Hyaluronic Acid-Poly(Lactic-Co-Glycolic Acid) Nanoparticles with a Ruthenium Photosensitizer Cargo for Photokilling of Oral Cancer Cells

36 Pages Posted: 8 Jun 2022

See all articles by jose Quilez Alburquerque

jose Quilez Alburquerque

Complutense University of Madrid

Mohammad Ahsan Saad

Harvard University - Harvard Medical School

Ana B. Descalzo

Complutense University of Madrid

Guillermo Orellana

Complutense University of Madrid

Tayyaba Hasan

Harvard University - Harvard Medical School

Abstract

Photodynamic therapy (PDT), a combination of light, molecular oxygen and a photosensitizing dye, has gained attention as a promising technique to treat various types of cancers. Among all the photosensitizers reported so far, ruthenium(II) polypyridyl complexes exhibit unique photophysical and photobiological features owing to their photostability, ms triplet excited states, and ability to undergo both ‘type I’ and ‘type II’ reactions in their photodynamic action. We report the synthesis a novel Ru(II) complex containing one 2,2'-biimidazole (bim) and two tetramethylphenanthroline (tmp) ligands that sensitizes the simultaneous production of superoxide anion (O 2 · - ) and singlet oxygen ( 1 O 2 ) upon irradiation with blue-green light. To improve its solubility and bioavailability, a zero-order degradation-controlled release formulation based on self-assembled hyaluronic acid (HA)–poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was prepared for its topical application in oral cancer cells (TR146 cell line). These NPs (152 nm diameter) showed 70% Ru-complex encapsulation efficiency, high physiological stability, low polydispersity index (0.12), and a sensitizer release enhanced by the hyaluronidase enzyme overexpressed in many cancer cells. Both the free complex and its nanocarrier are internalized by the TR146 cells, displaying >90% in vitro cytotoxicity under 470 nm activation (50 J cm⁻ 2 ), highlighting their potential as PDT agents. As hypoxia associated with oral and other cancers is a major barrier to photodynamic therapy which is being clinically employed for oral cancer management, the Ru(II) complex loaded nanocarrier developed in this study can be effective in the treatment of  early stage oral cancers and disinfection of wounds where light penetration is not a pre-requisite.

Keywords: Photodynamic therapy, Ru(II) complex, hyaluronic acid-poly(lactic-co-glycolic acid), superoxide anion

Suggested Citation

Quilez Alburquerque, jose and Saad, Mohammad Ahsan and Descalzo, Ana B. and Orellana, Guillermo and Hasan, Tayyaba, Hyaluronic Acid-Poly(Lactic-Co-Glycolic Acid) Nanoparticles with a Ruthenium Photosensitizer Cargo for Photokilling of Oral Cancer Cells. Available at SSRN: https://ssrn.com/abstract=4131246 or http://dx.doi.org/10.2139/ssrn.4131246

Jose Quilez Alburquerque

Complutense University of Madrid ( email )

Spain

Mohammad Ahsan Saad

Harvard University - Harvard Medical School ( email )

25 Shattuck St
Boston, MA 02115
United States

Ana B. Descalzo

Complutense University of Madrid ( email )

Spain

Guillermo Orellana

Complutense University of Madrid ( email )

Spain

Tayyaba Hasan (Contact Author)

Harvard University - Harvard Medical School ( email )

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