Targeted liposomes for combined delivery of artesunate and temozolomide to resistant glioblastoma

Yang, Wen; Li, Yanfei; Chai, Tianran; Zhang, Dongya; Du, Qiuli; Muhammad, Pir; Hanif, Sumaira; Zheng, Meng; Shi, Bingyang

doi:10.1016/j.biomaterials.2022.121608

Cited by 61 publications

(19 citation statements)

References 57 publications

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“…Currently, receptor-mediated targeted nanodrug delivery systems often rely on modifying exogenous ligands, such as transferrin aptamers, apolipoprotein E peptides, and iRGD peptides. ,− Notably, these targeted nanodrug delivery systems may combine with endogenous proteins to form protein coronas in vivo , resulting in poor targeting . Therefore, we chose serum EXO with TfR as the coating of NPs, which can fully use endogenous Tf to achieve the capacity to target BBB and glioma cells.…”

Section: Resultsmentioning

confidence: 99%

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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Effective drug delivery and prevention of postoperative recurrence are significant challenges for current glioblastoma (GBM) treatment. Poor drug delivery is mainly due to the presence of the blood–brain barrier (BBB), and postoperative recurrence is primarily due to the resistance of GBM cells to chemotherapeutic drugs and the presence of an immunosuppressive microenvironment. Herein, a biomimetic nanodrug delivery platform based on endogenous exosomes that could efficiently target the brain without targeting modifications and co-deliver pure drug nanomicelles and immune adjuvants for safe and efficient chemo-immunotherapy against GBM is prepared. Inspired by the self-assembly technology of small molecules, tanshinone IIA (TanIIA) and glycyrrhizic acid (GL), which are the inhibitors of signal transducers and activators of transcription 3 from traditional Chinese medicine (TCM), self-assembled to form TanIIA-GL nanomicelles (TGM). Endogenous serum exosomes are selected to coat the pure drug nanomicelles, and the CpG oligonucleotides, agonists of Toll-like receptor 9, are anchored on the exosome membrane to obtain immune exosomes loaded with TCM self-assembled nanomicelles (CpG-EXO/TGM). Our results demonstrate that CpG-EXO/TGM can bind free transferrin in blood, prolong blood circulation, and maintain intact structures when traversing the BBB and targeting GBM cells. In the GBM microenvironment, the strong anti-GBM effect of CpG-EXO/TGM is mainly attributed to two factors: (i) highly efficient uptake by GBM cells and sufficient intracellular release of drugs to induce apoptosis and (ii) stimulation of dendritic cell maturation and induction of tumor-associated macrophages polarization by CpG oligonucleotides to generate anti-GBM immune responses. Further research found that CpG-EXO/TGM can not only produce better efficacy in combination with temozolomide but also prevent a postoperative recurrence.

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Section: Resultsmentioning

confidence: 99%

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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“…Quantitative siCFL1 fluorescence analysis showed similar permeability of SeMSN(siCFL1)@P(MNs)Ang2 and SeMSN(siCFL1)@LipoAng2, with higher cumulative transport than naked free siCFL1 (10-fold) and SeMSN(siCFL1)@P(MNs) (5-fold). The angiopep-2 peptides on the outer surface played a dominant role in BBB traversal via low-density lipoprotein receptor-related protein 1 (LRP-1), , which is overexpressed on the BBB and rrU87MG cells (Figure S12). Similar to the BBB penetration results, angiopep-2-enhanced rrU87MG targeting was observed at 4 h (Figure S13), and endocytosis behavior was further detected by CLSM (Figure B).…”

Section: Resultsmentioning

confidence: 99%

Radiation-Triggered Selenium-Engineered Mesoporous Silica Nanocapsules for RNAi Therapy in Radiotherapy-Resistant Glioblastoma

et al. 2023

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Radiotherapy-resistant glioblastoma (rrGBM) remains a significant clinical challenge because of high infiltrative growth characterized by activation of antiapoptotic signal transduction. Herein, we describe an efficiently biodegradable selenium-engineered mesoporous silica nanocapsule, initiated by high-energy X-ray irradiation and employed for at-site RNA interference (RNAi) to inhibit rrGBM invasion and achieve maximum therapeutic benefit. Our radiation-triggered RNAi nanocapsule showed high physiological stability, good blood-brain barrier transcytosis, and potent rrGBM accumulation. An intratumoral RNAi nanocapsule permitted low-dose X-ray radiation-triggered dissociation for cofilin-1 knockdown, inhibiting rrGBM infiltration. More importantly, tumor suppression was further amplified by electron-affinity aminoimidazole products converted from metronidazole polymers under X-ray radiation-exacerbated hypoxia, which sensitized cell apoptosis to ionizing radiation by fixing reactive oxygen species-induced DNA lesions. In vivo experiments confirmed that our RNAi nanocapsule reduced tumor growth and invasion, prolonging survival in an orthotopic rrGBM model. Generally, we present a promising radiosensitizer that would effectively improve rrGBM-patient outcomes with low-dose X-ray irradiation.

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“…Hao et al revealed that experimental results showed that the latter cationic micelles have higher anti-tumor effects compared to single drug delivery [ 52 , 145 ]. Bhattarai et al used a solvent evaporation method to create pH-responsive poly(2-(dimethylamino) ethyl methacrylate)-block-poly(2-(diisopropylamino) ethyl methacrylate) micelles [ 136 ]. The latter micelles were used to reverse MDR in lung cancer by co-delivering chemotherapeutic agents and siRNA [ 146 ].…”

Section: Combination Treatment Strategiesmentioning

confidence: 99%

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy

2022

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Cancer therapies have advanced tremendously throughout the last decade, yet multiple factors still hinder the success of the different cancer therapeutics. The traditional therapeutic approach has been proven insufficient and lacking in the suppression of tumor growth. The simultaneous delivery of multiple small-molecule chemotherapeutic drugs and genes improves the effectiveness of each treatment, thus optimizing efficacy and improving synergistic effects. Nanomedicines integrating inorganic, lipid, and polymeric-based nanoparticles have been designed to regulate the spatiotemporal release of the encapsulated drugs. Multidrug-loaded nanocarriers are a potential strategy to fight cancer and the incorporation of co-delivery systems as a feasible treatment method has projected synergistic benefits and limited undesirable effects. Moreover, the development of co-delivery systems for maximum therapeutic impact necessitates better knowledge of the appropriate therapeutic agent ratio as well as the inherent heterogeneity of the cancer cells. Co-delivery systems can simplify clinical processes and increase patient quality of life, even though such systems are more difficult to prepare than single drug delivery systems. This review highlights the progress attained in the development and design of nano carrier-based co-delivery systems and discusses the limitations, challenges, and future perspectives in the design and fabrication of co-delivery systems.

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Targeted liposomes for combined delivery of artesunate and temozolomide to resistant glioblastoma

Cited by 61 publications

References 57 publications

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Radiation-Triggered Selenium-Engineered Mesoporous Silica Nanocapsules for RNAi Therapy in Radiotherapy-Resistant Glioblastoma

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy

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