Engineering of peglayted camptothecin into core–shell nanomicelles for improving solubility, stability and combination delivery

Dong, Haiqing; Dong, Chunyan; Feng, Yue; Ren, Tianbin; Zhang, Zhonghai; Li, Lan; Li, Yongyong

doi:10.1039/c2md20153d

Cited by 18 publications

(5 citation statements)

References 25 publications

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“…However, the risk of inducing cardiomyopathy is not abated; the median cumulative dose of epirubicin to the development of symptomatic CHF is 1134 mg/m 2 [ 5 ]. Early studies found that encapsulation of doxorubicin inside liposomes decreases the cardiotoxicity associated with the free form of the drug, while maintaining anticancer potency [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Since the liposomal form of the drug is less toxic for the nondividing cells, increased drug dosages can be administered, ensuing in improved efficacy and an increase in the therapeutic index.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

Gumulec

Fojtů

Raudenská

et al. 2014

IJMS

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Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.

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Section: Introductionmentioning

confidence: 99%

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

Gumulec

Fojtů

Raudenská

et al. 2014

IJMS

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“…However, the clinical use of CPT is limited by its extremely hydrophobicity and low stability in vivo (Koo et al, 2005; Botella and Rivero-Buceta, 2017). A CPT-PEG-CPT prodrug has been prepared by conjugating two molecules of CPT to the ends of PEG via degradable ester linkage (Dong et al, 2012). This complex, which can accommodate CPT up to 41%, self-assembled into micelles with a diameter of 50 nm.…”

Section: Peg-derivatized Dual-functional Micelles With Intrinsic Antimentioning

confidence: 99%

PEG-Derivatized Dual-Functional Nanomicelles for Improved Cancer Therapy

Zhang

Liu

et al. 2019

Front. Pharmacol.

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Polymeric micelles have attracted considerable attention for effective delivery of poorly water-soluble cancer drugs. Polyethylene glycol (PEG), which has been approved for human use by the US Food and Drug Administration, is the most commonly used hydrophilic component of polymeric micelles because it is biocompatible and biodegradable. One disadvantage of traditional polymeric micelles is that they include a large amount of inert carrier materials, which do not contribute to therapeutic activity but increase cost and toxicity risk. A better alternative may be “dual-functional” micellar carriers, in which the hydrophobic carrier material (conjugated to PEG) has intrinsic therapeutic activity that complements, or even synergizes with, the antitumor activity of the drug cargo. This review summarizes recent progress in the development of PEG-derivatized dual-functional nanomicelles and surveys the evidence of their feasibility and promise for cancer therapy.

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“…Camptothecin (CPT), which originally isolated from the wood and bark of Camptotheca acuminatain, is a topoisomerase I poison that exhibits potent anticancer efficacy against a variety of tumors. − However, CPT is faced with limitations such as low aqueous solubility and high toxicity issues, restricting its clinical development in cancer treatment. − A number of approaches have been proposed to overcome these problems, ,− such as using macrocycles that can act as molecular container compounds. − Among these, cucurbit[ n ]urils (CB[ n ], n = 5, 6, 7, 8, 10), which are pumpkinlike molecular containers composed of glycoluril monomers linked by methylene bridges, have been developing rapidly. − Recently, Cheng et al reported the synthesis of a new cucurbituril homologue, named twisted Q[14], tQ[14], which has 14 units of −glycoluril-(CH2)2– moiety with a twisted structure . CB[ n ]s have a rigid structure containing a hydrophobic cavity and hydrophilic carbonyl-fringed portals. − The utility of these macrocycles has been significantly revealed in the wide range of exciting applications including catalysis, molecular recognition, molecular machines, biomedicine, rotaxanes, pseudorotaxanes, and drug delivery vehicle. ,,,, For example, Dong et al used CB[7] and CB[8] to improve the solubility properties of CPT and showed that the solubility of CPT increased up to 70 and 8 times for the CPT@CB[7] and CPT@CB[8] complexes, respectively (pH = 2).…”

Section: Introductionmentioning

confidence: 99%

Molecular Insight into the Interaction between Camptothecin and Acyclic Cucurbit[4]urils as Efficient Nanocontainers in Comparison with Cucurbit[7]uril: Molecular Docking and Molecular Dynamics Simulation

Ahmadian

Mehrnejad

Amininasab

2020

J. Chem. Inf. Model.

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Cucurbit[n]urils (CB[n], n = 5, 6, 7, 8, 10, 14) and their derivatives due to the hydrophobic cavities and polar carbonyl portals have been considerably explored for their potential uses as drug delivery systems. It is important to understand how these macrocyclic compounds interact with guests. Camptothecin (CPT), as a natural alkaloid, is a topoisomerase inhibitor with antitumor activity against breast, pancreas, and lung cancers. The application of this drug in cancer therapy is restricted due to its low aqueous solubility and high toxicity. Recently, the complex formation between the cucurbit[7]uril (CB[7])/acyclic cucurbit[4]uril (aCB[4]) nanocontainers and CPT have been evaluated to overcome the potential drawbacks of the related drug. Herein, using computational methods, we identified the interaction mechanism of CPT with CB[7]/aCB[4]s, which consist of benzene and naphthalene sidewalls (aCB[4]benzene and aCB[4]naphthalene, respectively) since the experimental approaches have not completely provided information at the molecular level. Our molecular docking and molecular dynamics (MD) simulations show that CB[7] and its two acyclic derivatives form stable inclusion complexes with CPT especially through hydrophobic interactions. We also found that aCB[4]s with the aromatic sidewalls can attach to CPT through π–π interactions. This investigation highlights aCB[4]s due to the structural properties and flexible nature as better nanocontainers for controlled release delivery of pharmaceutical agents in comparison with the CB[7] nanocontainer.

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Engineering of peglayted camptothecin into core–shell nanomicelles for improving solubility, stability and combination delivery

Cited by 18 publications

References 25 publications

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

PEG-Derivatized Dual-Functional Nanomicelles for Improved Cancer Therapy

Molecular Insight into the Interaction between Camptothecin and Acyclic Cucurbit[4]urils as Efficient Nanocontainers in Comparison with Cucurbit[7]uril: Molecular Docking and Molecular Dynamics Simulation

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