Macromolecule-antitumour drug conjugates can reach tumour sites specifically via the enhanced permeability and retention (EPR) effect. It is desirable to release the drug efficiently from the conjugate at acidic pH in the tumour tissue or in the endosomes of cancer cells. In this study, we attempted to produce a carrier system with a labile chemical bond at acidic pH. Adipic acid dihydrazide (ADH)-chondroitin sulfate (CS) (termed CS-ACH) was synthesised by a two-step method, with the introduction of formyl groups followed by reductive amination using ADH. Doxorubicin (DOX) was conjugated to CS-ACH by simple mixing at acidic pH. The conjugate, designated CS-ACH-DOX, showed gradual drug release pH dependently at 37 °C; after incubation for seven days, more than 60% of DOX was released at pH 4, whereas less than 20% was released at pH 7. CS-ACH-DOX showed in vitro cytotoxicity against Lewis lung carcinoma (LLC) cells, which was less effective than that of DOX itself. However, CS-ACH-DOX inhibited tumour growth more than DOX in LLC tumour-bearing mice. These results suggested that CS-ACH-DOX might accumulate in tumours via the EPR effect and release DOX effectively at acidic pH. CS-ACH-DOX was considered to act as a drug delivery system with tumour targeting.
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http://dx.doi.org/10.1080/1061186X.2017.1327593 | DOI Listing |
Alzheimers Dement
December 2024
AviadoBio, London, London, United Kingdom.
Background: Frontotemporal dementia (FTD) presents with a change in personality, behaviour and language and is the second most common cause of young-onset dementia after Alzheimer's disease. Loss of function mutations in GRN, encoding progranulin (PGRN), causes FTD in the heterozygous state, accounting for 5-10% of all FTD cases. PGRN is essential for normal lysosomal function and neuronal survival.
View Article and Find Full Text PDFCurr Protoc
January 2025
Center for Stem Cell Research and Development (PEDI-STEM), Hacettepe University, Ankara, Turkey.
Bone marrow adipose tissue (BMAT) has garnered significant attention due to its critical roles in leukemia pathogenesis, cancer metastasis, and bone marrow failure. BMAT is a metabolically active, distinct tissue that differs from other fat depots. Marrow adipocytes, closely interacting with hematopoietic stem/progenitor cells and osteoblasts, play a pivotal role in regulating their functions.
View Article and Find Full Text PDFNat Commun
January 2025
Grid Therapeutics, Durham, NC, USA.
GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.
View Article and Find Full Text PDFNat Commun
January 2025
The MOE Key Laboratory of Biosystems Homeostasis & Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Roles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored in hepatocellular carcinoma (HCC). Here we show that LSGs are generally downregulated in HCC tumor tissues compared to non-HCC liver tissues, and low-LSG HCCs show poor prognosis and the activated c-Myc pathway. Among the c-Myc- and patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic HCC formation.
View Article and Find Full Text PDFBrain Inj
January 2025
Direct Biologics, LLC, Austin, Texas, USA.
Objective: Extracellular vesicles (EVs) derived from regenerative mesenchymal stem cells might safely treat traumatic brain injury (TBI). We evaluated the safety and efficacy of a human bone marrow derived mesenchymal stem cell EVs (hBM-MSC EV) investigational product (IP) in a patient with severe TBI.
Design: A single case study employing an IP with a strong safety profile in over 200 patients.
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