Self-Assembled Nanostructures of Red Fluorescent Amphiphilic Block Copolymers as Both Imaging Probes and Drug Carriers

Abstract

We report a red-fluorescent drug delivery system formed by biodegradable and biocompatible amphiphilic A-B-A block copolymers. Each polymer consists of a red fluorescent dye covalently bonded in the middle of hydrophobic block (B) of polylactone, tethered at both ends with poly[(oligo ethylene glycol) methyl ether methacrylate] (POEGMA) as the hydrophilic block. Two types of polylactones, i.e., semicrystalline poly(ε-caprolactone) (PCL) and amorphous poly(δ-decalactone) (PDL), respectively, were incorporated as the hydrophobic segment in the block copolymers. Using transmission electron microscopy, we characterized the self-assembled nanostructures formed by these amphiphilic block copolymers in mixtures of water/tetrahydrofuran or water/dimethylformamide. All of these polymers remained highly fluorescent in water, although some extent of aggregation-induced fluorescence quenching was still observed. Among the three types of polymers presented here, the polymer (RPO-3) containing an amorphous block of PDL showed the highest drug-loading capacity and the largest extent of drug release in acidic media. RPO-3 micelles loaded with doxorubicin as a model of anticancer drug showed sustainable intracellular release and cytotoxicity against HeLa cells.

Sourcing, thermodynamics, and ring-opening (co)polymerization of substituted δ-lactones: a review

“…26A). 138 ROP of δ-DL using TBD and a red-fluorescent dye diol (DPTBT) as an initiator was first performed. Functionalization of the hydroxyl group with bromoisobutyryl bromide was then performed, prior to ATRP of OEGMA with this macroinitiator.…”

Bioinspired Fluorescent Polymers: Synthesis, Processing, and Applications†

“…For instance, Wang and co‐workers reported synthesis of red‐fluorescent amphiphilic A‐B‐A block copolymers. [ 17 ] Specifically, the hydrophobic block (B) of polylactone was firstly grafted by ring‐opening polymerization (ROP) from a derivative of thiophene‐flanked benzothiadiazole as the initiator, followed by growth of the hydrophilic block of poly[(oligo ethylene glycol) methyl ether methacrylate] (POEGMA) by atom transfer radical polymerization. The resulting amphiphilic block copolymers ( SAP‐2 ) could be dispersible into the water without the addition of surfactants.…”

“…Our recent research has focused on fluorescent and photostable synthetic polymers that resemble the structure and functionality of fluorescent proteins. [ 11‐20 ] Our molecular design and synthesis strategy started by tethering poly(caprolactones) from a series of organic fluorophores bearing bishydroxyl groups via controllable ring‐opening polymerization. The resulting polymers, containing a single fluorophore in the middle of each polymer chain, are highly fluorescent and photostable in solid states when the polymer chain reaches a threshold length to segregate the fluorophores and prevent aggregation‐caused fluorescence quenching.…”

Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles

“…In addition to that, we have also explored the drug delivery capability of δ-decalactone homopolymer (an amorphous polymer) by utilising it as an oil to fabricate nanoemulsion [ 15 ]. Due to the higher hydrophobicity of poly(δ-decalactone) (PDL)-based amphiphilic copolymers, lower critical micelle concentration, higher drug loading and a faster and complete release of hydrophobic guests are expected from them compared to their counterparts of similar molecular weight [ 12 , 13 , 16 ]. Moreover, due to the amorphous nature of PDL, a higher degradation rate in aqueous medium is expected compared to semicrystalline and crystalline poly(esters), which will be beneficial in certain drug delivery applications [ 13 , 17 ].…”