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In silico and in vitro design of cordycepin encapsulation in liposomes for colon cancer treatment
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Document Title
In silico and in vitro design of cordycepin encapsulation in liposomes for colon cancer treatment
Author
Khuntawee W, Amornloetwattana R, Vongsangnak W, Namdee K, Yata T, Karttunen M, Wongekkabut J
Name from Authors Collection
Affiliations
Kasetsart University; Kasetsart University; Kasetsart University; National Science & Technology Development Agency - Thailand; National Nanotechnology Center (NANOTEC); Chulalongkorn University; Chulalongkorn University; Western University (University of Western Ontario); Western University (University of Western Ontario); Western University (University of Western Ontario)
Type
Article
Source Title
RSC ADVANCES
Year
2021
Volume
11
Issue
15
Page
8475-8484
Open Access
gold, Green Published
Publisher
ROYAL SOC CHEMISTRY
DOI
10.1039/d1ra00038a
Format
Abstract
Cordycepin or 3 '-deoxyadenosine is an interesting anti-cancer drug candidate that is found in abundance in the fungus Cordyceps militaris. It inhibits cellular growth of many cancers including lung carcinoma, melanoma, bladder cancer, and colon cancer by inducing apoptosis, anti-proliferation, anti-metastasis and by arresting the cell cycle. Cordycepin has, however, poor stability and low solubility in water, resulting in loss of its bioactivity. Liposomes can be used to overcome these obstacles. Our aim is to improve cordycepin's anti-colon cancer activity by liposome encapsulation. Cordycepin-encapsulated liposomes were designed and fabricated based on a combination of theoretical and experimental studies. Molecular dynamics (MD) simulations and free energy calculations suggest that phosphatidylcholine (PC) lipid environment is favorable for cordycepin adsorption. Cordycepin passively permeates into PC lipid bilayers without membrane damage and strongly binds to the lipids' polar groups by flipping its deoxyribose sugar toward the bilayer center. Our fabricated liposomes containing 10 : 1 molar ratio of egg yolk PC : cholesterol showed encapsulation efficiency (%EE) of 99% using microfluidic hydrodynamic focusing (MHF) methods. In our in vitro study using the HT-29 colon cancer cell line, cordycepin was able to inhibit growth by induction of apoptosis. Cell viability was significantly decreased below 50% at 125 mu g mL(-1) dosage after 48 h treatment with non-encapsulated and encapsulated cordycepin. Importantly, encapsulation provided (1) a 2-fold improvement in the inhibition of cancer cell growth at 125 mu g mL(-1) dosage and (2) 4-fold increase in release time. These in silico and in vitro studies indicate that cordycepin-encapsulated liposomes could be a potent drug candidate for colon cancer therapy.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
National Research Council of Thailand; Thailand Research Fund (TRF) Research Scholar [RSA6180021]; Kasetsart University; Natural Sciences and Engineering Research Council of Canada (NSERC) the Canada Research Chairs Program
License
CC BY
Rights
Authors
Publication Source
WOS