Internalization of red blood cell-mimicking hydrogel capsules with pH-triggered shape responses.
We report on naturally inspired hydrogel capsules with pH-induced transitions from discoids to oblate ellipsoids and their interactions with cells. We integrate characteristics of erythrocytes such as discoidal shape, hollow structure, and elasticity with reversible pH-responsiveness of poly(methacrylic acid) (PMAA) to design a new type of drug delivery carrier to be potentially triggered by chemical stimuli in the tumor lesion. The capsules are fabricated from cross-linked PMAA multilayers using sacrificial discoid silicon templates. The degree of capsule shape transition is controlled by the pH-tuned volume change, which in turn is regulated by the capsule wall composition. The (PMAA)15 capsules undergo a dramatic 24-fold volume change, while a moderate 2.3-fold volume variation is observed for more rigid PMAA-(poly(N-vinylpyrrolidone) (PMAA-PVPON)5 capsules when solution pH is varied between 7.4 and 4. Despite that both types of capsules exhibit discoid-to-oblate ellipsoid transitions, a 3-fold greater swelling in radial dimensions is found for one-component systems due to a greater degree of the circular face bulging. We also show that (PMAA-PVPON)5 discoidal capsules interact differently with J774A.1 macrophages, HMVEC endothelial cells, and 4T1 breast cancer cells. The discoidal capsules show 60% lower internalization as compared to spherical capsules. Finally, hydrogel capsules demonstrate a 2-fold decrease in size upon internalization. These capsules represent a unique example of elastic hydrogel discoids capable of pH-induced drastic and reversible variations in aspect ratios. Considering the RBC-mimicking shape, their dimensions, and their capability to undergo pH-triggered intracellular responses, the hydrogel capsules demonstrate considerable potential as novel carriers in shape-regulated transport and cellular uptake.
Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
Veronika
V
Kozlovskaya
Jenolyn F
JF
Alexander
Yun
Y
Wang
Thomas
T
Kuncewicz
Xuewu
X
Liu
Biana
B
Godin
Eugenia
E
Kharlampieva
D000818:Animals; D016880:Anisotropy; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology*; D005456:Fluorescent Dyes / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology / Q000379:methods; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D020100:Hydrogels; D011108:Polymers; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D012825:Silicon