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. Author manuscript; available in PMC: 2023 Mar 14.
Published in final edited form as: Cancer Cell. 2022 Feb 10;40(3):255–276. doi: 10.1016/j.ccell.2022.01.006

Figure 5. “Indirect” targeting via macropinocytosis inhibitory nanoparticles (MiNP).

Figure 5.

(A) Example targeted “effector” nanoparticles (E-NP) bearing cancer therapeutic cargo and displaying a folate receptor binding ligand. E-NP commonly accumulate within tumor cells at low levels due to high uptake by cells of the mononuclear phagocyte system (MPS).

(B) Indirect targeting strategies provide one solution to this issue via silencing MPS uptake with micropinocytosis inhibitory nanoparticles (MiNP). The macropinocytosis inhibitor Latrunculin A (LatA) is depicted here. LatA is a 16-membered macrolide that depolymerizes actin in the cytoskeleton and blocks the incorporation of actin monomers into actin filaments (LatA-actin complex is displayed from PDB ID: 1ESV). The pre-injection of MiNP results in the safe and transient inhibition of MPS cells that are responsible for scavenging and clearing the majority of administered nanocarriers and biologics. The subsequent administration of E-NPs achieves enhanced accumulation within the TME. Aspects of this figure were adapted from Stack et al., 2021. Nanoscale Horiz. 6, 393–400.