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.
Background: Obstructive sleep apnea (OSA) is a multi-component disorder, which has many comorbidities, including cognitive impairment. Although its potential risk factors were unknown, they could affect the patient’s quality of life and long-term prognosis. Objective: The purpose of this study was to investigate the application of urinary Alzheimer’s disease-associated neurofilament protein (AD7c-NTP) levels in the assessment of cognitive impairment in OSA patients, and to analyze the predictive value of potential high-risk factors on cognitive impairment in OSA patients. Methods: 138 young and middle-aged adults were recruited and underwent overnight polysomnographic recording, Montreal Cognitive Assessment (MoCA), and urinary AD7c-NTP test. AD7c-NTP and other factors were further applied as biomarkers to develop a cognition risk prediction model. Results: Compared with the control, OSA patients showed significantly lower MoCA scores and higher urinary AD7c-NTP concentrations, while the severe OSA group appeared more significant. The urinary AD7c-NTP level of the OSA cognitive impairment group was higher than that of the non-cognitive impairment group. The results of regression analysis showed that urinary AD7c-NTP level was an independent predictor of cognitive impairment in OSA patients. Based on urinary AD7c-NTP levels and other selected factors, a multimodal prediction model for assessing the risk of cognitive impairment in OSA patients was initially established. Conclusion: The increased urinary AD7c-NTP level could be used as a relevant peripheral biomarker of cognitive impairment in OSA patients. A model using urinary AD7c-NTP combined with other factors was developed and could accurately assess the cognition risk of OSA patients.
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