Glycoprotein Ib-regulated micro platelet ghost for biosafe distribution and photothermal oncotherapy

光热治疗 化学 血小板 体外 血小板活化 生物物理学 细胞生物学 纳米技术 免疫学 材料科学 生物 生物化学
作者
Jiahui Zou,Jianhua He,Xiaobo Wang,Yajie Wang,Chenchen Wu,Mengya Shi,Hu‐Lin Jiang,Zimei Wu,Jianping Liu,Wenli Zhang
出处
期刊:Journal of Controlled Release [Elsevier]
卷期号:351: 341-360 被引量:14
标识
DOI:10.1016/j.jconrel.2022.09.036
摘要

Despite the tremendous theranostics potential of nano-scale drug delivery system (NDDS) in oncology field, their tumor-targeting efficiency and safety remain major challenges due to their proneness of off-target accumulation through widespread vascular endothelial gaps (up to 1 μm). To address this problem, in this research, micro-sized cellular platelet "ghosts" (PGs, 1.32 μm, platelet without inner granules and coagulation) were employed as carriers to ship hollow gold nanoparticles (HGNs, 58.7 nm), forming a hierarchical biosafe system (PG@HGNs) to reduce normal tissue interception and enhance tumor targeting delivery of HGNs for improved photothermal therapy. PGs were prepared by an optimized "swelling-extrusion-elution" method, HGNs were loaded in PGs (PG@HGNs) through a "hypotonic dialysis" method and the safety and biodistribution of the system was evaluated in vitro and in vivo. In in vitro condition that stimulated the tumoral vessel acidic microenvironment (pH = 6.5), PG@HGNs were demonstrated with enhanced membrane fluidity through down-regulation of the glycoprotein Ib expressed on the PGs. This change induced a burst release of nano-sized HGNs which were capable to traverse vascular endothelium layer on a tumor-endothelial cell transwell model, whilst the micro-sized PG carriers were intercepted. In comparison to nano-sized platelet membrane-coated carriers (PM@HGNs), PG@HGNs showed enhanced internalization and cytotoxicity to 4T1 cells. In animal models, PG@HGNs remarkably prolonged circulation most likely due to the presence of "self-recognition" receptor-CD47 of PGs, and effectively reduced normal tissue interception via the micro-scale size effect. These both contributed to the significantly improved tumor targeting efficiency of HGNs. PG@HGNs generated the greater antitumor photothermal efficacy alongside safety in the animals compared to PM@HGNs. Collectively, this study demonstrated the potential of the micro-scale PGs equipped with adjusted membrane GP Ib as biosafe vehicles for HGNs or possibly other nanodrugs. THE STATEMENT OF SIGNIFICANCE: Despite the tremendous theranostics potentials, the safety and tumor-targeting efficiency of nano-scale drug delivery systems (NDDS) are compromised by their undesirable accumulation in normal tissues with widespread vascular endothelial gaps, such as many tumor-targeted NDDSs still accumulated much in liver and/or spleen. Herein, we explored a micro-nano biomimetic cascade delivery system to address the above drawbacks. By forming a hierarchical biosafe system, micro-sized platelet "ghost" (PGs, 1.32 μm) was employed as tumor-targeted delivery carrier to transport hollow gold nanoparticles (HGNs, 58.7 nm). It was demonstrated that this micro-size system could maintain platelet membrane structure thus prolong in vivo circulation, while avoiding extravasation into normal tissues. PG@HGNs could sensitively respond to the acidic microenvironment near tumor vessel via down-regulation of glycoprotein Ib and rapidly release "nano-bullets"-HGNs to further penetrate into the tumor tissues through EPR effect, thus enhancing photothermal efficacy generated by HGNs under NIR irradiation. Collectively, the micro-scaled PGs could be biosafe vehicles for improved tumor-targeted delivery of HGNs or possibly other nanodrugs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Patrick完成签到 ,获得积分10
4秒前
overlood完成签到 ,获得积分10
4秒前
没头脑和不高兴完成签到 ,获得积分10
12秒前
Byby完成签到 ,获得积分10
15秒前
qausyh完成签到,获得积分10
20秒前
xzn1123应助wodetaiyangLLL采纳,获得10
23秒前
lixinyue完成签到 ,获得积分10
33秒前
JamesPei应助研友_LN32Mn采纳,获得10
36秒前
快乐的幼丝完成签到 ,获得积分10
39秒前
我独舞完成签到 ,获得积分10
41秒前
蟲先生完成签到 ,获得积分10
41秒前
46秒前
复杂觅山完成签到 ,获得积分10
46秒前
胜胜糖完成签到 ,获得积分10
47秒前
幸运草完成签到 ,获得积分10
50秒前
stiger完成签到,获得积分10
53秒前
昵称吧完成签到 ,获得积分10
54秒前
lilylwy完成签到 ,获得积分10
57秒前
58秒前
胖胖完成签到 ,获得积分10
1分钟前
然后发布了新的文献求助10
1分钟前
回首不再是少年完成签到,获得积分0
1分钟前
科研通AI2S应助刘隅采纳,获得10
1分钟前
CYL完成签到 ,获得积分10
1分钟前
Reader01完成签到 ,获得积分10
1分钟前
kk完成签到 ,获得积分10
1分钟前
香蕉觅云应助然后采纳,获得10
1分钟前
马香芦完成签到,获得积分10
1分钟前
美满的皮卡丘完成签到 ,获得积分10
1分钟前
科研张完成签到 ,获得积分10
1分钟前
小马完成签到 ,获得积分10
1分钟前
鬼见愁应助科研通管家采纳,获得10
1分钟前
在水一方应助科研通管家采纳,获得10
1分钟前
1分钟前
科研通AI2S应助刘隅采纳,获得10
1分钟前
研友_LN32Mn发布了新的文献求助10
1分钟前
缺粥完成签到 ,获得积分10
1分钟前
莫冰雪完成签到 ,获得积分10
1分钟前
EVEN完成签到 ,获得积分10
1分钟前
zwzxtx完成签到 ,获得积分10
2分钟前
高分求助中
좌파는 어떻게 좌파가 됐나:한국 급진노동운동의 형성과 궤적 2500
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Cognitive linguistics critical concepts in linguistics 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
氟盐冷却高温堆非能动余热排出性能及安全分析研究 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3052652
求助须知:如何正确求助?哪些是违规求助? 2709874
关于积分的说明 7418267
捐赠科研通 2354446
什么是DOI,文献DOI怎么找? 1246020
科研通“疑难数据库(出版商)”最低求助积分说明 605951
版权声明 595921