This paper, written by researchers from Academia University and others, discusses Microfluidic Encapsulation of Prickly Zinc-Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy. The paper is published in an important journal < Advanced Healthcare Meterials>. IF：5.609.

In recent years, the research work of microwave chemical instrument used in the synthesis of materials has become a hot direction of scientific research, which has been paid great attention to by many scholars!

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.

In summary, we synthesized Prickly Zn–CuO NPs via a facile and environment-friendly fabrication protocol. The Prickly NPs exhibited very efficient anticancer effect, even against DOX resistance breast cancer cells. The microfluidic nanoprecipitation enabled the successful encapsulation of the Prickly NPs and shielded them from unspecific damaging of the receptor negative cells. Moreover, we explored the cancer targeting capability of a novel ligand VD1142 and we successfully witnessed the targeting selectivity of Prickly@SpAcDX–PEG–VD1142 toward CA IX overexpressed hypoxia MCF-7 breast cancer cells. Specifically, the intracellular distribution of the NPs indicated that the Prickly@SpAcDX–PEG–VD1142 induced endosomal escape and, more importantly, they disintegrated into small pieces with extra deleterious effect toward disruption of ER and mitochondrial structures in cells through nanopiercing. By evaluating the protein markers for cell apoptosis and comparing the structurally related cell death, we further confirmed that the anticancer mechanism was mainly due to physical damage of the cells instead of Cu2+ induced toxicity. Overall, we engineered Prickly@SpAcDX–PEG–VD1142 for efficient and targeted cancer therapy, which is a very promising and novel nanotherapy that could replace the anticancer drugs. Overall, we envisage that the design of this nanocomposite will open new horizons and bring insights for developing novel and highefficiency anticancer nanomaterials.

Preparation of the Prickly Zn–CuO nanoparticles: Prickly NPs were prepared through a home-made high intensity ultrasonic device (XH-300UL, Beijing Xianghu Science and Technology development Co., Ltd.) as described previously.[31] Typically, 0.15 g of copper acetate monohydrate and 0.055 g of zinc acetate dehydrate were dissolved in 10 mL of double distilled water by stirring, after which 90 mL of ethanol was added to sustain an ethanol/water solution with a volume ratio of 9:1. After 5 min of sonication, 0.8 mL of ammonium hydroxide (28%– 30%) was injected into the reaction cell to adjust the pH to ≈8, and the sonochemical deposition process continued for 1 h (750 W, 100% efficiency). The resultant zinc–copper oxide (Zn–CuO) NPs were then centrifuged and washed twice with double-distilled water and once with ethanol, and then dried under vacuum. The needle Zn–CuO was fabricated according to the above procedure, but using an ethanol/water solution with the volume ratio of 1:9.