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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 31 ·6837-6844 · IF 5.344

Active targeting nano-scale bubbles enhanced ultrasound cavitation chemotherapy in Y1 receptor-overexpressed breast cancer

Xuechen Qian,Yinjie Wang,Youfeng Xu,Ling Ma,Nianyu Xue,Zhenqi Jiang,Yi Cao,Ozioma Udochukwu Akakuru,Juan Li,Shengmin Zhang,Aiguo Wu

Ultrasound cavitation therapy has attracted much attention in recent years because the cavitation of microbubbles can be leveraged to boost the infiltration of chemotherapeutic drugs into cancer tissues. For breast cancer therapy, most of the previously reported microbubbles lack specific targeting capacity and permeability. In this study, we have successfully fabricated Y1 receptor ligand (NPY)-modified bubbles, and examined their therapeutic efficacies as size-dependent functions with or without NPY targeting. To achieve this, four types of micro-scale bubbles (MBs or MBs-NPY) and nano-scale bubbles (NBs or NBs-NPY) were comprehensively evaluated. In vivo results indicated that the NBs-NPY group with doxorubicin (DOX) under ultrasound irradiation showed a high tumor suppression effect and a prolonged survival time. Furthermore, the NBs-NPY with DOX group exhibited minimal damage to mouse vital organs, which points to the considerable tolerance of the proposed nanosystem for efficacious breast cancer therapy. In summary, these findings suggest that the developed NPY-targeted NBs could have a broad application prospect in ultrasound cavitation chemotherapy of Y1 receptor-overexpressed breast cancer.

CAS / MDL: 9002-89-5 1338-43-8
研究领域: 肿瘤学 · 治疗学 · 纳米技术 · 超声工程
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Neuropeptide Y Y1 Receptors Meditate Targeted Delivery of Anticancer Drug with Encapsulated Nanoparticles to Breast Cancer Cells with High Selectivity and Its Potential for Breast Cancer Therapy

Juan Li,Zheyu Shen,Xuehua Ma,Wenzhi Ren,Lingchao Xiang,An Gong,Tian Xia,Junming Guo,Aiguo Wu

By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

CAS / MDL: 75-05-8 76-05-1
研究领域: 癌症研究 · 纳米技术 · 药学科学 · 分子生物学
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BIOMATERIALS · 2016 · IF 8.387

Neuropeptide Y Y1 receptor-mediated biodegradable photoluminescent nanobubbles as ultrasound contrast agents for targeted breast cancer imaging

Juan Li,Yuchen Tian,Dingying Shan,An Gong,Leyong Zeng,Wenzhi Ren,Lingchao Xiang,Ethan Gerhard,Jinshun Zhao,Jian Yang,Aiguo Wu

Targeted molecular imaging has attracted great attention in cancer diagnosis and treatment. However, most clinically used ultrasound contrast agents (UCAs) are non-targeted microbubbles seldom used for cancer imaging. Here, we fabricated fluorescent nanobubbles (NBs) by encapsulation of liquid tetradecafluorohexane (C 6 F 14 ) within biodegradable photoluminescent polymers (BPLPs) through an emulsion-evaporation process and conjugation of PNBL-NPY ligand for specific targeting of Y 1 receptors overexpressed in breast tumors. The developed PNBL-NPY modified NBs were uniform in size with good dispersibility and photostability, presenting good ultrasound enhancement. Further, in vitro and in vivo results indicated that the fabricated NBs exhibit high affinity and specificity to Y 1 receptor-overexpressing breast cancer cells and tumors with minimal toxicity and damage to organs. Our developed PNBL-NPY-modified NBs are novel targeted UCAs for safe, efficient and specific targeted breast cancer imaging, and may provide a new nanoplatform for early cancer diagnosis and treatment in the future.

研究领域: 医学影像 · 癌症诊断 · 纳米技术 · 生物医学工程
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BIOMATERIALS · 2018 · IF 8.806

pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time

Zhenqi Jiang,Yuchen Tian,Dingying Shan,Yinjie Wang,Ethan Gerhard,Jianbi Xia,Rong Huang,Yan He,Aiguo Li,Jianchao Tang,Huimin Ruan,Yong Li,Juan Li,Jian Yang,Aiguo Wu

Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y 1 receptor (Y 1 R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging ; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo . Herein, for the first time, we imparted antiphagocytosis capability to Y 1 R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y 1 R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.

研究领域: 癌症治疗 · 纳米医学 · 药理学 · 分子影像 · 生物医学工程
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