Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, In Vitro Toxicity, and In Vivo Imaging Studies

Anbharasi Lakshmanan; Roman A Akasov; Natalya V Sholina; Polina A Demina; Alla N Generalova; Ajithkumar Gangadharan; Dhiraj K Sardar; Krishna Bharat Lankamsetty; Dmitry A Khochenkov; Evgeny V Khaydukov; Sergey V Gudkov; Manonmani Jayaraman; Senthilselvan Jayaraman

doi:10.3390/nano11092234

Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, In Vitro Toxicity, and In Vivo Imaging Studies

Nanomaterials (Basel). 2021 Aug 29;11(9):2234. doi: 10.3390/nano11092234.

Authors

Anbharasi Lakshmanan¹, Roman A Akasov^{2

3

4}, Natalya V Sholina^{2

3}, Polina A Demina⁴, Alla N Generalova^{3

4}, Ajithkumar Gangadharan^{5

6}, Dhiraj K Sardar^{5

6}, Krishna Bharat Lankamsetty⁷, Dmitry A Khochenkov^{8

9}, Evgeny V Khaydukov^{2

3}, Sergey V Gudkov^{10

11}, Manonmani Jayaraman¹², Senthilselvan Jayaraman¹

Affiliations

¹ Department of Nuclear Physics, Guindy Campus, University of Madras, Chennai 600025, Tamil Nadu, India.
² I M Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
³ Federal Scientific Research Center, "Crystallography and Photonics", Russian Academy of Sciences, Leninskiy Prospekt 59, 119333 Moscow, Russia.
⁴ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, 117997 Moscow, Russia.
⁵ Department of Physics and Astronomy, University of Texas at San Antonio, San Antonio, TX 78249, USA.
⁶ Department of Natural Sciences, Texas Agriculture and Mechanical University, One University Way, San Antonio, TX 78224, USA.
⁷ Federal State Budgetary Scientific Institution "Federal Scientific Agroengineering Center VIM" (FSAC VIM), 109428 Moscow, Russia.
⁸ FSBI "N.N. Blokhin National Medical Research Center for Oncology", Ministry of Health of the Russian Federation, Kashirskoe Shosse 24, 115478 Moscow, Russia.
⁹ Medicinal Chemistry Center, Togliatti State University, Belorusskaya Str. 14, 445020 Togliatti, Russia.
¹⁰ Biophotonics Center, Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilova St. 38, 119991 Moscow, Russia.
¹¹ Department of Closed Artificial Agroecosystems for Crop Production, Federal State Budgetary Scientific Institution "Federal Scientific Agroengineering Center VIM" (FSAC VIM), 5 First Institutskiy pr-d, 109428 Moscow, Russia.
¹² Department of Chemistry, Quaid-E-Millath Government College for Women, Chennai 600002, Tamil Nadu, India.

Abstract

Formulation of promising anticancer herbal drug curcumin as a nanoscale-sized curcumin (nanocurcumin) improved its delivery to cells and organisms both in vitro and in vivo. We report on coupling nanocurcumin with upconversion nanoparticles (UCNPs) using Poly (lactic-co-glycolic Acid) (PLGA) to endow visualisation in the near-infrared transparency window. Nanocurcumin was prepared by solvent-antisolvent method. NaYF₄:Yb,Er (UCNP1) and NaYF₄:Yb,Tm (UCNP2) nanoparticles were synthesised by reverse microemulsion method and then functionalized it with PLGA to form UCNP-PLGA nanocarrier followed up by loading with the solvent-antisolvent process synthesized herbal nanocurcumin. The UCNP samples were extensively characterised with XRD, Raman, FTIR, DSC, TGA, UV-VIS-NIR spectrophotometer, Upconversion spectrofluorometer, HRSEM, EDAX and Zeta Potential analyses. UCNP1-PLGA-nanocurcumin exhibited emission at 520, 540, 660 nm and UCNP2-PLGA-nanocurmin showed emission at 480 and 800 nm spectral bands. UCNP-PLGA-nanocurcumin incubated with rat glioblastoma cells demonstrated moderate cytotoxicity, 60-80% cell viability at 0.12-0.02 mg/mL marginally suitable for therapeutic applications. The cytotoxicity of UCNPs evaluated in tumour spheroids models confirmed UCNP-PLGA-nanocurcumin therapeutic potential. As-synthesised curcumin-loaded nanocomplexes were administered in tumour-bearing laboratory animals (Lewis lung cancer model) and showed adequate contrast to enable in vivo and ex vivo study of UCNP-PLGA-nanocurcumin bio distribution in organs, with dominant distribution in the liver and lungs. Our studies demonstrate promise of nanocurcumin-loaded upconversion nanoparticles for theranostics applications.

Keywords: herbal drugs; intravital imaging; nanocurcumin; theranostics; upconversion nanoparticles.

Abstract

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