Large nanoparticles (NPs; >100 nm) can accumulate in the tumor because of the enhanced permeation and retention effect. However, large NPs generally locate next to the blood vessel and are difficult to diffuse within a dense collagen matrix, causing uneven distribution within the tumor. Here, we designed reversibly assembled and disassembled micelles loaded with Fe 3 O 4 and hypocrellin (HC) for ferroptosis and sonodynamic therapy of cancer. Poly(ethylene glycol)−poly(propylene sulfide) (PEG−PPS), an reactive oxygen species (ROS)-responsive amphiphilic polymer, was used to form micelles with Fe 3 O 4 and HC in the core. Upon ultrasound irradiation, ROS was generated by HC for the disassembly of micelles and also for sonodynamic therapy, while realizing a size switch. The released Fe 3 O 4 dissolves to produce Fe 2+ , which catalyzes hydrogen peroxide to form hydroxyl radicals ( • OH). Sonodynamic and ferroptosis therapies generate a synergistic antitumor effect, offering a smart platform for cancer therapy.

Combined chemotherapy and sonodynamic therapy (chemo-SDT) based on the nanoplatform/nanocarrier is a potential antitumor strategy that has shown higher therapeutic efficacy than any monotherapy. Therefore, a safe and effective multifunctional system with a concise design and simple preparation process is urgently needed. In this work, by using a one-step cross-linking method, a multifunctional nanosystem, which employs phycocyanin nanoparticles (PCNPs) as a nanocarrier to deliver the chemotherapy drug docetaxel (DTX) and a nanosonosensitizer to generate reactive oxygen species (ROS), was prepared and evaluated (PCNP-DTX). Under low-intensity ultrasound irradiation, PCNP-DTX retained the ROS generation ability of phycocyanin and caused the destruction of mitochondrial potential. PCNP was also revealed to be an acidic and ultrasound-sensitive carrier with good biocompatibility. In addition to its cumulation behavior in tumors, PCNP can achieve tumor-targeted delivery and release of DTX. PCNP-DTX has also been proven to have a significant chemo-SDT synergy effect when low-intensity ultrasound was applied, showing enhanced antitumor activity both in vitro and in vivo. This study provides a concise yet promising nanoplatform based on the natural protein phycocyanin for achieving an effective, targeted, and synergetic chemo-SDT for antitumor therapy.

Background Chinese natural herbal formula modified Xi-Xin-Tang III (mXXTIII) exhibits therapeutic effects for Alzheimer’s disease(AD). This study aimed to explore the underlying mechanism of mXXTIII for treating AD and discover the main active ingredients and potential drug targets through a combination of network pharmacology-based strategy and molecular docking technique. Methods Single herbs in mXXTIII were screened for active ingredients, and target proteins were predicted. Target screening for AD was performed to establish a disease target database. Subsequently, a protein-protein interaction network was constructed and the correlation between proteins in the network was used to obtain gene clusters, export the subnetwork, and analyze the biological processes facilitated by the targets in this subnetwork. GO and KEGG enrichment analyses of key genes were conducted using the DAVID database. Finally, molecular docking of critical targets and active ingredients was conducted and their interaction patterns were visualized. Results The research received 81 active ingredients, 519 targets, and 3089 disease targets. A total of 264 potential targets of mXXTIII against AD were identified by drawing a Venn diagram and the top action pathways were recognized according to GO and KEGG enrichment analysis. Conclusion Multiple active ingredients, targets, and pathways may be involved in intrinsic molecular actions of mXXTIII in the recovery of AD. The major active ingredients (quercetin, baicalein, formononetin, etc.), critical targets, and key pathways could have played more important roles. The findings may provide a reference for further studies and assessments on the mechanism of resisting AD.