Eur J Med Chem
August 2025
The advent of targeted protein degradation (TPD) strategies presents unparalleled opportunities for innovating and expediting the development of new drugs. As the most mature TPD technology to date, proteolysis targeting chimeras (PROTACs) reliant on the ubiquitin proteasome system (UPS) have successfully transitioned from the laboratory to phase III clinical trials after nearly two decades of development. In recent years, the gradually emerging degraders engaging lysosomal pathways have further broadened the range of degradation mechanisms and substantially increased the diversity of potential targets and indications, ushering in a new era for the TPD field.
View Article and Find Full Text PDFBackground: The potential nephrotoxicity of cyclosporine A (CsA) has been a problem for treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relationship between CsA blood concentration and acute kidney injury (AKI) in pediatric patients after allo-HSCT remains unclear.
Methods: We performed a retrospective study including pediatric patients who received allo-HSCT in West China Second Hospital of Sichuan University from 2000 to 2022 and collected their clinical data.
Objective: Whether cyclosporine A (CsA) is a risk factor of kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been determined. We aim to comprehensively review the correlation and influencing factors between CsA and kidney injury in patients following allo-HSCT.
Methods: We searched PubMed, Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, VIP, Wanfang and CBM Database from inception to March 2022.
Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. The management of aggressive TNBC remains a formidable challenge. Tumor microenvironment (TME), with the unique features, which can serve as the "soil" for the growth and survival of tumor cells (the "seeds"), plays an important regulatory role in the occurrence, proliferation and metastasis of tumors.
View Article and Find Full Text PDFBioorg Med Chem
September 2022
Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood-brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells.
View Article and Find Full Text PDFGlioblastoma, a common malignancy of the central nervous system, is the most destructive type of brain cancer. Clinical treatment remains a major challenge due to high infiltrative growth and the presence of the blood brain barrier (BBB). Therefore, advanced nanoplatforms that can efficiently cross the BBB and target brain tumours are highly desired.
View Article and Find Full Text PDFThe satisfactory efficient tumor treatment and complete tumor ablation using a mono-therapeutic approach are limited owing to the tumor complexity, diversity, heterogeneity and the multiple pathways involved in tumor pathogenesis. Herein, novel, intelligent and tumor microenvironment (TME)-responsive biotin/R8 peptide co-modified nanocarriers (BRNC) loading paclitaxel (PTX)/glucose oxidase (GOx) were constructed. GOx could catalyze the oxidation of intracellular glucose to gluconic acid and poisonous H2O2 to cause the deterioration of the tumor survival microenvironment, simultaneously achieving starvation and oxidation therapy.
View Article and Find Full Text PDFGlioma is one of the most common primary intracranial tumor, but the current treatments of glioma are far from satisfying. As the major treatment option for malignant glioma, chemotherapy has its own disadvantages, including low chemotherapeutic agents delivery across blood-brain barrier (BBB) and lack of specificity. Therefore, new approach permitting glioma targeting ability that can allow an efficient therapeutic delivery into the glioma regions is urgently required.
View Article and Find Full Text PDFAlthough active targeting liposomes with cancer-specific ligands can bind and internalize into cancer cells, only a few high-efficiency liposomes have been developed so far because traditional single branched ligand modified liposomes generally failed to deliver adequate therapeutic payload. In this paper, we broke the traditional design concept and synthesized the double branched biotin modified cholesterol (Bio-Chol) for the first time. On this basis, different biotin density modified liposomes ((Bio-Chol)Lip, (Bio-Chol)Lip and (Bio-Chol)Lip) were successfully prepared and used as active targeting drug delivery systems for the treatment of breast cancer.
View Article and Find Full Text PDFArch Pharm (Weinheim)
May 2018
A new dual-targeting naproxen prodrug conjugated with glucose and ascorbic acid for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver naproxen to the brain. Naproxen could be released from the prepared prodrugs when incubated with various buffers, mouse plasma, and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vivo over naproxen.
View Article and Find Full Text PDFDrug Deliv
November 2018
Ibuprofen is one of the most potent non-steroid anti-inflammatory drugs (NSAIDs) and plays an important role in the treatment of neurodegenerative diseases. However, its poor brain penetration and serious side effects at therapeutic doses, has hindered its further application. Thus, it is of great interest to develop a carrier-mediated transporter (CMT) system that is capable of more efficiently delivering ibuprofen into the brain at smaller doses to treat neurodegenerative diseases.
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