ABSTRACT
This paper reports a drug nanovehicle self-assembled from an amine-functionalized block copolymer poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione)-block-poly(1,3-dioxepan-2-one) (PADMC-b-PTeMC), which is prepared by controlable ring-opening block copolymerization attractively in a "one-shot feeding" pathway. The copolymers display high cell-biocompatibility with no apparent cytotoxicities detected in 293T and HeLa cells. Due to their amphiphilic nature, PADMC-b-PTeMC copolymers can self-assemble into nanosized micelles capable of loading anticancer drugs such as camptothecin (CPT) and doxorubicin (DOX). In particular, the outer PADMC shell endows the PADMC-b-PTeMC nanomicelles with pH-dependent control over the micellar morphology, cell uptake efficiency, and the drug release pattern. Confocal inspection reveals the remarkably enhanced cellular internalization of drug loaded micelles by cancerous HeLa cells at relatively lower pH 5.8 simulating the mildly acid microenvironment in tumors. Along with the acidity-triggered volume expansion of micelles, an accelerated CPT release in vitro occurs. The obtained results adumbrate the possibility of completely biodegradable PADMC-b-PTeMC as pH-sensitive drug carriers for tumor chemotherapy.
Subject(s)
Dihydropyridines/administration & dosage , Drug Liberation , Neoplasms/drug therapy , Polymers/administration & dosage , Amines/administration & dosage , Amines/chemistry , Camptothecin/administration & dosage , Camptothecin/chemistry , Dihydropyridines/chemistry , Doxorubicin/administration & dosage , Doxorubicin/chemistry , HeLa Cells , Humans , Hydrogen-Ion Concentration , Polymers/chemistryABSTRACT
This paper reports a novel amphoteric aliphatic polycarbonate bearing both amine and carboxyl groups. In the absence of protection-deprotection chemistry, the multi-functionalized copolymer is synthesized by one-step enzymatic copolymerization. The influences of the reaction conditions including monomer feed ratio and polymerization time are explored. The simultaneous incorporation of amine and carboxyl functionalities provides the copolymer with a pH-tunable self-aggregation feature, leading to various aggregation states including precipitated agglomerate, well-dispersed positively or negatively charged nanoparticles in a controlled manner. The copolymer displays minimal cytotoxicity to 293T and HeLa cells.
Subject(s)
Biocompatible Materials , Biosynthetic Pathways/physiology , Carbonates/chemistry , Polymers/chemistry , Amines/chemistry , Buffers , Carbon Dioxide/chemistry , Drug Delivery Systems/methods , HEK293 Cells , HeLa Cells , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
A facile strategy to perform the boron coordination reaction on a template of nanofibers is developed. Peptides with phenylboronic acid tails (peptidyl boronic acids) are designed and prepared as building blocks that can self-assemble into nanofibers. After the addition of vicinal diol structural motifs to the self-assembling system, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry indicates that the boron coordination reaction occurs on the template of nanofibers, which results in the increase of the width and roughness of the nanofibers as demonstrated by transmission electron microscopy and atomic force microscopy measurements. Because the surface-bound vicinal diol structural motifs have an ability to form hydrogen bonds with the peptide segments on the nanofibers, which restrain and disturb the hydrogen-bonding interaction among the nanofibers, the network structure formed based on the entanglement of nanofibers via hydrogen-bonding interaction is destroyed, which leads to a gel-sol transition. The novel concept of post-self-assembly modification demonstrated here could lead to a new technique for using self-assembled nanostructures in the emerging fields of nanoscience and nanotechnology.
Subject(s)
Boron/chemistry , Nanofibers/chemistry , Nanotechnology/methods , Hydrogen Bonding , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectroscopy, Fourier Transform InfraredABSTRACT
Novel thermo-sensitive magnetomicelles that consist of a magnetic core, Fe(3)O(4)-oleic acid (Fe(3)O(4)-OA), and an amphiphilic surface layer of thermo-sensitive poly(oleic acid-co-N-isopropylacrylamide) P(OA-co-NIPAAm) co-polymer were prepared. Fe(3)O(4) magnetic cores functionalized with double bonds of oleic acid were prepared by suspension-oxidation reaction. Subsequently, by the co-polymerization of hydrophilic NIPAAm, hydrophobic OA and the Fe(3)O(4)-OA magnetic core, the thermo-sensitive amphiphilic polymers (P(OA-co-NIPAAm)) were grafted to obtain Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles. The surface polymeric layer of Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles would self-assemble in aqueous media to form a micellar structure attributed to the amphiphilic P(OA-co-NIPAAm) polymers. The model drug, prednisone acetate, was loaded in the magnetomicelles and in vitro release behavior of loaded drug in magnetomicelles was further investigated, which showed a thermo-sensitive release behavior due to the thermo-sensitive structural changes of the micellar surface layer.