Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery

Abstract

Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.

pH/Reduction Dual-Stimuli-Responsive Cross-Linked Micelles Based on Multi-Functional Amphiphilic Star Copolymer: Synthesis and Controlled Anti-Cancer Drug Release

“…In a more acidic condition (pH 5.0) shown in Figure 5B, there was a fast DOX release in the initial time and it then reached a plateau as time went on. The DOX cumulative release percentage improved to 48.6% in the initial 3 h and then reached 81.1% within 110 h. Under this acidic condition, the higher cumulative release was due to the electrostatic interaction between the DOX and micelles decreasing [37]. Moreover, the dissolubility of DOX in mildly acidic solution was relative higher than that in neutral media and the deionization of carboxylic acid groups in MAA units resulted in the shrinkage of the micelles' structure to squeeze the entrapped DOX released from polymer micelles [38].…”

Synthesis and characterization of new functionalized polymer-Fe3O4 nanocomposite particles

“…The magnetic properties of the synthesized nanoparticles can be applied in magnetic resonance imaging (MRI) [17]. Moreover, they can be used as DDS for antibiotics [59], anticancer drugs [60], neurotransmitters [61]. Furthermore, the presence of modifiable functional groups facilitates the attachment of different therapeutic agents.…”

One-step dry synthesis of an iron based nano-biocomposite for controlled release of drugs

“…24,27 The high saturation magnetization (M s ) is observed at 11.2 emu g À1 (corresponding to 0.217 emu for 20 mg mass of the sample) which indicates the presence of magnetite (Fe 3 O 4 ). 15,24,28…”

“…There are several controlled release studies reported for DOX in the literature 1,2,4,7,11,14,17 using GO, 4,20 carbon dots, CNT and supermagnetic nanoparticles such as Fe 3 O 4 . 4,[13][14][15]21 The release of DOX from GO, CNT and carbon dots are preferred due to its higher drug loading capacity (77-90%), and the larger surface area available in the layered materials. 17,18 Xue et al studied the subcellular delivery of doxorubicin from pH-responsive alginate nanogel.…”