Cellular Cyborgs: On the Precipice of a Drug Delivery Revolution Song Ding, Colin P. O'Banion, Joshua G. Welfare, David S. Lawrence  Cell Chemical Biology  Volume 25, Issue 6, Pages 648-658 (June 2018) DOI: 10.1016/j.chembiol.2018.03.003 Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 1 Characteristics of Various Cell Types Employed for Drug Delivery Modification of images purchased from lady_in_red13/Timonina/Designua/Shutterstock.com. Cell Chemical Biology 2018 25, 648-658DOI: (10.1016/j.chembiol.2018.03.003) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 2 Strategies for Intracellular Loading and Retention of Therapeutic Agents in Cellular Vehicles (A and B) Hypotonic conditions generate pores in RBCs that enable otherwise membrane-impermeable compounds to enter the cytoplasm. Membrane-impermeable moieties, including (A) B12 and (B) phosphate are used to retain the appended drug inside the RBC. (C) Introduction (or expression) of the biochemical target of a drug has also been employed to promote intracellular loading of therapeutic agents. Cell Chemical Biology 2018 25, 648-658DOI: (10.1016/j.chembiol.2018.03.003) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 3 Strategies for Surface Loading of Therapeutic Agents on Cellular Vehicles Noncovalent methods have been employed to attach therapeutics to the surface of cells, including (A) lipophilic anchors for membrane insertion, (B) nonspecific electrostatic, hydrogen bonding, and related interactions, and (C) targeted association (e.g., antibody) with specific surface proteins. A variety of covalent methods have been developed to couple therapeutics to the surface of cells, including: (D) modification of surface amines (lysine), sulfhydryls (cysteine), and nonnative functionality, including aldehydes (generated from sugars) and azides (via metabolic introduction). Where ③ indicates drugs or drug-containing nanoparticles. Cell Chemical Biology 2018 25, 648-658DOI: (10.1016/j.chembiol.2018.03.003) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 4 Strategies for Release of Therapeutic Agents from Cellular Vehicles (A) Methods of continuous drug release include the slow hydrolysis of pro-drugs and the ejection of exosome-encapsulated therapeutics. (B) A variety of external commands have been used to trigger the discharge of therapeutics including light-, ultrasound-, and magnetic field-induced thermal release. (C) Cell carriers have been developed that release drugs in response to in vivo signals, including a variety of biomolecules (glucose, hormones, etc.), pH, and changes in cell shape. Cell Chemical Biology 2018 25, 648-658DOI: (10.1016/j.chembiol.2018.03.003) Copyright © 2018 Elsevier Ltd Terms and Conditions