ABSTRACT
Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.
Subject(s)
Delayed-Action Preparations , Hydrogels , Lymph Nodes , Memory T Cells , Programmed Cell Death 1 Receptor , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/immunology , Mice , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Memory T Cells/drug effects , Memory T Cells/immunology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Delayed-Action Preparations/pharmacokinetics , Tumor Microenvironment/drug effects , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Immunotherapy/methods , Female , Mice, Inbred C57BL , HumansABSTRACT
Hot-melt extrusion (HME) is mainly used to enhance the dissolution rate and bioavailability of poorly water soluble drugs. It has many advantages, such as simple process, continuous operation, high efficiency, on-line monitoring and so on. HME provides an innovative approach, which has been concerned by pharmaceutical workers, for preparation of solid dispersion abroad. This article reviews recent advances on preparation of solid dispersion by HME in preparation processing, carrier materials and quality evaluation in order to further promote and apply HME in preparation of solid dispersion.
