Dehydrocurvularin-loaded mPEG-PLGA nanoparticles for targeted breast cancer drug delivery: preparation, characterization, <i>in vitro</i>, and <i>in vivo</i> evaluation

Dehydrocurvularin (DCV) is a promising lead compound for anti-cancer therapy. Unfortunately, the development of DCV-based drugs has been hampered by its poor solubility and bioavailability. Herein, we prepared a DCV-loaded mPEG-PLGA nanoparticles (DCV-NPs) with improved drug properties and therapeutic efficacy. The spherical and discrete particles of DCV-NPs had a uniform diameter of 101.8 ± 0.45 nm and negative zeta potential of −22.5 ± 1.12 mV (pH = 7.4), and its entrapment efficiency (EE) and drug loading (DL) were ∼53.28 ± 1.12 and 10.23 ± 0.30%, respectively. In vitro the release of DCV-NPs lasted for more than 120 h in a sustained-release pattern, its antiproliferation efficacy towards breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1) was better than that of starting drug DCV, and it could be efficiently and rapidly internalised by breast cancer cells. In vivo DCV-NPs were gradually accumulated in tumour areas of mice and significantly suppressed tumour growth. In summary, loading water-insoluble DCV onto nanoparticles has the potential to be an effective agent for breast cancer therapy with injectable property and tumour targeting capacity.</p

The diagnosis-by-maltreatment interaction effect in the left thalamus.

<p>Left: Statistical parametric map depicting interaction effect in the left thalamus (<i>p</i> < 0.05, FWE corrected). Color scales represent F-values. Right: The interaction graph showing left thalamic gray matter volume differences between the groups, in which adolescent GAD patients with childhood maltreatment have more gray matter volumes in the left thalamus than those without childhood maltreatment and both HCs. GAD, generalized anxiety disorder, HCs, healthy controls, CM, childhood maltreatment, WCM, without childhood maltreatment.</p

Increased right putaminal gray matter volume in adolescent GAD patients compared to healthy controls (<i>p</i> < 0.05, FWE corrected).

<p>Color scales represent t-values.</p

Endogenous connections weighted by Bayesian model average in high suicide risk group (HSR), low suicide risk group (LSR) and healthy controls group (HC).

<p>Group mean estimates and SD (in brackets) are reported for endogenous connections which was weighted by Bayesian model average, the endogenous connections of all groups combined means that were significantly greater than zero across the three groups. We also report the group differences, which were identified using a series of ANOVAs. PCC = posterior cingulate cortex; MPFC = medial prefrontal cortex; “*” means significant statistical difference (statistical threshold <i>p</i><0.05).</p

Demographic, Questionnaire data of adolescent GAD patients and healthy controls.

<p>Means and standard deviations (±) are given.</p><p>GAD, generalized anxiety disorder; HCs, healthy controls; CTQ, childhood trauma questionnaire; BDI, the Beck Depression Inventory; PSWQ, the Penn State Worry Questionnaire; CM, childhood maltreatment; WCM, without childhood maltreatment.</p

Five hypothesized dynamic casual models during 2-back task.

<p>Each model includes the left medial prefrontal cortex (MPFC) and the ipsilateral posterior cingulate cortex (PCC), in which the arrows indicate extrinsic stimulation and functional connections direction. M1, M2 and M3 comprised bi-directional connections with respectively driving input into PCC or MPFC or both of the regions. M4 only contained unidirectional connection from the PCC to MPFC with driving input into PCC and M5 was completely opposite to M4. M1, M4 and M2 were identified as the optimal models in HSR, LSR and HC respectively. HSR: schizophrenic patients with high suicide risk; LSR: schizophrenic patients with low suicide risk; HC: healthy controls.</p

Regions with significant activations at rest state compared with 2-back task (<i>p</i><0.05, FWE corrected).

<p>Regions with significant activations at rest state compared with 2-back task (<i>p</i><0.05, FWE corrected).</p

Statistical parametric map depicting the positive association between childhood maltreatment (Childhood Trauma Questionnaire [CTQ] scores) and left thalamic gray matter volume (mean contrast values) in GAD patients (<i>p</i> < 0.05, FWE corrected).

<p>Color scales represent t-values.</p

Regions with significant activations at rest state among three groups compared with 2-back task.

<p>From A to D (upper part), brain areas are left medial prefrontal cortex (MPFC), left posterior cingulate cortex (PCC), left middle frontal gyrus and right precentral gyrus (<i>p</i><0.005, cluster >20). The signal changes in MPFC and PCC in the three groups are shown below (a and b). Error bars indicated 2 standard errors (SE), *<i>p<</i>0.05.</p

The demographic and clinical characteristics for high suicide risk group (HSR), low suicide risk group (LSR) and healthy controls group (HC).

<p>Data reflect mean (SD) unless otherwise stated. “–” reflect not applicable; “*” means significant statistical difference (statistical threshold <i>p</i><0.05). WAIS-I = Information subscale of the Wechsler Adult Intelligence Scale-Chinese Revised; WAIS-DS = Digit Symbol subscale of the Wechsler Adult Intelligence Scale-Chinese Revised; SAPS = Scale for the Assessment of Positive Symptoms; SANS = Scale for the Assessment of Negative Symptoms; SSRS = Schizophrenia Suicide Risk Scale; CPZ = Chlorpromazine. The proportion correct responses and response time(s) for correct responses were the performance during 2-back task.</p