Figure 5.

Self-assembly of ELP (labeled chimeric polypeptide (CP) in the figure panel) by drug conjugation. a) Attachment of three to six copies of small molecules with log D above 1.5 (shown in red) triggers self-assembly, whereas small molecules with log D less than 1.5 (shown in blue) does not trigger self-assembly. b) Hydrodynamic radius (R_h) (black curve) and transition temperature (T_t) (red curve) of ELP-small molecule conjugates as a function of log D. Below a log D of 1.5, conjugation of molecules does not trigger self-assembly, as the conjugates have an R_h of 6 nm, consistent with ELP unimers. As the log D of conjugate small molecules increase above 1.5, the ELP-conjugate self-assembles into micelles with an R_h of ≈30 nm. The concentration dependence of the T_t also decreases, indicating micelle formation. c) Conjugation of doxorubicin (Dox) to ELP triggers self-assembly into monodisperse micelles with an R_h of 22 nm as seen by freeze fracture scanning electron microscopy. In the C26 colon cancer model, ELP-Dox micelles (CP-Dox) at their MTD outperformed free Dox in reducing tumor growth rate and promoting survival. d) Conjugation of paclitaxel (PTX) to ELPs (labeled CP in the figure panel) drives self-assembly into mono-disperse spherical micelles as seen in the cryo-TEM micrographs. A single dose of ELP-PTX (CP-PTX) micelles outperformed both free PTX and Abraxane in a subcutaneous human prostate tumor model, PC3. All the mice in ELP-PTX group survived beyond 70 days (scale bar = 200 nm). (a-b) Reproduced with permission.^[95] Copyright 2013, John Wiley and Sons. (c) Reproduced with permission.^[96] Copyright 2015, Springer Nature. (d) Reproduced with permission.^[97] Copyright 2009, Springer Nature.