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Simultaneous Delivery of Chemotherapeutic and Thermal-Optical Agents to Cancer Cells by a Polymeric (PLGA) Nanocarrier: An In Vitro Study

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ABSTRACT

Purpose

To test the effectiveness of a dual–agent-loaded PLGA nanoparticulate drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in a DOX-sensitive cell line and two resistant cell lines that have different resistance mechanisms.

Methods

The DOX-sensitive MES-SA uterine sarcoma cell line was used as a negative control. The two resistant cell lines were uterine sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P-glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to doxorubicin due to a p53 gene mutation. The cellular uptake, subcellular localization and cytotoxicity of the two agents when delivered via nanoparticles (NPs) were compared to their free-form administration.

Results

The cellular uptake and cytotoxicity of DOX delivered by NPs were comparable to the free form in MES-SA and SKOV-3, but much higher in MES-SA/Dx5, indicating the capability of the NPs to overcome P-glycoprotein resistance mechanisms. NP-encapsulated ICG showed slightly different subcellular localization, but similar fluorescence intensity when compared to free ICG, and retained the ability to generate heat for hyperthermia delivery.

Conclusion

The dual-agent-loaded system allowed for the simultaneous delivery of hyperthermia and chemotherapy, and this combinational treatment greatly improved cytotoxicity in MES-SA/Dx5 cells and to a lesser extent in SKOV-3 cells.

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Abbreviations

DOX:

Doxorubicin

ICG:

Indocyanine green

MDR:

Multidrug resistance

P-gp:

P-glycoprotein

NIR:

Near-infrared

NP:

Nanoparticle

PLGA:

Poly (DL-lactide-co-glycolide)

DMSO:

Dimethylsulfoxide

PVA:

Polyvinyl alcohol

DCM:

Dichloromethane

ICG-DOX-PLGANPs:

Poly (DL-lactide-co-glycolide) NPs loaded with indocyanine green and doxorubicin

DLS:

Dynamic light scattering

SEM:

Scanning electron microscopy

Dx5:

MES-SA/Dx5

FBS:

Fetal bovine serum

ICG-DOX:

Nonencapsulated DOX and ICG mixture solution

DPBS:

Dulbecco’s Phosphate Buffered Saline

NPC:

Nuclear pore complex

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ACKNOWLEDGEMENTS

This work was conducted using the facilities of the Biomedical Engineering Department at Florida International University and partially funded by FLDOH (Grant #08-BB-11), the Biomedical Engineering Young Inventor Award from the Wallace H. Coulter Foundation to R.M., the Florida International University Dissertation Year Fellowship to Y.T., and support from NIH/NIGMS R25 GM061347 to A.F.F.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Florida International University, 10555 West Flagler Street, Miami, Florida, 33174, USA

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

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  1. Yuan Tang
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  2. Tingjun Lei
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  3. Romila Manchanda
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  7. Anthony J. McGoron
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Correspondence to Anthony J. McGoron.

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Tang, Y., Lei, T., Manchanda, R. et al. Simultaneous Delivery of Chemotherapeutic and Thermal-Optical Agents to Cancer Cells by a Polymeric (PLGA) Nanocarrier: An In Vitro Study. Pharm Res 27, 2242–2253 (2010). https://doi.org/10.1007/s11095-010-0231-6

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