Glioma is characterized by high mortality and low postoperative survival. Despite the availability of various therapeutic approaches and molecular typing, the treatment failure rate and the recurrence rate of glioma remain high. Given the limitations of existing therapeutic tools, nanotechnology has emerged as an alternative treatment option. Nanoparticles, such as polydopamine (PDA)-based nanoparticles, are embodied with reliable biodegradability, efficient drug loading rate, relatively low toxicity, considerable biocompatibility, excellent adhesion properties, precisely targeted delivery, and strong photothermal conversion properties. Therefore, they can further enhance the therapeutic effects in patients with glioma. Moreover, polydopamine contains pyrocatechol, amino and carboxyl groups, active double bonds, catechol, and other reactive groups that can react with biofunctional molecules containing amino, aldehyde, or sulfhydryl groups (main including, self-polymerization, non-covalent self-assembly, π-π stacking, electrostatic attraction interaction, chelation, coating and covalent co-assembly), which form a reversible dynamic covalent Schiff base bond that is extremely sensitive to pH values. Meanwhile, PDA has excellent adhesion capability that can be further functionally modified. Consequently, the aim of this review is to summarize the application of PDA-based NPs in glioma and to acquire insight into the therapeutic effect of the drug-loaded PDA-based nanocarriers (PDA NPs). A wealthy understanding and argument of these sides is anticipated to afford a better approach to develop more reasonable and valid PDA-based cancer nano-dru g delivery systems. Finally, we discuss the expectation for the prospective application of PDA in this sphere and some individual viewpoints.

As is known to all, glioma, a global difficult problem, has a high malignant degree, high recurrence rate and poor prognosis. We analyzed and summarized signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β, TCS/mTORC1 signal pathway, JAK/STAT signal pathway, MAPK signaling pathway, the relationship between BBB and signal pathways and the mechanism of key enzymes in glioma. It is concluded that Yap1 inhibitor may become an effective target for the treatment of glioma in the near future through efforts of generation after generation. Inhibiting PI3K/Akt/mTOR, Shh, Wnt/β-Catenin, and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

Purpose:Nanoparticles of the basal polydopamine-loaded temozolomide guided by Pep-1 as a navigator were constructed for the chemotherapy and photothermal of glioblastoma. methods:The active groups such as catechenol aminocarboxyl group and super adhesive of polydopamine were used to perform Schiff base reaction with temozolomide with amino group and Pep-1 with thiol group after functionalization to obtain Pep-1@PDA-TMZA NPs. The size and morphology were characterized by dynamic light scattering and transmission electron microscopy. The loading and assembly of the drug were analyzed by Fourier transform infrared spectroscopy and ultraviolet spectroscopy The biocompatibility of the nanoparticle carrier Pep-1@PDA was verified in U87 cells in vitro, and the cellular uptake and toxicity of Pep-1@PDA-TMZA NPs were investigated.In vivo antitumor activity study investigated the tumor inhibition of Pep-1@PDA-TMZA NPs by temozolomide chemotherapy combined with the photothermal effect of 808nm laser irradiation in tumor environment. Results:DLS characterization revealed that the particle size was approximately 140 nm. The prepared nanoparticles had excellent dispersion stability and good biocompatibility in water and biological buffers. Pep-1@PDA-TMZA NPs had a narrow particle size distribution, homogeneous size, spherical,and smooth surface, which can be easily penetrated and can accumulate at the tumor site via the EPR effect.The Schiff base bond in the nanoparticles was a type of reversible dynamic covalent bond with extreme sensitivity to pH value. That is, its stability was positively correlated with pH value. Hence, lower pH values indicated worse stability. Therefore, under the acidic environment of the tumor, the dynamic covalent Schiff base bond of Pep-1@PDA-TMZA NPs can be broken reversibly, and TMZA is released, thereby exerting a chemotherapeutic effect in antitumor therapy.Under 808-nm laser irradiation,Pep-1@PDA-TMZA NPs can convert light energy into thermal energy after absorbing NIR to achieve the antitumor photothermal effect.Moreover, as the concentration of TMZA increased, the cytotoxicity produced by the tumor cells was significantly enhanced, showing a significant concentration dependence. When the Pep-1@PDA-TMZA NPs concentration was increased to 250 μ g / ml combined with photothermal treatment, the U87 cells and C6 cells were inhibited by 90.81% and 82.29%, respectively.In vivo studies have shown that, compared with other treatment groups, Pep-1@PDA-TMZA NPs + (Laser) had about 77.13% (P <0.05) after conventional blood tests and H & E staining analysis of major organs such as heart, liver, spleen, lung and kidney, indicating that Pep-1@PDA-TMZA NPs does not cause damage to major organs while anti-tumor Conclusion:Pep-1- @PDA-TMZA NPs, modified with polydopamine-loaded by Pep-1, not only has considerable load rate, strong penetration, biocompatibility and targeting, but also has accurate navigation function, most importantly, Pep-1@PDA-TMZA NPs can have the dual therapeutic effects of chemotherapy and photothermal therapy and can target receptor-mediated IL-13Rα2 to promote antitumor effects. Therefore, it can be used as a potential targeted nano-delivery particle in glioblastoma treatment.

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p &lt; 0.05).Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.