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. 2022 May 23;14(5):1109. doi: 10.3390/pharmaceutics14051109

Figure 3.

Figure 3

Mammalian cells for targeted drug delivery. (A). RBC hitchhiking (RH) drug delivery system. (Aa) Procedural steps of RH. NPs were first adsorbed onto the RBCs ex vivo. The RBC–NP complexes were then injected intravenously (IV) or intra-arterially (IA). Then, RH transferred NPs to the capillaries of the first downstream organ. (Ab) SEM images of polystyrene NPs (PS-NPs) and nanogels attached to the surface of murine RBCs [100]. NPs were mixed with RBCs in vitro. Scale bars = 1 μm. (B). M2-like tumor-associated macrophage (TAM)-targeted NPs. (Ba) Composition and structure of a self-assembled micelleplex. The amphiphilic diblock copolymers self-assembled into M2-targeting micelles with therapeutic agents. (Bb) TEM images of a micelleplex at pH 7.4 and pH 6.8. At pH 6.8, the size of the micelleplex decreased due to the removal of the sheddable PEG corona. (Bc) Schematic illustration of PEG-sheddable nanodrug targeting M2-like TAMs for tumor immunotherapy [102]. The pH-sensitive nanodrug with M2-targeting peptide (M2pep) was coated with a sheddable PEG corona. It was stable at pH 7.4 but cleavable in the acidic tumor microenvironment (TME) for active M2 targeting. A STAT6 inhibitor, AS1517499 (AS), and IKKβ siRNA were exposed for M2-to-M1 transpolarization for cancer immunotherapy. (C). Confocal micrographs of cellular backpacks attached to the surface of leukocytes (nucleus, blue; membrane, green; backpack, red) [103]. (D). Schematic illustration of neutrophil-mediated delivery of NPs to inflammatory tumor tissues induced by photosensitization (PS) [104]. Firstly, anti-CD11b antibody-coated NPs (NPs-CD11b) were constructed via biotin–neutravidin binding. Then, neutrophils were activated after tumor PS treatment and the intravenously injected NPs-CD11b were internalized by active neutrophils. Finally, NP-laden neutrophils infiltrated the tumor for drug delivery. (Image (B) is reprinted with permission from [102] (Copyright © 2020 American Chemical Society). Image (D) is reproduced with permission from [104] (Copyright © 2017 John Wiley & Sons, Inc.).