Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

Authors Li X, Li H, Yi W, Chen J, Liang B

Received 26 March 2013

Accepted for publication 15 May 2013

Published 12 August 2013 Volume 2013:8(1) Pages 3019—3031

DOI https://doi.org/10.2147/IJN.S45767

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Xian Li,1,* Hao Li,2,4,* Wei Yi,3 Jianyu Chen,1 Biling Liang1

1Radiology Department, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China; 3Radiotherapy Department, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China; 4School of Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China

*These authors contributed equally to this work

Purpose: To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells.
Methods: As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results.
Results: To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced.
Conclusion: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.

Keywords: acid-triggered, DOX, nanomicelle carrier, folate-targeted effect, SPIONs

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Acquired hemophilia A: emerging treatment options

Janbain M, Leissinger CA, Kruse-Jarres R

Journal of Blood Medicine 2015, 6:143-150

Published Date: 8 May 2015

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

Second case report of successful electroconvulsive therapy for a patient with schizophrenia and severe hemophilia A

Saito N, Shioda K, Nisijima K, Kobayashi T, Kato S

Neuropsychiatric Disease and Treatment 2014, 10:865-867

Published Date: 16 May 2014

Rituximab for managing acquired hemophilia A in a case of chronic neutrophilic leukemia with the JAK2 kinase V617F mutation

Imashuku S, Kudo N, Kubo K, Saigo K, Okuno N, Tohyama K

Journal of Blood Medicine 2012, 3:157-161

Published Date: 5 December 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010