Supramolecular Copolymer Micelles Based on the Complementary Multiple Hydrogen Bonds of Nucleobases for Drug Delivery

Abstract

Novel supramolecular copolymer micelles with stimuli-responsive abilities were successfully prepared through the complementary multiple hydrogen bonds of nucleobases and then applied for rapid intracellular release of drugs. First, both adenine-terminated poly(ε-caprolactone) (PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U) were synthesized. The supramolecular amphiphilic block copolymers (PCL-A:U-PEG) were formed based on multiple hydrogen bonding interactions between PCL-A and PEG-U. The micelles self-assembled from PCL-A:U-PEG were sufficiently stable in water but prone to fast aggregation in acidic condition due to the dynamic and sensitive nature of noncovalent interactions. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against NIH/3T3 normal cells. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these supramolecular copolymer micelles. In vitro release studies demonstrated that the release of DOX from micelles was significantly faster at mildly acid pH of 5.0 compared to physiological pH. MTT assay against HeLa cancer cells showed DOX-loaded micelles had high anticancer efficacy. Hence, these supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases are very promising candidates for rapid controlled release of drugs.

Thymine- and Adenine-Functionalized Polystyrene Form Self-Assembled Structures through Multiple Complementary Hydrogen Bonds

“…225-300 nm) for PVBT/PVBA = 30/70, 50/50 and 70/30. In addition, multiple complementary hydrogen bonds are sensitive to the variation of environments, such as temperature and solvents, which will be discussed in our further study [52][53][54]. …”

Well‐defined poly(oxazoline)‐b‐poly(acrylate) amphiphilic copolymers: From synthesis by polymer–polymer coupling to self‐organization in water

“…This property was employed for the encapsulation of chemicals using polymeric drug carriers, 3 as well as for the synthesis of membranes, 4 for instance. Many routes led the synthesis of amphiphilic copolymers using sequential polymerization of CROP and CRP 5 and especially CROP and RITP.…”

Temperature and pH dual‐sensitive polyaspartamide derivatives for antitumor drug delivery

“…This is consistent with observations that the triggering mechanisms for most particulate carriers occur in the endosome and release the drugs into the cytoplasm. 43 The red and green fluorescence were not overlay completely, which indicated that some DOX was successfully released inside the cells from the polymeric micelles (Fig. 7, Line 4).…”