Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy

Xu, Hengwu; Li, Chaoqun; Wei, Yinghui; Zheng, Hua; Wang, Binhui; Piao, Ji-Gang; Li, Fanzhu

doi:10.1016/j.bbrc.2021.02.138

Cited by 23 publications

(14 citation statements)

References 22 publications

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“…Upon incubation in an acidic environment, LP@MnAs x exhibited an obvious pH-dependent drug release behavior, whereby cumulative release amounts of 33.47 ± 3.43% and 63.15 ± 1.90% of As were attained at pH of 6.8 and 5.5, respectively ( Figure 2F-G ). The biodegradation of arsenic–manganese complex could be triggered by the acidic environment of the tumor tissue, 17 which could be attributed to the dissociation of the AMO triggered by decreased pH, and the coordination between manganese and arsenic would be weakened in the meantime.…”

Section: Resultsmentioning

confidence: 99%

“…16 Moreover, Mn 2+ can form insoluble complexes with multiple anionic groups, and their subsequent biodegradation can be triggered by the acidic environment of the tumor tissue. 17 The released Mn 2+ can then serve as a T1weighted magnetic resonance imaging (MRI) contrast agent for real-time detection of the release and in vivo distribution of AsO 2 − . 18 Also, Mn 2+ can catalyze the tumor-abundant hydrogen peroxide (H 2 O 2 ) to generate toxic hydroxyl radicals (•OH) via Fenton-like reactions (chemodynamic therapy, CDT) to kill the cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

Jin¹,

Yang²,

Yang³

et al. 2021

IJN

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Purpose A liposome-coated arsenic–manganese complex, denoted as LP@MnAs x was constructed for the targeted delivery of arsenic trioxide (ATO) against carcinoma. Methods Arsenite, the prodrug of ATO, was encapsulated within a liposome via electrostatic interaction with the manganese ions. The as-prepared material was characterized with dynamic light scattering and transmission electron microscopy. The entrapment efficiency and drug loading of arsenic in the carrier were measured using inductively coupled plasma spectrometry. The in vitro release of arsenic was evaluated by using the dialysis bag method. Furthermore, the Fenton-like activity and in vitro cytodynamics research of LP@MnAs x were monitored in this work. And the cellular uptake study was used to investigate the in vitro entry mechanism. Furthermore, the cytotoxicity, cell apoptosis and cell cycle study were performed to evaluate the tumor-killing efficiency. Also, the pharmacokinetic and antitumor studies were investigated in HepG2 tumor-bearing nude mice. Results The as-prepared LP@MnAs x possessed a spherical morphology, uniformly distributed hydrodynamic diameter, and excellent drug-loading efficiency. LP@MnAs x displayed robust stability and sustained-release profile under physiological environments. LP@MnAs x could degrade with high sensitivity to the pH variation in the tumor microenvironment. As such, this could lead to a burst release profile of Mn 2+ and arsenite to achieve a synergistic therapy of chemodynamic therapy and chemotherapy. When compared to the carrier-free arsenate, in vitro experiments revealed that LP@MnAs x exhibited enhanced cellular uptake and tumor-killing efficiency. LP@MnAs x also demonstrated significantly enhanced tumor-specific in vivo distribution of arsenic, prolonged systemic circulation lifetime, and increased accumulation at the tumor site. Conclusion Based on the experimental results, LP@MnAs x is an ideal arsenic-based nanodelivery system, whereby it can improve the non-specific distribution of NaAsO 2 in vivo. Thus, this work can expand the research and application of arsenic trioxide against solid tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

Jin¹,

Yang²,

Yang³

et al. 2021

IJN

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“…These findings align with previously published articles. 42,77 Additionally, Figure 10B shows the in vivo brain accumulation of NP, Ang2-NP, and a third group of nanoparticle samples, i.e., the commercial stabilizer Pluronic F127-stabilized cubosomes. Pluronic F127, a commercially available amphiphilic block copolymer commonly employed in the formulation of cubosomes, was used as a control in this study.…”

Section: Behavior Of Cubosomes In Amentioning

confidence: 99%

Angiopep-2-Functionalized Lipid Cubosomes for Blood–Brain Barrier Crossing and Glioblastoma Treatment

Cai,

Refaat,

Gan

et al. 2024

ACS Appl. Mater. Interfaces

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Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood–brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.

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“…Xuan and colleagues [32] demonstrated that the encapsulation of dibenzazepine in PEGylated Angiopep-2-modified liposomes enhanced its cytotoxicity against glioblastoma stem cells. More recently, PEGylated Angiopep-2-modified liposomes were shown to promote the anti-glioma effect of arsenic trioxide [33].…”

Section: Angiopep-2-decorated Nanoparticlesmentioning

confidence: 99%

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

Habib

Singh

2022

Polymers

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Nanotechnology has opened up a world of possibilities for the treatment of brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver a variety of therapeutic agents, including drugs and nucleic acids. Nanoparticles may also be formulated to contain photosensitizers or, on their own, serve as photothermal conversion agents for phototherapy. Furthermore, nano-delivery agents can enhance the efficacy of contrast agents for improved brain imaging and diagnostics. However, effective nano-delivery to the brain is seriously hampered by the formidable blood–brain barrier (BBB). Advances in understanding natural transport routes across the BBB have led to receptor-mediated transcytosis being exploited as a possible means of nanoparticle uptake. In this regard, the oligopeptide Angiopep-2, which has high BBB transcytosis capacity, has been utilized as a targeting ligand. Various organic and inorganic nanostructures have been functionalized with Angiopep-2 to direct therapeutic and diagnostic agents to the brain. Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders.

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Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy

Cited by 23 publications

References 22 publications

Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

Angiopep-2-Functionalized Lipid Cubosomes for Blood–Brain Barrier Crossing and Glioblastoma Treatment

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

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