T Cell Membrane Mimicking Nanoparticles with Bioorthogonal Targeting and Immune Recognition for Enhanced Photothermal Therapy

Abstract

Due to specific immune recognition receptors on the surface of T cells, their membranes are promising mimic nanocarriers for delivering drugs to tumor lesions. However, this single targeting strategy potentially compromises therapy efficacy for tumor targeting due to inter‐ and intra‐heterogeneity of tumors. Azide (N 3 ) or bicyclo [6.1.0] nonyne (BCN) modified unnatural sugars can be successfully incorporated into surface glycans of various tumor cells as artificial receptors, which is expected to overcome the insufficiency of single targeting. Based on this artificial tumor targeting strategy, indocyanine green nanoparticles (INPs) coated with N 3 ‐labeled T cell membrane (N 3 ‐TINPs) are constructed, which can specifically target the natural antigen and BCN artificial receptors on tumors through immune recognition and bioorthogonal chemistry, respectively. The results show that the fluorescence intensity in the tumors of mice treated with N 3 ‐TINPs is 1.5 fold compared with that of the mice treated with unlabeled TINPs. The accumulated N 3 ‐TINPs in the tumor significantly increase the photothermal therapeutic effect without adverse effect. Therefore, this T cell membrane mimicking nanoparticles based bioorthogonal chemistry may provide an alternative artificial targeting strategy for further tumor targeting photothermal therapy.

Nanotechnology for virus treatment

“…Similarly, the neutrophil nanosponges could neutralize a multitude of cytokines such as IL-1β and TNF-α due to the presence of their respective surface receptors. Biomimetic nanosponges can be manipulated using different techniques to bestow additional functionalities [ 313 , 314 , [341] , [342] , [343] ]. RBC nanosponges modified with melittin and oleyloxyethyl phosphorylcholine were able to selectively attract and neutralize phospholipase A2 (PLA2) [ 344 ], an enzyme implicated in autoimmune disorders such as acute pancreatitis [ 345 ].…”

T‐Cell‐Mimicking Nanoparticles for Cancer Immunotherapy

“…We used the EL4 cell line because the EL4 cell line expresses various plasma‐membrane proteins, [ 19 ] as stably as primary T cells do (Figure S1, Supporting Information). For the clinical transition of TCMNPs, a human T lymphocyte cell line [ 20 ] or human primary cytotoxic T lymphocytes [ 21,22 ] could be utilized as an alternative to EL4 cell line for T cell membrane coating. Although the T cell membrane used for TCMNP fabrication was derived from a T cell line (EL4 cell) rather than primary T cells, the risk of tumorigenesis after TCMNP injection in vivo would be low because only the plasma membrane parts without tumorigenic genetic materials were used for TCMNP fabrication.…”

Immunocyte Membrane-Coated Nanoparticles for Cancer Immunotherapy

“…Hence, dual or multi-targeting is a promising approach to tackle either target antigen loss or down-regulation [ 94 ]. Cai et al [ 95 ] employed a dual-targeting strategy based on azide (N 3 )-labeled T-cell membrane-coated nanoparticles to enhance PTT for tumor. In this work, the bicyclononyne (BCN) group as artificial receptors were introduced into the tumor via natural glycometabolic labeling by pretreating the tumor with Ac 4 ManN-BCN group first.…”