Internalization of red blood cell-mimicking hydrogel capsules with pH-triggered shape responses.

Abstract

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.

• Authors: Veronika Kozlovskaya, Jenolyn F Alexander, Yun Wang, Thomas Kuncewicz, Xuewu Liu, Biana Godin, Eugenia Kharlampieva
• Journal: ACS nano (ACS Nano) Vol. 8 Issue 6 Pg. 5725-37 (Jun 24 2014) ISSN: 1936-086X [Electronic] United States
• PMID: 24848786 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cross-Linking Reagents
• Fluorescent Dyes
• Hydrogels
• Polymers
• Polymethacrylic Acids
• polymethacrylic acid
• Silicon

Topics

• Animals
• Anisotropy
• Cell Line, Tumor
• Cross-Linking Reagents (chemistry)
• Drug Delivery Systems
• Endocytosis
• Endothelial Cells (cytology)
• Erythrocytes (cytology)
• Fluorescent Dyes (chemistry)
• Hep G2 Cells
• Humans
• Hydrogels (chemistry)
• Hydrogen-Ion Concentration
• Macrophages (cytology, drug effects)
• Materials Testing
• Mice
• Microscopy, Confocal
• Microscopy, Electron, Scanning
• Nanotechnology (methods)
• Polymers (chemistry)
• Polymethacrylic Acids (chemistry)
• Silicon (chemistry)
• Spectroscopy, Fourier Transform Infrared