PMID- 37043939 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20230509 IS - 1095-7103 (Electronic) IS - 0021-9797 (Linking) VI - 642 DP - 2023 Jul 15 TI - Microfluidic formulation of anticancer peptide loaded ZIF-8 nanoparticles for the treatment of breast cancer. PG - 810-819 LID - S0021-9797(23)00540-4 [pii] LID - 10.1016/j.jcis.2023.03.172 [doi] AB - Anticancer peptides (ACPs) are promising antitumor drugs owning to their great cancer cell targeting and anticancer effects as well as low drug resistance. However, many of the ACPs have non-specific toxicity and can be easily degraded by the enzymes after administration. Therefore, drug delivery systems (DDSs) are required to shield these peptides from degradation and induce targeted delivery. In this paper, a high performance microfluidic device was used to fabricate the zeolitic imidazolate framework (ZIF-8) encapsulating an ACP (At3) recently developed by our group. The microfluidic device allowed for efficient and rapid mixing to generate ACP loaded nanoparticles (NPs) with controllable properties at high production rate (120 mL/min) and high encapsulation efficiency. The ZIF-8 NPs synthesised by microfluidic processing showed lower polydispersity index (PDI) than the conventional method, demonstrating an improved size uniformity. Encapsulating At3 into the ZIF-8 (At3@ZIF-8) significantly reduced the hemolytic effect and provided a pH-controlled release of At3 peptide. At3@ZIF-8 showed higher anticancer effect than the unloaded peptide at the same concentration due to the enhanced cell uptake by the ZIF-8 NPs. The NPs were able to inhibit the growth of the multicellular tumour spheroids (MCTSs) and damage the mitochondrial membrane of the MCF-7 breast cancer cells. In vivo experiments demonstrated that the At3@ZIF-8 NPs inhibited the growth of MCF-7 tumours in nude mice without changing the biochemical properties of the blood or the histopathological properties of vital organs. Therefore, the development of At3 loaded NPs provides an alternative approach in ACP delivery which can broaden the application of ACP-based cancer therapy. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Qiu, Jinguo AU - Qiu J AD - School of Pharmacy, Changzhou University, Changzhou 213164, China. FAU - Tomeh, Mhd Anas AU - Tomeh MA AD - Department of Chemical and Biological Engineering, University of Shenfield, Sheffield S1 3JD, UK. FAU - Jin, Yi AU - Jin Y AD - School of Pharmacy, Changzhou University, Changzhou 213164, China; Department of Pharmacy, Wujin People's Hospital, Changzhou 213000, China. FAU - Zhang, Bo AU - Zhang B AD - School of Pharmacy, Changzhou University, Changzhou 213164, China. FAU - Zhao, Xiubo AU - Zhao X AD - School of Pharmacy, Changzhou University, Changzhou 213164, China; Department of Chemical and Biological Engineering, University of Shenfield, Sheffield S1 3JD, UK. Electronic address: xiubo.zhao@cczu.edu.cn. LA - eng PT - Journal Article DEP - 20230330 PL - United States TA - J Colloid Interface Sci JT - Journal of colloid and interface science JID - 0043125 RN - 1318-02-1 (Zeolites) RN - 0 (Antineoplastic Agents) SB - IM MH - Animals MH - Mice MH - *Zeolites/chemistry MH - Mice, Nude MH - Microfluidics MH - *Antineoplastic Agents/chemistry MH - *Nanoparticles/chemistry MH - Drug Delivery Systems MH - *Neoplasms/drug therapy OTO - NOTNLM OT - Anticancer peptides OT - Cancer OT - Drug delivery OT - Microfluidics OT - Nanoparticles OT - ZIF-8 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/13 06:00 MHDA- 2023/05/09 06:42 CRDT- 2023/04/12 18:05 PHST- 2022/12/04 00:00 [received] PHST- 2023/03/11 00:00 [revised] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/05/09 06:42 [medline] PHST- 2023/04/13 06:00 [pubmed] PHST- 2023/04/12 18:05 [entrez] AID - S0021-9797(23)00540-4 [pii] AID - 10.1016/j.jcis.2023.03.172 [doi] PST - ppublish SO - J Colloid Interface Sci. 2023 Jul 15;642:810-819. doi: 10.1016/j.jcis.2023.03.172. Epub 2023 Mar 30.