Multifunctional particles for melanoma-targeted drug delivery

Aniket S. Wadajkar; Zarna Bhavsar; Cheng Yu Ko; Bhanuprasanth Koppolu; Weina Cui; Liping Tang; Kytai T. Nguyen

doi:10.1016/j.actbio.2012.04.042

Multifunctional particles for melanoma-targeted drug delivery

Aniket S. Wadajkar, Zarna Bhavsar, Cheng Yu Ko, Bhanuprasanth Koppolu, Weina Cui, Liping Tang, Kytai T. Nguyen

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

76 Scopus citations

Abstract

New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N- isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the ^α5β3 receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml^-1. Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.

Original language	English (US)
Pages (from-to)	2996-3004
Number of pages	9
Journal	Acta Biomaterialia
Volume	8
Issue number	8
DOIs	https://doi.org/10.1016/j.actbio.2012.04.042
State	Published - Aug 2012
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank Vikrant Sharma for help with the MR image analysis. TEM was performed at the Molecular and Cellular Imaging Facility at the University of Texas Southwestern Medical Center at Dallas, TX. This work was partially supported by NIH grant EB007271 (L.T.) and DOD grant W81XWH-09-1-0313 (K.N.).

Keywords

Biodegradable polymers
Magnetite nanoparticles
Melanoma
Targeted drug delivery
Thermo-responsive polymers

UN SDGs

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

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title = "Multifunctional particles for melanoma-targeted drug delivery",

abstract = "New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N- isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α5β3 receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 μg ml-1. Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.",

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note = "Funding Information: The authors thank Vikrant Sharma for help with the MR image analysis. TEM was performed at the Molecular and Cellular Imaging Facility at the University of Texas Southwestern Medical Center at Dallas, TX. This work was partially supported by NIH grant EB007271 (L.T.) and DOD grant W81XWH-09-1-0313 (K.N.). ",

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AU - Bhavsar, Zarna

AU - Ko, Cheng Yu

AU - Koppolu, Bhanuprasanth

AU - Cui, Weina

AU - Tang, Liping

AU - Nguyen, Kytai T.

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Multifunctional particles for melanoma-targeted drug delivery

Abstract

Bibliographical note

Keywords

UN SDGs

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