No abstract

Reduction-responsive biodegradable micelles were developed from disulfide-linked dextran-b-poly(epsilon-caprolactone) diblock copolymer (Dex-SS-PCL) and applied for triggered release of doxorubicin (DOX) in vitro and inside cells. Dex-SS-PCL was readily synthesized by thiol-disulfide exchange reaction between dextran orthopyridyl disulfide (Dex-SS-py, 6000 Da) and mercapto PCL (PCL-SH, 3100 Da). Dynamic light scattering (DLS) measurements showed that Dex-SS-PCL yielded micelles with an average size of about 60 nm and a low polydispersity index (PDI 0.1-0.2) in PB (50 mM, pH 7.4). Interestingly, these micelles formed large aggregates rapidly in response to 10 mM dithiothreitol (DTT), most likely due to shedding of the dextran shells through reductive cleavage of the intermediate disulfide bonds. DOX could be efficiently loaded into the micelles with a drug loading efficiency of about 70%. Notably, the in vitro release studies revealed that Dex-SS-PCL micelles released DOX quantitatively in 10 h under a reductive environment, mimicking that of the intracellular compartments such as cytosol and the cell nucleus, whereas only about 27% DOX was released from reduction insensitive Dex-PCL micelles in 11.5 h under otherwise the same conditions and about 20% DOX released from Dex-SS-PCL micelles in 20 h under the nonreductive conditions. The cell experiments using fluorescence microscopy and confocal laser scanning microscopy (CLSM) showed clearly that DOX was rapidly released to the cytoplasm as well as to the cell nucleus. MTT studies revealed a markedly enhanced drug efficacy of DOX-loaded Dex-SS-PCL micelles as compared to DOX-loaded reduction-insensitive Dex-PCL micelles. These reduction-responsive biodegradable micelles have appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.

A new class of pH-responsive capsules based on metal-phenolic networks (MPNs) for anticancer drug loading, delivery and release is reported. The fabrication of drug-loaded MPN capsules, which is based on the formation of coordination complexes between natural polyphenols and metal ions over a drug-coated template, represents a rapid strategy to engineer robust and versatile drug delivery carriers.

Currently, biomedical engineering is rapidly expanding, especially in the areas of drug delivery, gene transfer, tissue engineering, and regenerative medicine. A prerequisite for further development is the design and synthesis of novel multifunctional biomaterials that are biocompatible and biologically active, are biodegradable with a controlled degradation rate, and have tunable mechanical properties. In the past decades, different types of α-amino acid-containing degradable polymers have been actively developed with the aim to obtain biomimicking functional biomaterials. The use of α-amino acids as building units for degradable polymers may offer several advantages: (i) imparting chemical functionality, such as hydroxyl, amine, carboxyl, and thiol groups, which not only results in improved hydrophilicity and possible interactions with proteins and genes, but also facilitates further modification with bioactive molecules (e.g., drugs or biological cues); (ii) possibly improving materials biological properties, including cell-materials interactions (e.g., cell adhesion, migration) and degradability; (iii) enhancing thermal and mechanical properties; and (iv) providing metabolizable building units/blocks. In this paper, recent developments in the field of α-amino acid-containing degradable polymers are reviewed. First, synthetic approaches to prepare α-amino acid-containing degradable polymers will be discussed. Subsequently, the biomedical applications of these polymers in areas such as drug delivery, gene delivery and tissue engineering will be reviewed. Finally, the future perspectives of α-amino acid-containing degradable polymers will be evaluated.

A systematic and quantitative study on the role of capsule stiffness in cellular processing was performed using hyaluronic acid capsules with tunable stiffness constructed via continuous assembly of polymers.