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Gliomasdevastating intracranial tumors with a dismal outcomeare in dire need of innovative treatment. Although nanodrugs have been utilized as a target therapy for certain types of solid tumors, their therapeutic effects in gliomas are limited due to the complications of the systemic circulation, blood–brain barrier (BBB), and specific glioma environment. Thus, we aimed to establish a nanoliposome adaptable to different environments by codelivery of shCD163 and doxorubicin (DOX) to treat gliomas. In this study, we first synthesized pH-sensitive DSPE-cRGD-Hz-PEG2000 to form an environmentally self-adaptative nanoliposome (cRGD-DDD Lip) via a thin film method. We used in vitro BBB models, in vitro cell uptake experiments, and in vivo biodistribution assays to confirm the long circulation time and low cell uptake of the cRGD-DDD Lip as a result of the poly(ethylene glycol) (PEG) shell of cRGD-DDD Lip in the neutral pH systemic circulation. Moreover, the cRGD-DDD Lip bypassed the BBB and attached to the intracranial glioma following the removal of the PEG shell and the exposure of cRGD to the weakly acidic tumor microenvironment. We further assembled the shCD163/DOX@cRGD-DDD Lip through cRGD-DDD Lip loading of shCD163 and DOX. In vitro, cell proliferation and self-renewal of glioma cells were inhibited by the shCD163/DOX@cRGD-DDD Lip due to the toxicity of DOX and the suppression of shCD163 via the CD163 pathway. In vivo, the shCD163/DOX@cRGD-DDD Lip disturbed the progression of in situ gliomas by inhibiting the growth and stemness of glioma cells and prevented the recurrence of gliomas after resection. In conclusion, the cRGD-DDD Lip may be a promising nanodrug-loading platform to cope with different environments and the shCD163/DOX@cRGD-DDD Lip may potentially be a novel nanodrug for glioma therapy.
Gliomasdevastating intracranial tumors with a dismal outcomeare in dire need of innovative treatment. Although nanodrugs have been utilized as a target therapy for certain types of solid tumors, their therapeutic effects in gliomas are limited due to the complications of the systemic circulation, blood–brain barrier (BBB), and specific glioma environment. Thus, we aimed to establish a nanoliposome adaptable to different environments by codelivery of shCD163 and doxorubicin (DOX) to treat gliomas. In this study, we first synthesized pH-sensitive DSPE-cRGD-Hz-PEG2000 to form an environmentally self-adaptative nanoliposome (cRGD-DDD Lip) via a thin film method. We used in vitro BBB models, in vitro cell uptake experiments, and in vivo biodistribution assays to confirm the long circulation time and low cell uptake of the cRGD-DDD Lip as a result of the poly(ethylene glycol) (PEG) shell of cRGD-DDD Lip in the neutral pH systemic circulation. Moreover, the cRGD-DDD Lip bypassed the BBB and attached to the intracranial glioma following the removal of the PEG shell and the exposure of cRGD to the weakly acidic tumor microenvironment. We further assembled the shCD163/DOX@cRGD-DDD Lip through cRGD-DDD Lip loading of shCD163 and DOX. In vitro, cell proliferation and self-renewal of glioma cells were inhibited by the shCD163/DOX@cRGD-DDD Lip due to the toxicity of DOX and the suppression of shCD163 via the CD163 pathway. In vivo, the shCD163/DOX@cRGD-DDD Lip disturbed the progression of in situ gliomas by inhibiting the growth and stemness of glioma cells and prevented the recurrence of gliomas after resection. In conclusion, the cRGD-DDD Lip may be a promising nanodrug-loading platform to cope with different environments and the shCD163/DOX@cRGD-DDD Lip may potentially be a novel nanodrug for glioma therapy.
ObjectiveAnxiety and depression are common mental disorders in glioma patients. This study aimed to evaluate the risk factors, prognostic role, and longitudinal changes in anxiety and depression in postoperative glioma patients.MethodsAnxiety and depression were assessed by Hospital Anxiety and Depression Scale at baseline, month (M) 6, M12, M24 and M36 in 270 glioma patients after surgical resection. Furthermore, comprehensive clinic characteristics and treatment-related information were collected.ResultsGender (female vs. male) (P = 0.014, odds ratio (OR) = 1.974), marital status (single/divorced/widowed vs. married) (P = 0.019, OR = 2.172), Karnofsky performance status (KPS) score (≤70 vs. > 70) (P = 0.002, OR = 2.556), World Health Organization (WHO) classification (high-grade glioma (HGG) vs. low-grade glioma (LGG)) (P = 0.005, OR = 2.155), and postoperative complications (yes vs. not) (P = 0.001, OR = 2.525) were independently related to anxiety occurrence. Marital status (single/divorced/widowed vs. married) (P = 0.034, OR = 2.026), KPS score (≤70 vs. > 70) (P < 0.001, OR = 3.880), WHO classification (HGG vs. LGG) (P = 0.032, OR = 1.810), and postoperative complications (yes vs. not) (P = 0.001, OR = 2.602) were independently related to depression occurrence. Besides, anxiety (P = 0.038) and depression (P = 0.013) were linked with shorter overall survival (OS), and depression was an independent risk factor for worse OS (P = 0.040, hazard ratio = 1.596). More importantly, anxiety and depression remained at a high prevalence during a 3-year follow-up.ConclusionGender, marital status, KPS score, WHO classification, and postoperative complications are risk factors for anxiety and depression; moreover, anxiety and depression are at high prevalence continuously and correlated with worse survival in postoperative glioma patients.
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