Gadolinium/DOTA functionalized poly(ethylene glycol)-block-poly(acrylamide-co-acrylonitrile) micelles with synergistically enhanced cellular uptake for cancer theranostics

Abstract

The combination of diagnostic and therapeutic functions into a nano-carrier could achieve a delivery system with both accurate diagnosis and delivery capabilities. Herein, functionalized polymer of 1,4,7,10-tetraazacyclododecane-1,4,7,10tetraacetic acid-poly(ethyleneglycol)-block-poly(acrylamide-co-acrylonitrile) (DOTA-PEG-b-poly(AAm-co-AN)) was designed and synthesized. Doxorubicin (DOX) and gadolinium ion (Gd 3+ ) was loaded in the hydrophobic core and chelated on the shell of the micelles during the self-assembling process to endow the prepared micelles with drug delivery and magnetic resonance imaging functionalities. Such theranostics micelles exhibited conspicuous accelerated DOX release with elevated temperature and high proton relaxivity r1 (25.88 mM −1 s −1 ). Moreover, the Gd 3+ /DOX loaded micelle presented synergistically enhanced cellular uptake efficiency (2.12 times of that of free DOX) as compared with free drug or that loaded in micelles without Gd 3+ . The micelles provided promising application for chemotherapy and simultaneous enhanced magnetic resonance imaging (MRI) of cancer.

Dendrimer- and copolymer-based nanoparticles for magnetic resonance cancer theranostics

“…Gd-based and manganese-based 176 contrast agents are commonly used T 1 contrast agents for MRI, and they produce efficient positive contrast enhancement in T 1 -weighted imaging. For example, Tong et al 177 designed and synthesized a core-shell nano-carrier using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-poly(ethyleneglycol)-block-poly(acrylamide-co-acrylonitrile) (DOTA-PEG-b-poly(AAm-co-AN)). Gd 3+ ions and DOX were loaded into the hydrophobic core and chelated on the shell during the self-assembly process.…”

Thermoresponsive properties of poly(acrylamide-co-acrylonitrile)-based diblock copolymers synthesized (by PISA) in water

“…3 Indeed, the latter was largely used to engineer thermoresponsive/stimuli-responsive block copolymer systems for drug delivery purposes, cancer theranostics/chemotherapy and photoacoustic imaging. [40][41][42][43][44][45][46][47][48][49][50][51][52] It is generally obtained by radical copolymerization of acrylamide and acrylonitrile in organic solvents, mainly in dimethylsulfoxide (DMSO). Both free radical polymerization (FRP) and reversible deactivation radical polymerization (RDRP) [53][54][55][56][57][58] mechanisms -in particular the reversible addition fragmentation chain transfer (RAFT) -have been used.…”

Thermoresponsive polymer nanocarriers for biomedical applications

“…They also showed that the UCST increased when increasing the copolymer concentration: 6 °C at 1 wt.% to 26 °C at 15.3 wt.% (with a fixed AN content). The P(AAm-co-AN) copolymer has been used as the thermoresponsive block in multiblock copolymers to design thermoresponsive micelles and other nanocarriers [116][117][118][119][120]. Some groups have investigated the influence of the nature of the hydrophobic comonomer on the UCST of acrylamide-based copolymers.…”