Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination

Zhao, Pengfei; Qu, Jingkun; Wu, Aihua; Wang, Shuang; Tang, Xueping; Ou, Ante; Zhang, Jiaxin; Xu, Yi; Zhao, Qiang; Huang, Yongzhuo

doi:10.1016/j.nantod.2022.101448

Cited by 20 publications

(18 citation statements)

References 64 publications

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“…CI < 1, CI = 1, and CI > 1 represent antagonistic effects, additive effects, and synergistic effects, respectively. [ 43,44 ] As exhibited in Figure A,B and Figure S3, Supporting Information, all groups displayed clear combined potency. The optimal synergistic mass ratio of PTX and CTS on 4T1 cells was 1:2, with the lowest CI of 0.606 (Figure 1B).…”

Section: Resultsmentioning

confidence: 85%

A Dual‐Targeting Liposome Enhances Triple‐Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation

Luo

Yang

Yan

et al. 2023

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Immunotherapy gains increasing focus in treating triple‐negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP‐1 and chondroitin sulfate (CS) dual‐modified liposome co‐loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP‐1‐PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript‐3 (STAT3) activation. CS/LyP‐1‐PC Lip enhances cellular uptake through p32 and CD44 dual receptor‐mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2‐type tumor‐associated macrophage, and myeloid‐derived suppressor cell, thus reversing ITM. Markedly, the dual‐targeting liposome shows superior anti‐tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.

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Section: Resultsmentioning

confidence: 85%

A Dual‐Targeting Liposome Enhances Triple‐Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation

Luo

Yang

Yan

et al. 2023

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“…To further clarify the regulatory effect of CpG-EXO/TGM on the tumor microenvironment at the tissue level. On the day after the fifth treatment, the mice were euthanized, GBM tissue was obtained, and the proportion of relevant immune cells in the tumor tissue was detected . According to the flow cytometry results, it could be seen that saline and free drugs have little effect on regulating the tumor microenvironment.…”

Section: Resultsmentioning

confidence: 99%

“…On the day after the fifth treatment, the mice were euthanized, GBM tissue was obtained, and the proportion of relevant immune cells in the tumor tissue was detected. 68 According to the flow cytometry results, it could be seen that saline and free drugs have little effect on regulating the tumor microenvironment. CpG-EXO/TGM could significantly stimulate the maturation of DCs in vivo (Figures S32A, S33, and 7C) and further promote the infiltration of CD3 + + CD8 + T cells in GBM tissues (Figures S32B, S34, and 7F).…”

Section: Stat3 According To Previous Reports Gl Can Down-regulatementioning

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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“…Zhao et al fabricated albumin/lactoferrin hybrid biomimetic nanoparticles (BSA/LFNP) to co-deliver SHK and DSF to target glioma energy metabolism. 129 SHK, PKM2 inhibitor, can inhibit the glycolysis of tumor cells. Disulfiram (DSF) inhibits the ALDH1L1 enzyme in the 10-formyl-tetrahydrofolate-NADH-ATP metabolism axis, which can inhibit the supply of ATP and interfere with tumor energy metabolism.…”

Section: Biomimetic Nanoparticlesmentioning

confidence: 99%

Promising Nanomedicines of Shikonin for Cancer Therapy

Yan¹,

Li²,

Sun³

et al. 2023

IJN

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Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of Lithospermum erythrorhizon, shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.

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Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination

Cited by 20 publications

References 64 publications

A Dual‐Targeting Liposome Enhances Triple‐Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation

A Dual‐Targeting Liposome Enhances Triple‐Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation

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

Promising Nanomedicines of Shikonin for Cancer Therapy

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