Harnessing the Formation of Natural Killer–Tumor Cell Immunological Synapses for Enhanced Therapeutic Effect in Solid Tumors. Issue 22 (21st April 2020)

• Record Type: Journal Article
• Authors: Im, Sooseok; Jang, Donghyun; Saravanakumar, Gurusamy; Lee, Junseok; Kang, Yeoul; Lee, Yeong Mi; Lee, Jaehyun; Doh, Junsang; Yang, Zung Yoon; Jang, Myoung Ho; Kim, Won Jong
• Is Part Of: Advanced materials. Volume 32:Issue 22(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-04-21
• Subjects: immunological synapses -- NK cells -- pH‐sensitive micelles -- solid tumors -- stimuli‐responsive drug‐delivery systems; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202000020
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: The formation of an immunological synapse (IS) on recognition of a cancer cell is the main mechanism underlying the natural killer (NK)‐cell‐mediated killing of tumor cells. Herein, an integrative strategy for cancer therapy against solid tumors is reported, in which alterations in the cleft of IS, following the secretion of acidic granular content, are utilized as a trigger for the delivery of chemotherapeutic drugs. NK cells are decorated with the IS‐environment‐responsive micellar system to ensure the release of the payload when they attack cancer cells. Using this strategy, the immunological cytotoxic killing effect of NK cells against solid tumors is reinforced with the site‐specific diffusion of chemotherapeutic agents. Harnessing the intrinsic mechanism for the recognition of abnormal cells and the tumor‐homing effect of NK cells limit the adverse systemic effects of chemotherapeutic drugs. This approach may provide a pragmatic platform for the universal and effective utilization of IS formation. Abstract : A reinforced natural killer (ReNK) cell system is designed to release drugs upon the formation of an NK–tumor cell immunological synapse. Degranulation and acidification at the synapse cleft trigger the disassembly of pH‐sensitive polymeric micelles on the surface of the NK cells. Doxorubicin released from ReNK diffuses into the tumor tissue, overcoming the insufficient therapeutic effect due to restricted infiltration of NK cells.