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Review
. 2015;10(16):2613-33.
doi: 10.2217/nnm.15.111. Epub 2015 Aug 5.

Nanoparticle-mediated drug delivery for treating melanoma

Vaibhav Mundra  1 , Wei Li  2 , Ram I Mahato  1
Affiliations
Review

Nanoparticle-mediated drug delivery for treating melanoma

Vaibhav Mundra et al. Nanomedicine (Lond). 2015.

Abstract

Melanoma originated from melanocytes is the most aggressive type of skin cancer with limited treatment options. New targeted therapeutic options with the discovery of BRAF and MEK inhibitors have shown significant survival benefits. Despite the recent progress, development of chemoresistance and systemic toxicity remains a challenge for treating metastatic melanoma. While the response from the first line of treatment against melanoma using dacarbazine remains only 5-10%, the prolonged use of targeted therapy against mutated oncogene BRAF develops chemoresistance. In this review, we will discuss the nanoparticle-based strategies for encapsulation and conjugation of drugs to the polymer for maximizing their tumor distribution through enhanced permeability and retention effect. We will also highlight photodynamic therapy and design of melanoma-targeted nanoparticles.

Keywords: active targeting; metastatic melanoma; multidrug resistance; nanoparticles; photodynamic therapy; polymer–drug conjugate; tumor initiating cells.

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Conflict of interest statement

Financial & competing interests disclosure This work is supported by NIH/NCI grant R01CA148706 to W Li. The authors also duly acknowledge the Buffett Cancer Center at the University of Nebraska Medical Center for financial support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Potential multidrug resistance mechanisms of metastatic melanoma.
Development of resistance in metastatic melanoma can be attributed to inefficient intracellular drug accumulation, upregulation of expression of class III β-tubulin, intracellular sequestration and compensatory upregulation of DNA repair pathways.
<b>Figure 2.</b>
Figure 2.. Nanoparticle-mediated drug delivery.
Poor extravasation of nanoparticles across endothelium of vital organs and enhanced permeability and retention of nanoparticles at tumor site result in preferential tumor distribution of chemotherapeutics. To harness full potential of nanoparticle-based drug delivery, Kr from nanoparticles should be much smaller as compared with Kd preventing premature release of drug from nanoparticles while in circulation. EPR: Enhanced permeability and retention; Kd: Distribution rate constant; Kr: Release rate constant.
<b>Figure 3.</b>
Figure 3.. Chemical structure of polymeric backbone used for formulation of polymer–drug conjugate-based nanoparticles.
Polyethylene glycol and N-(2 hydroxypropyl) methacrlyamide are nonbiodegradable. Polyglutamic acid contains degradable amide bond.
See this image and copyright information in PMC

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