In situ apolipoprotein E-enriched corona guides dihydroartemisinin-decorating nanoparticles towards LDLr-mediated tumor-homing chemotherapy

Li, Zhenbao; Zhu, Jiaojiao; Wang, Yongqi; Li, Dan; Zheng, Shunzhe; Liu, Yin; Luo, Cong; Zhang, Huicong; Liu, Zhong; Li, Wei; Wang, Jian; Gui, Shuangying; Cai, Biao; Wang, Yongjun; Sun, Jin

doi:10.1016/j.ajps.2019.05.002

Cited by 25 publications

(17 citation statements)

References 40 publications

(52 reference statements)

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“…S6, 1.62 and 1.33 times). This phenomenon may be attributed to the EPR effect [42,[48][49][50], which was favorable for the suppression of tumor cells. As shown in Fig.…”

Section: Biodistribution Testmentioning

confidence: 99%

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Zong

et al. 2021

Preprint

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Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug-resistance as a carrier to overcome MDR and improve the anti-tumor effect of paclitaxel (PTX). The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells, and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to H22 subcutaneous tumor-bearing mice. This work proves the reduction sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

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“…S6, 1.62 and 1.33 times). This phenomenon may be attributed to the EPR effect [42,[48][49][50], which was favorable for the suppression of tumor cells. As shown in Fig.…”

Section: Biodistribution Testmentioning

confidence: 99%

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Zong

et al. 2021

Preprint

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“…Li and co-workers formulated and evaluated PLGA-based nanoparticles containing dihydroartemisinin by emulsion solvent evaporation technique [ 128 ]. Dihydroartemisinin was conjugated via an ester linker to the terminal carboxyl of PLGA-PEG2000-COOH.…”

Section: Nanoparticlesmentioning

confidence: 99%

“…This evaluation displayed approximately 3.1-fold greater in cancerous 4T4 cells when compared to the non-cancerous 3T3 cells. Pharmacokinetics studies revealed a prolonged circulation time of the nanoparticles which was 6.2 h [ 128 ]. In addition, an in vivo antitumor efficacy study showed a reasonably delayed growth of the tumor when compared to the control groups.…”

Section: Nanoparticlesmentioning

confidence: 99%

Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria

Alven

Aderibigbe

2020

Pharmaceutics

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Cancer, malaria, and leishmaniasis remain the deadly diseases around the world although several strategies of treatment have been developed. However, most of the drugs used to treat the aforementioned diseases suffer from several pharmacological limitations such as poor pharmacokinetics, toxicity, drug resistance, poor bioavailability and water solubility. Artemisinin and its derivatives are antimalarial drugs. However, they also exhibit anticancer and antileishmanial activity. They have been evaluated as potential anticancer and antileishmanial drugs but their use is also limited by their poor water solubility and poor bioavailability. To overcome the aforementioned limitations associated with artemisinin and its derivatives used for the treatment of these diseases, they have been incorporated into nanoparticles. Several researchers incorporated this class of drugs into nanoparticles resulting in enhanced therapeutic outcomes. Their potential efficacy for the treatment of parasitic infections such as malaria and leishmaniasis and chronic diseases such as cancer has been reported. This review article will be focused on the nanoparticles formulations of artemisinin and derivatives for the treatment of cancer, malaria, and leishmaniasis and the biological outcomes (in vitro and in vivo).

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“…Apolipoprotein E (ApoE), an endogenous protein (40–70 μg/mL), is composed of 299 amino acid residues and has a molecular weight of approximately 36 kDa. The structure of ApoE segregates into two ordered segments connected by residues 165–200, which are random segments [ 19 , 20 ]. ApoE has many important functions.…”

Section: Introductionmentioning

confidence: 99%

Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo

Xin

Liu

et al. 2021

J Nanobiotechnol

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Background The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery. Methods PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied. Results The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. Conclusions The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery. Graphical Abstract

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In situ apolipoprotein E-enriched corona guides dihydroartemisinin-decorating nanoparticles towards LDLr-mediated tumor-homing chemotherapy

Cited by 25 publications

References 40 publications

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria

Novel brain-targeted nanomicelles for anti-glioma therapy mediated by the ApoE-enriched protein corona in vivo

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