Hyaluronic Acid-Shelled Disulfide-Cross-Linked Nanopolymersomes for Ultrahigh-Efficiency Reactive Encapsulation and CD44-Targeted Delivery of Mertansine Toxin

It was and remains a big challenge for cancer nanomedicines to achieve high and stable drug loading with fast drug release in the target cells. Here, we report on novel hyaluronic acid-shelled disulfide-cross-linked biodegradable polymersomes (HA-XPS) self-assembled from hyaluronic acid-<i>b</i>-poly­(trimethylene carbonate-<i>co</i>-dithiolane trimethylene carbonate) diblock copolymer for ultrahigh-efficiency reactive encapsulation and CD44-targeted delivery of mertansine (DM1) toxin, a highly potent warhead for clinically used antibody-drug conjugates. Remarkably, HA-XPS showed quantitative encapsulation of DM1 even with a high drug loading content of 16.7 wt %. DM1-loaded HA-XPS (HA-XPS-DM1) presented a small size of ∼80 nm, low drug leakage under physiological conditions, and fast glutathione-triggered drug release. MTT assays revealed that HA-XPS was noncytotoxic while HA-XPS-DM1 was highly potent to MDA-MB-231 cells with an IC₅₀ comparable to that of free DM1. The in vitro and in vivo inhibition experiments indicated that HA-XPS could actively target MDA-MB-231 cells. Notably, HA-XPS-DM1 while causing little adverse effect could effectively inhibit tumor growth and significantly prolong survival time in MDA-MB-231 human breast tumor-bearing mice. HA-XPS-DM1 provides a novel and unique treatment for CD44-positive cancers

MRI scan of the hip on T1W1 reveals elevated signal intensity on the right gluteus maximus muscle.

<p>Massive irregular, homogeneous, mass-like abnormal signal intensity with unclear boundary was observed in the gluteus maximus muscle, measuring about 151 cm×90 cm, and subcutaneous edema-like signal intensities were observed in the right hip.</p

Left and right upper lungs displayed diffuse, ground-glass shadows with increased intensity.

<p>Left and right upper lungs displayed diffuse, ground-glass shadows with increased intensity.</p

A fresh lesion on the right side of the neck.

<p>The ulcer was oval, with the largest diameter of about 5</p

Information on clinical features and treatments in 30 patients.

+<p>: positive;</p>-<p>: negative;</p><p>*: severe case,</p>K<p>: knee TB,</p>D<p>: type 2 diabetes,</p>S<p>: symptoms commonly associated with tuberculosis, including low-grade fever, night sweats, anorexia and marasmus.</p><p>Good efficacy of drug treatment in nine suspected patients named group I; moderate efficacy of drug treatment in four confirmed and ten suspected patients named group II; poor efficacy of drug treatment in three confirmed and four suspected patients named group III.</p

Hyperplasia of the knee joint synovium, grey and dark in color, with a soft texture, complicated by necrotic tissues.

<p>Some knee joint synovium underwent caseous changes, and articular cartilage necrosis and desquamation were observed. Subchondral bone was exposed, and vermiform bone destruction was observed on the condyle of femur and the margin of the tibial plateau.</p

Enhanced MRI scan shows tuberculous, ring-shaped, signal-intensified lesions in bilateral frontal and parietal lobes, centrum semiovale, peri-lateral ventricular region, basal ganglia regions, thalamus, brainstem and cerebellum.

<p>Enhanced MRI scan shows tuberculous, ring-shaped, signal-intensified lesions in bilateral frontal and parietal lobes, centrum semiovale, peri-lateral ventricular region, basal ganglia regions, thalamus, brainstem and cerebellum.</p

Additional file 1: Table S1. of T2 relaxation time for intervertebral disc degeneration in patients with upper back pain: initial results on the clinical use of 3.0 Tesla MRI

Classification of intervertebral disc degeneration as reported by Pfirrmann et al. [6]. The table descripted the details of classification of intervertebral disc degeneration by Pfirrmann grades. (DOCX 16 kb