泡腾大麻二酚固体分散体掺杂溶解微针通过“TRPV1-NFATc1-ATF3”途径和肿瘤微环境工程促进黑色素瘤治疗。

IF 11.3 1区 医学 Q1 Medicine Biomaterials Research Pub Date : 2023-05-18 DOI:10.1186/s40824-023-00390-x
Jiachen Shi, Qiuling Ma, Wenting Su, Congyan Liu, Huangqin Zhang, Yuping Liu, Xiaoqi Li, Xi Jiang, Chang Ge, Fei Kong, Yan Chen, Ding Qu
{"title":"泡腾大麻二酚固体分散体掺杂溶解微针通过“TRPV1-NFATc1-ATF3”途径和肿瘤微环境工程促进黑色素瘤治疗。","authors":"Jiachen Shi,&nbsp;Qiuling Ma,&nbsp;Wenting Su,&nbsp;Congyan Liu,&nbsp;Huangqin Zhang,&nbsp;Yuping Liu,&nbsp;Xiaoqi Li,&nbsp;Xi Jiang,&nbsp;Chang Ge,&nbsp;Fei Kong,&nbsp;Yan Chen,&nbsp;Ding Qu","doi":"10.1186/s40824-023-00390-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration.</p><p><strong>Methods: </strong>In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO<sub>3</sub> & NaHCO<sub>3</sub>) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the \"one-step micro-molding\" method for boosted transdermal and tumoral delivery of cannabidiol (CBD).</p><p><strong>Results: </strong>Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO<sub>2</sub> bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca<sup>2+</sup> influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca<sup>2+</sup> can not only amplify the effervescent effect but also provide sufficient Ca<sup>2+</sup> with CBD to potentiate the anti-melanoma efficacy. Such a \"one stone, two birds\" strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo.</p><p><strong>Conclusions: </strong>This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"48"},"PeriodicalIF":11.3000,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193696/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the \\\"TRPV1-NFATc1-ATF3\\\" pathway and tumor microenvironment engineering.\",\"authors\":\"Jiachen Shi,&nbsp;Qiuling Ma,&nbsp;Wenting Su,&nbsp;Congyan Liu,&nbsp;Huangqin Zhang,&nbsp;Yuping Liu,&nbsp;Xiaoqi Li,&nbsp;Xi Jiang,&nbsp;Chang Ge,&nbsp;Fei Kong,&nbsp;Yan Chen,&nbsp;Ding Qu\",\"doi\":\"10.1186/s40824-023-00390-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration.</p><p><strong>Methods: </strong>In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO<sub>3</sub> & NaHCO<sub>3</sub>) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the \\\"one-step micro-molding\\\" method for boosted transdermal and tumoral delivery of cannabidiol (CBD).</p><p><strong>Results: </strong>Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO<sub>2</sub> bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca<sup>2+</sup> influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca<sup>2+</sup> can not only amplify the effervescent effect but also provide sufficient Ca<sup>2+</sup> with CBD to potentiate the anti-melanoma efficacy. Such a \\\"one stone, two birds\\\" strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo.</p><p><strong>Conclusions: </strong>This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.</p>\",\"PeriodicalId\":9079,\"journal\":{\"name\":\"Biomaterials Research\",\"volume\":\"27 1\",\"pages\":\"48\"},\"PeriodicalIF\":11.3000,\"publicationDate\":\"2023-05-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193696/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomaterials Research\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1186/s40824-023-00390-x\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials Research","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s40824-023-00390-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

背景:传统的溶解微针(DMNs)在抗黑色素瘤治疗中面临重大挑战,因为缺乏主动推力来实现有效的经皮给药和肿瘤内穿透。方法:本研究采用“一步微成型”的方法,将泡腾组分(CaCO3和NaHCO3)与基于CBD的固体分散体(CBD- sd)相结合,制备出泡腾大麻二酚固体分散体掺杂溶解微针(Ef/CBD-SD@DMNs),促进大麻二酚(CBD)的透皮和肿瘤给药。结果:Ef/CBD-SD@DMNs压入皮肤后,通过质子消除快速产生CO2气泡,显著增强CBD的皮肤渗透性和肿瘤渗透性。Ef/CBD-SD@DMNs到达肿瘤后,可激活瞬时受体电位香兰素1 (TRPV1),增加Ca2+内流,抑制下游NFATc1-ATF3信号,诱导细胞凋亡。此外,Ef/CBD-SD@DMNs升高肿瘤内pH环境触发肿瘤微环境(TME)的工程化,包括肿瘤相关巨噬细胞(tam)的M1极化和T细胞浸润的增加。Ca2+的引入不仅可以放大泡腾效应,还可以为CBD提供足够的Ca2+,从而增强抗黑色素瘤的功效。这种“一石二鸟”的策略结合了透皮给药泡腾效应和TME调节的优势,为CBD在体外和体内获得更强的黑色素瘤生长抑制创造了有利的治疗条件。结论:本研究在经皮给药CBD治疗黑色素瘤方面具有良好的潜力,为皮肤肿瘤的经皮治疗提供了一种简便的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the "TRPV1-NFATc1-ATF3" pathway and tumor microenvironment engineering.

Background: Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration.

Methods: In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the "one-step micro-molding" method for boosted transdermal and tumoral delivery of cannabidiol (CBD).

Results: Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a "one stone, two birds" strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo.

Conclusions: This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biomaterials Research
Biomaterials Research Medicine-Medicine (miscellaneous)
CiteScore
10.20
自引率
3.50%
发文量
63
审稿时长
30 days
期刊介绍: Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
期刊最新文献
Injectable biomimetic hydrogel constructs for cell-based menopausal hormone therapy with reduced breast cancer potential Targeted H2S-mediated gas therapy with pH-sensitive release property for myocardial ischemia-reperfusion injury by platelet membrane Ultrasound Controllable Release of Proteolysis Targeting Chimeras for Triple Negative Breast Cancer Treatment Multifunctional hydrogels based on γ-polyglutamic acid/polyethyleneimine for hemostasis and wound healing Combining gut microbiota modulation and enzymatic-triggered colonic delivery by prebiotic nanoparticles improves mouse colitis therapy
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1