Microfluidic Encapsulation of Prickly Zinc‐Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy

Abstract

Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof-of-concept, Prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH-responsive polymer; and the surface has been modified with a novel synthesized ligand, 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication.

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

“…Herein, we employed a microfluidic emulsion selfassembly approach for the generation of inverse opal GO hydrogel scaffolds for cell enrichment and 3D culture. Microfluidic techniques have emerged as advanced methods for fabricating microstructured materials due to their ability in executing precise operations on small quantities of fluids [28][29][30][31][32][33][34]. Thus, scaffolds with tunable pore sizes and morphologies could be generated by polymerizing and replicating the assembled microfluidic emulsions in the GO and N-isopropylacrylamide (NIPAM) dispersed solution.…”

Microfluidics for Production of Particles: Mechanism, Methodology, and Applications

“…Based on this idea, core/shell structures were widely applied into encapsulating pre‐existed NPs to improve their stability, biocompatibility, and targeting ability. For example, Zhang et al encapsulated prickly zinc‐doped copper oxide nanoparticles with a carbonic anhydrase IX targeting ligand modified spermine‐acetalated dextran (Spermine‐AcDEX) . Comparing to the pristine NPs, the newly produced core/shell nanohybrids obtained a better human plasma stability (aggregation time 5 min vs 120 min), a reduced toxicity toward normal fibroblast cells (3T3), but an enhanced targeting ability toward human breast cancer (MCF‐7).…”

Synthesis and Surface Engineering of Inorganic Nanomaterials Based on Microfluidic Technology

“…The degradation of the POD was accelerated by the hydrogen peroxide (H 2 O 2 ) to trigger the release of atorvastatin, which was maintained for more than 24 h. Moreover, the multifunctional oxidized dextran nanocarriers consisting of drug-loaded PSi and gold nanoparticles have been synthesized by using a similar approach, which can be used for controlled drug delivery and X-ray computed tomography (CT) imaging for liver failure theranostics ( Figure 12 c) [ 166 ]. Santos et al have also deposited pH-responsive spermine-modified acetalated dextran (SpAcDx) on the surface of pre-synthesized zinc-doped copper oxide (Zn-CuO) nanoparticles by microfluidic technology for tumor microenvironment-responsive therapy ( Figure 12 d) [ 167 ]. The targeting ligand VD1142 was grafted on a SpAcDx shell to specifically recognize the over-expressed transmembrane protein, carbonic anhydrase IX, in cancer cells.…”

“…( c ) Schematic illustration of synthesis procedure of multifunctional nanoparticles by microfluidics (reproduced from [ 166 ], with permission from the Wiley-VCH Verlag GmbH & Co, 2018). ( d ) Schematic illustration of the microfluidic synthesis of SpAcDx-coated Zn-CuO nanoparticles, and their specific tumor targeting and anti-proliferative effect (reproduced from [ 167 ], with permission from the Wiley-VCH Verlag GmbH & Co, 2017).…”