are first loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification with mannose moiety (NP-R@M-M), the obtained nanovaccine shows enhanced uptake by antigen presenting cells such as dendritic cells, which would then be stimulated to the maturation status to trigger antitumor immune responses. With great efficacy to delay tumor development as a prevention vaccine, vaccination with such NP-R@M-M in combination with checkpoint-blockade therapy further demonstrates outstanding therapeutic efficacy to treat established tumors. Therefore, our work presents an innovative way to fabricate cancer nanovaccines, which in principle may be applied for a wide range of tumor types.

Significance Hydrogen peroxide is closely associated with many important physiological and pathological events. Herein, we develop a liposomal nanoprobe for in vivo H 2 O 2 -responsive chromogenic assay, which is highly specific and sensitive to H 2 O 2 . Using such a nanoprobe, photoacoustic imaging of H 2 O 2 -related inflammation processes in mice induced by either LPS or bacteria is realized. Meanwhile, such a nanoprobe, by reacting with endogenous H 2 O 2 produced by tumor cells, allows sensitive photoacoustic imaging of early-stage small tumors and orthotopic brain glioma and even enables accurate differentiation of metastatic sentinel lymph nodes from nonmetastatic ones. Furthermore, owing to its H 2 O 2 -responsive near-infrared absorbance, selective photothermal ablation of tumors is also achieved, illustrating the promise of using this nanoproble for tumor theranostics with great specificity.

A novel type of bio-nanoreactor with catalase loaded inside TaOx hollow nanoshells is fabricated via a mild one-step method. Such bio-nanoreactors could efficiently improve the tumor oxygenation by supplying oxygen via decomposition of endogenic H2O2 in a tumor microenvironment, and thus synergistically enhance the efficacy of cancer radiotherapy by both depositing radiation energy within the tumor and overcoming hypoxia-induced radiotherapy resistance. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.