Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines

Tingjun Lei; Supriya Srinivasan; Yuan Tang; Romila Manchanda; Alicia Fernandez-Fernandez; Anthony J. McGoron

doi:10.1007/978-3-642-14998-6_57

Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines

Tingjun Lei
, Supriya Srinivasan
, Yuan Tang
, Romila Manchanda
, Alicia Fernandez-Fernandez
, Anthony J. McGoron

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

Doxorubicin (DOX) is an anthracycline drug widely used in the treatment of a large spectrum of solid tumors. Its application is limited by its efflux through the multidrug resistance (MDR) protein. In this study, we explored the potential of DOX - PLGA nanoparticles (DNPs) and antibody decorated nanoparticles (ADNPs) to overcome MDR in cancer cells. DNPs were prepared by the O/W emulsion solvent evaporation method. The surface decoration of nanoparticles with antibody was performed via carbodiimide reaction. The particles were characterized for their size and zeta potential, and their in vitro uptake was compared with their unconjugated counterparts. Entrapment efficiency of DNPs and ADNPs was measured by fluorescence using the DMSO burst release procedure. Cytotoxicity was measured using the SRB assay. The DNP and ADNP nanoparticles had average diameter of 162.6 ± 2.0 nm and 213.0 ± 3.5 nm respectively. Their corresponding surface charges were -13.2 ± 2.3 mV and -1.3 ± 3.8 mV respectively. Our results showed that cellular uptake of DOX from DNPs in DOX-resistant MES-SA/Dx5 cancer cell was higher compared to free DOX. However, the uptake of DOX from DNPs in MES-SA and SKOV-3 cancer cell lines was comparable to free DOX treatment. Next, we conjugated the DNPs with HER-2 antibody to specifically target to SKOV-3 cancer cell line and MES-SA and MES-SA/Dx5 were used as negative controls. Results showed higher uptake of DOX from ADNPs compared to free DOX and DNPs in SKOV-3. However, the cellular uptake of DOX from ADNPs was comparable to DNPs in MES-SA and MES-SA/Dx5. Cytotoxicity results were consistent with the cellular uptake data. Our study concludes that the targeted DNPs may enhance the cellular uptake and cytotoxicity in SKOV-3.

Original language	English
Title of host publication	26th Southern Biomedical Engineering Conference SBEC 2010
Pages	224-227
Number of pages	4
DOIs	https://doi.org/10.1007/978-3-642-14998-6_57
State	Published - 2010
Externally published	Yes
Event	26th Southern Biomedical Engineering Conference, SBEC 2010 - College Park, MD, United States Duration: Apr 30 2010 → May 2 2010

Publication series

Name	IFMBE Proceedings
Volume	32 IFMBE
ISSN (Print)	1680-0737

Conference

Conference	26th Southern Biomedical Engineering Conference, SBEC 2010
Country/Territory	United States
City	College Park, MD
Period	4/30/10 → 5/2/10

ASJC Scopus Subject Areas

Bioengineering
Biomedical Engineering

Keywords

Cellular uptake
Cytotoxicity
Doxorubicin
HER-2 antibody
PLGA

Access to Document

10.1007/978-3-642-14998-6_57

Cite this

Lei, T, Srinivasan, S, Tang, Y, Manchanda, R, Fernandez-Fernandez, A & McGoron, AJ 2010, Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines. in 26th Southern Biomedical Engineering Conference SBEC 2010. IFMBE Proceedings, vol. 32 IFMBE, pp. 224-227, 26th Southern Biomedical Engineering Conference, SBEC 2010, College Park, MD, United States, 4/30/10. https://doi.org/10.1007/978-3-642-14998-6_57

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title = "Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines",

abstract = "Doxorubicin (DOX) is an anthracycline drug widely used in the treatment of a large spectrum of solid tumors. Its application is limited by its efflux through the multidrug resistance (MDR) protein. In this study, we explored the potential of DOX - PLGA nanoparticles (DNPs) and antibody decorated nanoparticles (ADNPs) to overcome MDR in cancer cells. DNPs were prepared by the O/W emulsion solvent evaporation method. The surface decoration of nanoparticles with antibody was performed via carbodiimide reaction. The particles were characterized for their size and zeta potential, and their in vitro uptake was compared with their unconjugated counterparts. Entrapment efficiency of DNPs and ADNPs was measured by fluorescence using the DMSO burst release procedure. Cytotoxicity was measured using the SRB assay. The DNP and ADNP nanoparticles had average diameter of 162.6 ± 2.0 nm and 213.0 ± 3.5 nm respectively. Their corresponding surface charges were -13.2 ± 2.3 mV and -1.3 ± 3.8 mV respectively. Our results showed that cellular uptake of DOX from DNPs in DOX-resistant MES-SA/Dx5 cancer cell was higher compared to free DOX. However, the uptake of DOX from DNPs in MES-SA and SKOV-3 cancer cell lines was comparable to free DOX treatment. Next, we conjugated the DNPs with HER-2 antibody to specifically target to SKOV-3 cancer cell line and MES-SA and MES-SA/Dx5 were used as negative controls. Results showed higher uptake of DOX from ADNPs compared to free DOX and DNPs in SKOV-3. However, the cellular uptake of DOX from ADNPs was comparable to DNPs in MES-SA and MES-SA/Dx5. Cytotoxicity results were consistent with the cellular uptake data. Our study concludes that the targeted DNPs may enhance the cellular uptake and cytotoxicity in SKOV-3.",

keywords = "Cellular uptake, Cytotoxicity, Doxorubicin, HER-2 antibody, PLGA",

author = "Tingjun Lei and Supriya Srinivasan and Yuan Tang and Romila Manchanda and Alicia Fernandez-Fernandez and McGoron, \{Anthony J.\}",

year = "2010",

doi = "10.1007/978-3-642-14998-6\_57",

language = "English",

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TY - GEN

T1 - Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines

AU - Lei, Tingjun

AU - Srinivasan, Supriya

AU - Tang, Yuan

AU - Manchanda, Romila

AU - Fernandez-Fernandez, Alicia

AU - McGoron, Anthony J.

PY - 2010

Y1 - 2010

N2 - Doxorubicin (DOX) is an anthracycline drug widely used in the treatment of a large spectrum of solid tumors. Its application is limited by its efflux through the multidrug resistance (MDR) protein. In this study, we explored the potential of DOX - PLGA nanoparticles (DNPs) and antibody decorated nanoparticles (ADNPs) to overcome MDR in cancer cells. DNPs were prepared by the O/W emulsion solvent evaporation method. The surface decoration of nanoparticles with antibody was performed via carbodiimide reaction. The particles were characterized for their size and zeta potential, and their in vitro uptake was compared with their unconjugated counterparts. Entrapment efficiency of DNPs and ADNPs was measured by fluorescence using the DMSO burst release procedure. Cytotoxicity was measured using the SRB assay. The DNP and ADNP nanoparticles had average diameter of 162.6 ± 2.0 nm and 213.0 ± 3.5 nm respectively. Their corresponding surface charges were -13.2 ± 2.3 mV and -1.3 ± 3.8 mV respectively. Our results showed that cellular uptake of DOX from DNPs in DOX-resistant MES-SA/Dx5 cancer cell was higher compared to free DOX. However, the uptake of DOX from DNPs in MES-SA and SKOV-3 cancer cell lines was comparable to free DOX treatment. Next, we conjugated the DNPs with HER-2 antibody to specifically target to SKOV-3 cancer cell line and MES-SA and MES-SA/Dx5 were used as negative controls. Results showed higher uptake of DOX from ADNPs compared to free DOX and DNPs in SKOV-3. However, the cellular uptake of DOX from ADNPs was comparable to DNPs in MES-SA and MES-SA/Dx5. Cytotoxicity results were consistent with the cellular uptake data. Our study concludes that the targeted DNPs may enhance the cellular uptake and cytotoxicity in SKOV-3.

AB - Doxorubicin (DOX) is an anthracycline drug widely used in the treatment of a large spectrum of solid tumors. Its application is limited by its efflux through the multidrug resistance (MDR) protein. In this study, we explored the potential of DOX - PLGA nanoparticles (DNPs) and antibody decorated nanoparticles (ADNPs) to overcome MDR in cancer cells. DNPs were prepared by the O/W emulsion solvent evaporation method. The surface decoration of nanoparticles with antibody was performed via carbodiimide reaction. The particles were characterized for their size and zeta potential, and their in vitro uptake was compared with their unconjugated counterparts. Entrapment efficiency of DNPs and ADNPs was measured by fluorescence using the DMSO burst release procedure. Cytotoxicity was measured using the SRB assay. The DNP and ADNP nanoparticles had average diameter of 162.6 ± 2.0 nm and 213.0 ± 3.5 nm respectively. Their corresponding surface charges were -13.2 ± 2.3 mV and -1.3 ± 3.8 mV respectively. Our results showed that cellular uptake of DOX from DNPs in DOX-resistant MES-SA/Dx5 cancer cell was higher compared to free DOX. However, the uptake of DOX from DNPs in MES-SA and SKOV-3 cancer cell lines was comparable to free DOX treatment. Next, we conjugated the DNPs with HER-2 antibody to specifically target to SKOV-3 cancer cell line and MES-SA and MES-SA/Dx5 were used as negative controls. Results showed higher uptake of DOX from ADNPs compared to free DOX and DNPs in SKOV-3. However, the cellular uptake of DOX from ADNPs was comparable to DNPs in MES-SA and MES-SA/Dx5. Cytotoxicity results were consistent with the cellular uptake data. Our study concludes that the targeted DNPs may enhance the cellular uptake and cytotoxicity in SKOV-3.

KW - Cellular uptake

KW - Cytotoxicity

KW - Doxorubicin

KW - HER-2 antibody

KW - PLGA

UR - https://www.scopus.com/pages/publications/78049360406

UR - https://www.scopus.com/pages/publications/78049360406#tab=citedBy

U2 - 10.1007/978-3-642-14998-6_57

DO - 10.1007/978-3-642-14998-6_57

M3 - Conference contribution

AN - SCOPUS:78049360406

SN - 9783642149979

T3 - IFMBE Proceedings

SP - 224

EP - 227

BT - 26th Southern Biomedical Engineering Conference SBEC 2010

T2 - 26th Southern Biomedical Engineering Conference, SBEC 2010

Y2 - 30 April 2010 through 2 May 2010

ER -

Targeted delivery of doxorubicin by PLGA nanoparticles increases drug uptake in cancer cell lines

Abstract

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Keywords

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