Photothermal therapy (PTT) combined with chemotherapy, a promising strategy for breast cancer treatment, has a high potential to control drug release, reduce multidrug resistance, and improve therapeutic efficacy. The challenge is how to realize tumor ablation in deeper tissue and NIR‐controlled drug delivery. Herein, tumor acidity and near‐infrared light (NIR) responsive folic acid (FA) functionalized polydopamine (DPA) nanoparticles (NPs) are developed for doxorubicin (DOX) and epigallocatechin‐3‐gallate (EGCG) dual delivery. With the assistance of NIR, the cellular uptake of DOX‐EGCG/DPA‐FA NPs is about three‐ to sixfold higher when compared with the free DOX group and the control group without NIR irradiation. Moreover, biodistribution study in vivo indicates that DPA‐FA NPs can enhance tumoral accumulation, penetration, retention of drugs, and display a ≈4‐ and 19‐fold higher intra‐tumoral distribution than that of the DPA NPs and free drug groups at 24 h postinjection. Furthermore, 60% of breast cancer‐bearing mice survive over 70 days in the DOX‐EGCG/DPA‐FA NPs group. Additionally, DOX‐EGCG/DPA‐FA NPs can effectively boost therapeutic efficacy by inducing significant suppression of tumor growth and angiogenesis, and enhancement of apoptosis and necrosis of breast cancer cells. Taken together, DOX‐EGCG/DPA‐FA NPs may have potential applications as a useful nanoscale vector for enhanced cancer therapy.
Background
Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown.
Methods
In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays.
Results
We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation.
Conclusions
Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.
Malignant tumors are tremendous heath problems facing by the medical world. In order to achieve the purpose of curing malignant tumor, numerous therapeutic strategies have been developed. Radiotherapy is one of the main therapeutic strategies for malignant tumors. Current imaging strategies cannot display exact infiltrating margins, radio-resistance generated by irradiated tissue, and intercurrent damage to healthy tissues during radiotherapy. Therefore, novel strategies to solve these problems are urgently needed. Nanomaterials have specific physical and biological properties that can help clinician to distinguish margins of infiltrating tumors as a novel contrast agent. Besides, nanoparticles can significantly enhance the effect of radiotherapy by generating reactive oxygen species (ROS) or influence cell cycle. In addition, nanomaterials can also help in diminishing the intercurrent damage caused by radiotherapy. So nanomaterials have very promising prospect in the radiotherapy of malignant tumors. This review mainly focuses on the applications of nanomaterials in radiotherapy for malignant tumors; especially it applies to lesion imaging and their radiosensitizing effects.
Nerve guide conduits (NGCs) can replace autogenous nerve grafting in the treatment of peripheral nerve system (PNS) injury. However, the modulus of the polyurethane NGCs that affects the outcome of...
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