A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization DOI Creative Commons
Tingting Yang, Yuzhu Hu,

Junming Miao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(6), P. 2658 - 2671

Published: Feb. 16, 2022

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) well-known as one main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart drug efficacy. Herein, therapeutic nanosystem (SPP-ARV-825) constructed by incorporating BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into complex micelle (SPP) composed substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy acid) (mPEG-PDLLA, PP), which could penetrate BBB target tumor. Subsequently, released engenders antitumor effect via attenuating cells proliferation, inducing apoptosis suppressing M2 polarization through inhibition IRF4 promoter transcription phosphorylation STAT6, STAT3 AKT. Taken together, our work demonstrates versatile role efficacy SPP-ARV-825 against glioma, may provide novel strategy therapy future.

Language: Английский

Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy DOI Open Access
Qi Zhan,

Kaikai Yi,

Xiaoteng Cui

et al.

Neuro-Oncology, Journal Year: 2022, Volume and Issue: 24(11), P. 1871 - 1883

Published: March 19, 2022

Abstract Background Targeting glioblastoma (GBM) energy metabolism through multiple metabolic pathways has emerged as an effective therapeutic approach. Dual inhibition of phospholipid and mitochondrial with cytoplasmic phospholipase A2 (cPLA2) knockdown metformin treatment could be a potential strategy. However, the strategic prerequisite is to explore carrier capable co-delivering combination cross blood-brain barrier (BBB) preferentially accumulate at GBM site. Methods Blood exosomes (Exos) were selected delivery carriers. The cellular uptake Exos effects strategy evaluated in primary cells. In vivo GBM-targeted efficiency anti-GBM efficacy tested patient-derived xenograft (PDX) model. Results Here, we showed that Exos-mediated cPLA2 siRNA/metformin combined regulate for personalized treatment. Genomic analysis experiments polymerase 1 transcript release factor (PTRF, biomarker GBM) positively regulated by cells, confirming feasibility Further, co-load siRNA (sicPLA2) co-deliver them across BBB into tissue. was impaired this (Exos-Met/sicPLA2). PDX model, systemic administration Exos-Met/sicPLA2 reduced tumor growth prolonged survival. Conclusions Our findings demonstrated Exos-based sicPLA2 selectively targeted achieve antitumor effects, showing its therapy patients.

Language: Английский

Citations

80
Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma DOI Creative Commons

Dongya Zhang,

Sidan Tian, Yanjie Liu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 11, 2022

Abstract Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to existence blood-brain barrier (BBB) and difficulty maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation achieve BBB crossing tumor penetration drugs. Synthesized crosslinking pullulan poly(deca-4,6-diynedioic acid) (PDDA) loaded with temozolomide indocyanine green (ICG), nanogels are inert endogenous oxidative conditions but selectively disintegrated ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation active targeting. The controlled on lesions excites ICG deforms cumulated trigger burst release for facilitated permeation infiltration into distal cells. These NIR-activatable suppress growth orthotopic stem cells-bearing mouse models significantly extended survival.

Language: Английский

Citations

78
Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives DOI Creative Commons

Qinglong Guo,

Xingliang Dai, Mengyuan Yin

et al.

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: June 9, 2022

Abstract Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it associated with poor prognosis. Its characteristics of being highly invasive undergoing heterogeneous genetic mutation, as well presence blood–brain barrier (BBB), have reduced efficacy GBM treatment. The emergence a novel therapeutic method, namely, sonodynamic therapy (SDT), provides promising strategy for eradicating tumors via activated sonosensitizers coupled low-intensity ultrasound. SDT can provide tumor killing effects deep-seated tumors, such tumors. However, conventional cannot effectively reach region kill additional cells, especially cells. Efforts should be made to develop method help agents pass through BBB accumulate in With development multifunctional nanosensitizers newly emerging combination strategies, ability selectivity greatly improved are accompanied fewer side effects. In this review, we systematically summarize findings previous studies on GBM, focus recent developments directions future research.

Language: Английский

Citations

77
3D bioprinted organ‐on‐chips DOI
Sajjad Rahmani Dabbagh, Misagh Rezapour Sarabi, Mehmet Tugrul Birtek

et al.

Aggregate, Journal Year: 2022, Volume and Issue: 4(1)

Published: May 1, 2022

Abstract Organ‐on‐a‐chip (OOC) platforms recapitulate human in vivo‐like conditions more realistically compared to many animal models and conventional two‐dimensional cell cultures. OOC setups benefit from continuous perfusion of cultures through microfluidic channels, which promotes viability activities. Moreover, chips allow the integration biosensors for real‐time monitoring analysis interactions responses administered drugs. Three‐dimensional (3D) bioprinting enables fabrication multicell with sophisticated 3D structures that closely mimic tissues. 3D‐bioprinted are promising tools understanding functions organs, disruptive influences diseases on organ functionality, screening efficacy as well toxicity drugs organs. Here, common techniques, advantages, limitations each method reviewed. Additionally, recent advances, applications, potentials emulating various organs presented. Last, current challenges future perspectives discussed.

Language: Английский

Citations

73
A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization DOI Creative Commons
Tingting Yang, Yuzhu Hu,

Junming Miao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(6), P. 2658 - 2671

Published: Feb. 16, 2022

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) well-known as one main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart drug efficacy. Herein, therapeutic nanosystem (SPP-ARV-825) constructed by incorporating BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into complex micelle (SPP) composed substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy acid) (mPEG-PDLLA, PP), which could penetrate BBB target tumor. Subsequently, released engenders antitumor effect via attenuating cells proliferation, inducing apoptosis suppressing M2 polarization through inhibition IRF4 promoter transcription phosphorylation STAT6, STAT3 AKT. Taken together, our work demonstrates versatile role efficacy SPP-ARV-825 against glioma, may provide novel strategy therapy future.

Language: Английский

Citations

71