Dual Encapsulated Dacarbazine and Zinc Phthalocyanine Polymeric Nanoparticle for Photodynamic Therapy of Melanoma

Abstract

Purpose

Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments.

Methods

PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs.

Results

The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced.

Conclusion

This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.

Graphical abstract

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Abbreviations

99mTc:

Technetium 99 metastable

AFM:

Atomic force microscopy

DITC:

Dacarbazine

DLS:

Dynamic light scattering

DMSO:

Dimethyl sulfoxide

EDTA:

Ethylenediaminetetraacetic acid

MBq:

Mega-Becquerel

MTT:

(3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide)

MV3:

Melanoma cell line

NP:

Nanoparticle

NPs:

Nanoparticles

PDT:

Photodynamic therapy

PLA:

Poly lactic acid

PVA:

Polyvinyl alcohol

RTLC:

Radio thin layer chromatography

ZnPc:

Zinc phthalocyanine

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Correspondence to Ralph Santos-Oliveira.

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do Reis, S.R.R., Helal-Neto, E., da Silva de Barros, A.O. et al. Dual Encapsulated Dacarbazine and Zinc Phthalocyanine Polymeric Nanoparticle for Photodynamic Therapy of Melanoma. Pharm Res 38, 335–346 (2021). https://doi.org/10.1007/s11095-021-02999-w

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Key Words

  • dacarbazine
  • drug resistance
  • melanoma
  • nanoparticle
  • photodynamic therapy