Targeted Delivery of Cordycepin to Liver Cancer Cells Using Transferrin-conjugated Liposomes

Bi, Ye; Zhou, Yanmin; Wang, Mengqiao; Li, Lianlian; Lee, Robert J.; Xie, Jing; Teng, Lesheng

doi:10.21873/anticanres.11944

Cited by 14 publications

(20 citation statements)

References 13 publications

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“…Significant accumulation of BF was detected in the liver, with concentrations of 187 ± 31.0 ng/g in the BF/PEG-LP group and 163 ± 35.0 ng/g in the BF group ( P < 0.01). A similar phenomenon, which is mainly caused by a dramatic increase in BF in the blood before metabolism and excretion, was observed in previous studies [20, 21].…”

Section: Resultssupporting

confidence: 85%

Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution

et al. 2019

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Bufalin, derived from Venenum Bufonis , exerts antitumor effects but has low bioavailability and adverse effects when administered as a single agent. The purpose of this study was to evaluate the physical and chemical properties, antitumor efficacy, general pharmacology, acute toxicity, and tissue distribution profile of bufalin-loaded PEGylated liposomes (BF/PEG-LP), which were prepared in a previous study. To evaluate the safety of the preparation, a red blood cell hemolysis test was performed, which indicated that the hemolysis rate of BF/PEG-LP was significantly lower than that of bufalin alone. Cell viability assay revealed that the blank liposomes were nontoxic. In an in vitro experiment, BF/PEG-LP dose-dependently induced the apoptosis of HepG2, HCT116, A549, and U251 cancer cells, with half-maximal inhibitory concentration (IC 50 ) values of 21.40 ± 2.39, 21.00 ± 3.34, 43.39 ± 6.43, and 31.14 ± 2.58 ng/mL, respectively, at 24 h. Tumor xenograft experiments in nude mice showed that BF/PEG-LP significantly inhibited the growth of U251 cells. Pharmacological evaluation revealed that BF/PEG-LP impacted the general behavior, independent activities, and coordination of mice after a week of administration compared with those of mice in the control group. In an acute toxicity test, the median lethal concentration (LD 50 ) of BF and BF/PEG-LP in mice was 0.156 and 3.03 mg/kg, respectively. Tissue distribution profiles showed that the BF concentration in brain tissue was 20% higher, whereas that in heart tissue was 30% lower when BF/PEG-LP was administered to mice compared with BF. Thus, BF/PEG-LP exhibited lower hemolysis and cytotoxicity and improved pharmacokinetic and antitumor properties compared with bufalin alone, indicating its potential for future pharmacological application, particularly for glioma treatment. Electronic supplementary material The online version of this article (10.1186/s11671-019-3057-0) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 85%

Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution

et al. 2019

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“…The bioactivity of COR quickly decreases under gastric acid conditions. Hence, COR carriers, including gelatin type A nanoparticles [134] and transferrin-conjugated liposomes [143] have been developed to approach this problem.Decreasein toxicity. Several potential strategies are available to decrease the toxicity of COR: (i) low dose of treatment; (ii) natural and designed derivates; (iii) COR carriers for region-targeted treatment and the specific accumulation of COR.…”

Section: Pros and Cons Of Cor In Clinical Applicationsmentioning

confidence: 99%

“…In strategy ii, few studies have discovered and designed novel derivatives of COR, such as designed N -octanoylcordycepin which exhibits lower metabolic velocity and higher bioavailability than COR [139]. In strategy iii, appropriate region-targeted drug carriers, such as transferrin-conjugated liposomes for COR delivery to liver cancer cells [143] and gelatin type A nanoparticle for COR delivery to lung cancer cells [134], increase the specific accumulation of COR at the desired region, decrease the total dose of COR and reduce unintended extravasation into healthy regions.Overcoming drug resistance. Drug resistance presents a serious challenge when diseased cells develop resistance to COR over time through various mechanisms that markedly reduce the curative potency of COR.…”

Section: Pros and Cons Of Cor In Clinical Applicationsmentioning

confidence: 99%

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Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi

Qin

Yang

et al. 2019

Molecules

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Cordycepin (3′-deoxyadenosine), a cytotoxic nucleoside analogue found in Cordyceps militaris, has attracted much attention due to its therapeutic potential and biological value. Cordycepin interacts with multiple medicinal targets associated with cancer, tumor, inflammation, oxidant, polyadenylation of mRNA, etc. The investigation of the medicinal drug actions supports the discovery of novel targets and the development of new drugs to enhance the therapeutic potency and reduce toxicity. Cordycepin may be of great value owing to its medicinal potential as an external drug, such as in cosmeceutical, traumatic, antalgic and muscle strain applications. In addition, the biological application of cordycepin, for example, as a ligand, has been used to uncover molecular structures. Notably, studies that investigated the metabolic mechanisms of cordycepin-producing fungi have yielded significant information related to the biosynthesis of high levels of cordycepin. Here, we summarized the medicinal targets, biological applications, cytotoxicity, delivery carriers, stability, and pros/cons of cordycepin in clinical applications, as well as described the metabolic mechanisms of cordycepin in cordycepin-producing fungi. We posit that new approaches, including single-cell analysis, have the potential to enhance medicinal potency and unravel all facets of metabolic mechanisms of cordycepin in Cordyceps militaris.

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“…14 Further, conjugation of transferrin to these liposomes was found effective in the targeted delivery of cordycepin to liver cancer cells. 22 PLGA is a non-toxic, biodegradable and biocompatible polymer approved by FDA for drug delivery applications that has been extensively used in the encapsulation of drug molecules to enhance their clinical efficacy. PLGA consists of monomers of polylactic acid and polyglycolic acid, which degrade through hydrolysis but are resistant to enzymatic degradation.…”

Section: Introductionmentioning

confidence: 99%

<p>Cordycepin Nanoencapsulated in Poly(Lactic-Co-Glycolic Acid) Exhibits Better Cytotoxicity and Lower Hemotoxicity Than Free Drug</p>

Marslin¹,

Khandelwal²,

Franklin³

2020

NSA

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Purpose: Cordycepin, a natural product isolated from the fungus Cordyceps militaris, is a potential candidate for breast cancer therapy. However, due to its structural similarity with adenosine, cordycepin is rapidly metabolized into an inactive form in the body, hindering its development as a therapeutic agent. In the present study, we have prepared cordycepin as nanoparticles in poly(lactic-co-glycolic acid) (PLGA) and compared their cellular uptake, cytotoxicity and hemolytic potential with free cordycepin. Materials and Methods: Cordycepin-loaded PLGA nanoparticles (CPNPs) were prepared by the double-emulsion solvent evaporation method. Physico-chemical characterization of the nanoparticles was done by zetasizer, transmission electron microscopy (TEM) and reverse-phase high-pressure liquid chromatography (RP-HPLC) analyses. Cellular uptake and cytotoxicity of CPNPs and free drug were tested in human breast cancer cells (MCF7). Hemolytic potential of both of these forms was evaluated in rat red blood cells (RBCs). Results: Physico-chemical characterization revealed that CPNPs were spherical in shape, possessed a size range of 179-246 nm, and released the encapsulated drug sustainably over a period of 10 days. CPNPs exhibited a high level of cellular uptake and cytotoxicity than the free drug in MCF-7 cells. While CPNPs were not toxic to rat RBCs even at high concentrations, free cordycepin induced hemolysis of these cells at relatively low concentration. Conclusion: Our results reveal that delivery as CPNPs could enhance the clinical efficacy of cordycepin substantially.

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Targeted Delivery of Cordycepin to Liver Cancer Cells Using Transferrin-conjugated Liposomes

Abstract: Transferrin-conjugated liposomes are effective as nanocarriers for cordycepin delivery to liver cancer cells.

Cited by 14 publications

References 13 publications

Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution

Bufalin-Loaded PEGylated Liposomes: Antitumor Efficacy, Acute Toxicity, and Tissue Distribution

Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi

<p>Cordycepin Nanoencapsulated in Poly(Lactic-Co-Glycolic Acid) Exhibits Better Cytotoxicity and Lower Hemotoxicity Than Free Drug</p>

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