A safe, simple and efficient doxorubicin prodrug hybrid micelle for overcoming tumor multidrug resistance and targeting delivery

Bao, Yuling; Yin, Mingxing; Hu, Xiaomeng; Zhuang, Xiangting; Sun, Yu; Guo, Yuanyuan; Tan, Songwei; Zhang, Zhiping

doi:10.1016/j.jconrel.2016.06.003

Cited by 134 publications

(68 citation statements)

References 48 publications

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“…DOX is reported to kill tumor cells by inducing apoptosis and loss of mitochondrial membrane integrity, which is an early event in apoptotic signaling. 35 Subsequently, the damaged mitochondrial membrane causes a decrease in mitochondrial membrane potential (MMP). Therefore, we determined the effect of the LHD/miR-375 on MMP using a JC-1 kit.…”

mentioning

confidence: 99%

Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

Xue¹,

Yu²,

Liu³

et al. 2017

IJN

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Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/miR-375 overcame drug efflux and delivered miR-375 and DOX into MDR HepG2/ADR cells or HCC tissues. MiR-375 delivered by LHD/miR-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of miR-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/miR-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that miR-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of miR-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application.

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mentioning

confidence: 99%

Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

Xue¹,

Yu²,

Liu³

et al. 2017

IJN

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“…The release profiles of AB3 from AB3-loaded micelles were studied in a glass apparatus at 37 °C in a release medium at pH 5.3 or 7.4 39 . Briefly, AB3-loaded unimolecular micelles (5 mg) dispersed in a medium (5 mL) were enclosed in a dialysis bag with a molecular weight cut-off of 2 kDa.…”

Section: Methodsmentioning

confidence: 99%

AB3-loaded and tumor-targeted unimolecular micelles for medullary thyroid cancer treatment

et al. 2017

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Medullary thyroid cancer (MTC) is often resistant to standard therapies, emphasizing the need for the development of other treatments. A new histone deacetylase inhibitor, AB3, can effectively inhibit MTC cell proliferation in vitro. However, its poor aqueous solubility and stability, fast clearance, and lack of tumor targeting ability limit its in vivo application. Therefore, multifunctional unimolecular micelles were developed for targeted delivery of AB3 for MTC therapy. The unimolecular micelles exhibited a spherical core–shell structure, uniform size distribution, and excellent stability. AB3 was encapsulated into the hydrophobic core of the unimolecular micelles, thus significantly enhancing its aqueous solubility and stability. KE108, a somatostatin analog possessing high affinity to all five subtypes of SSTR, was used as an MTC-targeting ligand. In vitro cellular uptake analyses demonstrated that the KE108 exhibited superior targeting ability in MTC cells compared to octreotide, the first clinically used somatostatin analog. Moreover, the AB3-loaded and KE108-conjugated unimolecular micelles exhibited the best efficacy in suppressing MTC cell growth and tumor marker expression in vitro. Furthermore, AB3-loaded, KE108-conjugated micelles demonstrated the best anticancer efficacy in vivo without any apparent systemic toxicity, thereby offering a promising approach for targeted MTC therapy.

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“…Nanoparticle‐based therapeutics have been considered as some of the most promising platforms in drug delivery applications due to their ability to increase drug accumulation in solid tumours by enhanced permeability and retention (EPR) and MDR reversal through bypassing or inhibiting P‐gp activity (Bao et al . ). Furthermore, Basak et al .…”

Section: Nanoparticlesmentioning

confidence: 97%

“…Nanoparticle-based therapeutics have been considered as some of the most promising platforms in drug delivery applications due to their ability to increase drug accumulation in solid tumours by enhanced permeability and retention (EPR) and MDR reversal through bypassing or inhibiting P-gp activity (Bao et al 2016). Furthermore, Basak et al (2014) reported that SL-capped ZnO nanoparticle-mediated C. albicans cell death occurs via membrane bursting followed by oozing out of proteins and intracellular materials.…”

Section: Nanoparticlesmentioning

confidence: 99%

Microbial biosurfactants: current trends and applications in agricultural and biomedical industries

et al. 2019

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Synthetic surfactants are becoming increasingly unpopular in many applications due to previously disregarded effects on biological systems and this has led to a new focus on replacing such products with biosurfactants that are biodegradable and produced from renewal resources. Microbially derived biosurfactants have been investigated in numerous studies in areas including: increasing feed digestibility in an agricultural context, improving seed protection and fertility, plant pathogen control, antimicrobial activity, antibiofilm activity, wound healing and dermatological care, improved oral cavity care, drug delivery systems and anticancer treatments. The development of the potential of biosurfactants has been hindered somewhat by the myriad of approaches taken in their investigations, the focus on pathogens as source species and the costs associated with large‐scale production. Here, we focus on various microbial sources of biosurfactants and the current trends in terms of agricultural and biomedical applications.

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A safe, simple and efficient doxorubicin prodrug hybrid micelle for overcoming tumor multidrug resistance and targeting delivery

Cited by 134 publications

References 48 publications

Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma

AB3-loaded and tumor-targeted unimolecular micelles for medullary thyroid cancer treatment

Microbial biosurfactants: current trends and applications in agricultural and biomedical industries

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