Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors

Biki Gupta; Thiruganesh Ramasamy; Bijay Kumar Poudel; Shiva Pathak; Shobha Regmi; Ju Yeon Choi; Youlim Son; Raj Kumar Thapa; Jee Heon Jeong; Jae Ryong Kim; Han Gon Choi; Chul Soon Yong; Jong Oh Kim

doi:10.1021/acsami.6b09163

Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors

Biki Gupta, Thiruganesh Ramasamy, Bijay Kumar Poudel, Shiva Pathak, Shobha Regmi, Ju Yeon Choi, Youlim Son, Raj Kumar Thapa, Jee Heon Jeong, Jae Ryong Kim, Han Gon Choi, Chul Soon Yong, Jong Oh Kim

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro. DOX/IMT-N significantly inhibited the in vitro proliferation of MDA-MB-231 and SK-MEL-28 cells. The inhibitory effect on in vitro proliferation of the cells was significantly greater than the effect of free DOX, DOX/IMT cocktail, or the nanostructured system housing DOX only (DOX-N). DOX/IMT-N remarkably enhanced cellular drug uptake, resulting in enhanced apoptosis, caused by significant increases in the expression levels of apoptotic marker proteins. Intravenous administration of DOX/IMT-N to MBA-MB-231 xenograft tumor-bearing mice resulted in significantly improved inhibition of tumor progression compared to that with DOX, DOX/IMT, or DOX-N. Therefore, the nanostructured DOX/IMT-N system could potentially aid in overcoming drug resistance in metastatic tumors and improve the effectiveness of metastatic tumor therapeutics.

Original language	English
Pages (from-to)	9280-9290
Number of pages	11
Journal	ACS Applied Materials and Interfaces
Volume	9
Issue number	11
DOIs	https://doi.org/10.1021/acsami.6b09163
State	Published - 22 Mar 2017
Externally published	Yes

Keywords

chemoresistance
doxorubicin
drug delivery
imatinib
metastasis
nanostructured platform

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsami.6b09163

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Gupta, B., Ramasamy, T., Poudel, B. K., Pathak, S., Regmi, S., Choi, J. Y., Son, Y., Thapa, R. K., Jeong, J. H., Kim, J. R., Choi, H. G., Yong, C. S., & Kim, J. O. (2017). Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors. ACS Applied Materials and Interfaces, 9(11), 9280-9290. https://doi.org/10.1021/acsami.6b09163

@article{7700f1e390a04d1881a696fbd2698969,

title = "Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors",

abstract = "Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro. DOX/IMT-N significantly inhibited the in vitro proliferation of MDA-MB-231 and SK-MEL-28 cells. The inhibitory effect on in vitro proliferation of the cells was significantly greater than the effect of free DOX, DOX/IMT cocktail, or the nanostructured system housing DOX only (DOX-N). DOX/IMT-N remarkably enhanced cellular drug uptake, resulting in enhanced apoptosis, caused by significant increases in the expression levels of apoptotic marker proteins. Intravenous administration of DOX/IMT-N to MBA-MB-231 xenograft tumor-bearing mice resulted in significantly improved inhibition of tumor progression compared to that with DOX, DOX/IMT, or DOX-N. Therefore, the nanostructured DOX/IMT-N system could potentially aid in overcoming drug resistance in metastatic tumors and improve the effectiveness of metastatic tumor therapeutics.",

keywords = "chemoresistance, doxorubicin, drug delivery, imatinib, metastasis, nanostructured platform",

author = "Biki Gupta and Thiruganesh Ramasamy and Poudel, \{Bijay Kumar\} and Shiva Pathak and Shobha Regmi and Choi, \{Ju Yeon\} and Youlim Son and Thapa, \{Raj Kumar\} and Jeong, \{Jee Heon\} and Kim, \{Jae Ryong\} and Choi, \{Han Gon\} and Yong, \{Chul Soon\} and Kim, \{Jong Oh\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

month = mar,

day = "22",

doi = "10.1021/acsami.6b09163",

language = "English",

volume = "9",

pages = "9280--9290",

journal = "ACS Applied Materials and Interfaces",

issn = "1944-8244",

publisher = "American Chemical Society",

number = "11",

}

Gupta, B, Ramasamy, T, Poudel, BK, Pathak, S, Regmi, S, Choi, JY, Son, Y, Thapa, RK, Jeong, JH, Kim, JR, Choi, HG, Yong, CS & Kim, JO 2017, 'Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors', ACS Applied Materials and Interfaces, vol. 9, no. 11, pp. 9280-9290. https://doi.org/10.1021/acsami.6b09163

Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors. / Gupta, Biki; Ramasamy, Thiruganesh; Poudel, Bijay Kumar et al.
In: ACS Applied Materials and Interfaces, Vol. 9, No. 11, 22.03.2017, p. 9280-9290.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors

AU - Gupta, Biki

AU - Ramasamy, Thiruganesh

AU - Poudel, Bijay Kumar

AU - Pathak, Shiva

AU - Regmi, Shobha

AU - Choi, Ju Yeon

AU - Son, Youlim

AU - Thapa, Raj Kumar

AU - Jeong, Jee Heon

AU - Kim, Jae Ryong

AU - Choi, Han Gon

AU - Yong, Chul Soon

AU - Kim, Jong Oh

PY - 2017/3/22

Y1 - 2017/3/22

N2 - Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro. DOX/IMT-N significantly inhibited the in vitro proliferation of MDA-MB-231 and SK-MEL-28 cells. The inhibitory effect on in vitro proliferation of the cells was significantly greater than the effect of free DOX, DOX/IMT cocktail, or the nanostructured system housing DOX only (DOX-N). DOX/IMT-N remarkably enhanced cellular drug uptake, resulting in enhanced apoptosis, caused by significant increases in the expression levels of apoptotic marker proteins. Intravenous administration of DOX/IMT-N to MBA-MB-231 xenograft tumor-bearing mice resulted in significantly improved inhibition of tumor progression compared to that with DOX, DOX/IMT, or DOX-N. Therefore, the nanostructured DOX/IMT-N system could potentially aid in overcoming drug resistance in metastatic tumors and improve the effectiveness of metastatic tumor therapeutics.

AB - Metastasis of cancers accounts for almost all cancer-related deaths. In this study, we report a PEGylated nanostructured platform for coadministration of doxorubicin (DOX) and imatinib (IMT) intended to effectively inhibit metastatic tumors. The DOX and IMT coloaded nanostructured system (DOX/IMT-N) is characterized by an excellent encapsulation potential for both drugs and shows sequential and sustained drug release in vitro. DOX/IMT-N significantly inhibited the in vitro proliferation of MDA-MB-231 and SK-MEL-28 cells. The inhibitory effect on in vitro proliferation of the cells was significantly greater than the effect of free DOX, DOX/IMT cocktail, or the nanostructured system housing DOX only (DOX-N). DOX/IMT-N remarkably enhanced cellular drug uptake, resulting in enhanced apoptosis, caused by significant increases in the expression levels of apoptotic marker proteins. Intravenous administration of DOX/IMT-N to MBA-MB-231 xenograft tumor-bearing mice resulted in significantly improved inhibition of tumor progression compared to that with DOX, DOX/IMT, or DOX-N. Therefore, the nanostructured DOX/IMT-N system could potentially aid in overcoming drug resistance in metastatic tumors and improve the effectiveness of metastatic tumor therapeutics.

KW - chemoresistance

KW - doxorubicin

KW - drug delivery

KW - imatinib

KW - metastasis

KW - nanostructured platform

UR - https://www.scopus.com/pages/publications/85016006338

U2 - 10.1021/acsami.6b09163

DO - 10.1021/acsami.6b09163

M3 - Article

C2 - 28240860

AN - SCOPUS:85016006338

SN - 1944-8244

VL - 9

SP - 9280

EP - 9290

JO - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

IS - 11

ER -

Development of Bioactive PEGylated Nanostructured Platforms for Sequential Delivery of Doxorubicin and Imatinib to Overcome Drug Resistance in Metastatic Tumors

Abstract

Keywords

UN SDGs

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