Time-Resolved Small-Angle X-ray Scattering Studies of pH-Induced PMPC–PDPA Diblock Copolymer Self-Assembly

Despite the potential of poly(2-methacryloyloxy ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) diblock copolymer nanoparticles for several biological applications, the exact mechanism of pH-induced self-assembly of the PMPC-PDPA chains into nanoparticles remains unclear, although it has been extensively studied by <i>ex situ</i> transmission electron microscopy. Here, we probe this process using time-resolved small-angle X-ray scattering (TR-SAXS) to gain an understanding of the phenomena that occur on the nanoscale. Modeling the TR-SAXS data indicated that spherical micelles and vesicles were formed at a pH as low as 3, and the spherical micelle and vesicle structures reformed at pH 5.5. At pH ∼5.5, insoluble PMPC₂₅-PDPA₇₀ diblock copolymer precipitation was also observed by SAXS. A huge soluble PMPC₂₅-PDPA₇₀ diblock copolymer reservoir might assist in PMPC₂₅-PDPA₇₀ vesicle construction. Additionally, a potential pathway of vesicle construction by spherical micelle fusion was supported by the SAXS evidence.