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, Qiuling Ma, Wenting Su, Congyan Liu, Huangqin Zhang, Yuping Liu, Xiaoqi Li, Xi Jiang, Chang Ge, Fei Kong, Yan Chen, 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":null,"pages":null},"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, Qiuling Ma, Wenting Su, Congyan Liu, Huangqin Zhang, Yuping Liu, Xiaoqi Li, Xi Jiang, Chang Ge, Fei Kong, Yan Chen, 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\":null,\"pages\":null},\"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}
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.
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.