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Antibody-activated Trans-endothelial Delivery of Mesoporous Organosilica Nanomedicine Augments Tumor Extravasation and Anti-cancer Immunotherapy by Huang, Tinglei (author);Li, Shuang (author);Fang, Jianchen (author);Li, Fuli (author);Tu, Shuiping (author) is a Engineering article available to read on EtoBox.

What is Antibody-activated Trans-endothelial Delivery of Mesoporous Organosilica Nanomedicine Augments Tumor Extravasation and Anti-cancer Immunotherapy about?

Tumor vasculature constitutes a formidable hurdle for the efficient delivery of cancer nanomedicine into tumors. The leverage of passive pathway through inter-endothelial gaps in tumor blood vessels might account for limited extravasation of nanomedicine into tumor microenvironment (TME). Herein, Annexin A1 antibody-installed mesoporous organosilica nanoplatforms carrying immunotherapeutics of anti-PD-L1 antibody (aPD-L1) and Indoximod are developed to target at caveolar Annexin-A1 protein of luminal endothelial cells and to trigger the active __trans__-endothelial transcytosis of nanomedicine mediated by caveolae. Such strategy enables rapid nanomedicine extravasation across tumor endothelium and relatively extensive accumulation in tumor interstitium. aPD-L1 and Indoximod release from aPD/IND@MON-aANN in a reduction-responsive manner and synergistically facilitate the intratumoral infiltration of cytotoxic T lymphocytes and reverse the immunosuppressive TME, thus demonstrating substantial anti-tumor efficacy in subcutaneous 4T1 breast tumors and remarkable anti-metastatic capacity to extend the survival of 4T1 tumor metastasis model. Moreover, aPD/IND@MON-aANN nanomedicine also e

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Author

Huang, Tinglei (author);Li, Shuang (author);Fang, Jianchen (author);Li, Fuli (author);Tu, Shuiping (author)

Publisher

Elsevier BV

Published

2021

Language

EN

Field

Engineering (Physical Sciences)