Synthesis of Doxorubicin and miRNA Stimuli-Sensitive Conjugates for Combination Therapy.

Methods Mol Biol

Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.

Published: November 2019

Recent advances in combination therapy by using chemotherapeutic drugs and small noncoding RNAs have highlighted the need for optimization of such agents to allow their carriage in a single delivery system. This protocol details the synthesis of a doxorubicin prodrug, where a NHS coupling reaction was used to sensitize the drug to the proteolytic activity of tumor microenvironments. The design of a lipid-modified miRNA by an S-S coupling reaction is also described. Modification of both, doxorubicin and miRNA, facilitated their simultaneous incorporation into mixed micelles for use in combination therapy against tumor cells.

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9220-1_8DOI Listing

Publication Analysis

Top Keywords

combination therapy
12
synthesis doxorubicin
8
doxorubicin mirna
8
coupling reaction
8
mirna stimuli-sensitive
4
stimuli-sensitive conjugates
4
conjugates combination
4
therapy advances
4
advances combination
4
therapy chemotherapeutic
4

Similar Publications

Background: The presence of multiple comorbid pathologic features in late-onset dementia has been well documented across cohort studies that incorporate autopsy evaluation. It is likely that such mixed pathology potentially confounds the results of interventional trials that are designed to target a solitary pathophysiologic mechanism in Alzheimer's disease and related dementias (ADRD).

Method: The UK ADRC autopsy database was screened for participants who had previously engaged in therapeutic interventional trials for Alzheimer's disease, vascular cognitive impairment, dementia, and/or ADRD prevention trials from 2005 to the present.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Biogen, Cambridge, MA, USA.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of tau aggregates. Research in animal models has generated hypotheses on the underlying mechanisms of the interaction between Aβ and tau pathology. In support of this interaction, results from clinical trials have shown that treatment with anti-Aβ monoclonal antibodies (mAbs) affects tau pathology.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Fundacion Neuropolis, Zaragoza, Zaragoza, Spain.

Background: The therapeutic management of dementia with Lewy bodies (LBD) is a challenge given the high sensitivity to drugs in this disease. This is particularly sensitive with regard to the management of parkinsonism. In particular, treatment of motor symptoms with levodopa or dopaminergic agonists poses a risk of worsening cognitive and behavioral symptoms.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Anti-amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti-amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

L & J Bio, Co., Ltd, Seoul, Songpa-Gu, Korea, Republic of (South).

Background: Neurofibrillary tangles (NFTs), along with amyloid beta plaque, are neuropathological aggregates of Alzheimer's Disease (AD). Hyperphosphorylated tau is responsible for the NFTs formation and further neurodegeneration in AD. The hippocampal region and the entorhinal cortex (EC) have been a major focus of AD research because the deposits of hyperphosphorylated tau protein and NFT in these regions are correlated with memory deficits.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!