International Journal of Nanomedicine (Oct 2024)

Delivery of Avocado Seed Extract Using Novel Charge-Switchable Mesoporous Silica Nanoparticles with Galactose Surface Modified to Target Sorafenib-Resistant Hepatocellular Carcinoma

  • Basu A,
  • Sae-be A,
  • Namporn T,
  • Suriyaphan O,
  • Sithisarn P,
  • Leanpolchareanchai J,
  • Plommaithong P,
  • Chatsukit A,
  • Sa-ngiamsuntorn K,
  • Naruphontjirakul P,
  • Ruenraroengsak P

Journal volume & issue
Vol. Volume 19
pp. 10341 – 10365

Abstract

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Aalok Basu,1 Arunsajee Sae-be,1 Thanaphon Namporn,1 Orasa Suriyaphan,2 Pongtip Sithisarn,3 Jiraporn Leanpolchareanchai,1 Piyaporn Plommaithong,1 Apichat Chatsukit,1 Khanit Sa-ngiamsuntorn,4 Parichart Naruphontjirakul,5 Pakatip Ruenraroengsak1,6 1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Department of Food Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 3Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 4Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 5Biological Engineering Program, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand; 6Centre of Molecular Targeting and Integrated Drug Development, Faculty of Pharmacy, Mahidol University, Bangkok, ThailandCorrespondence: Pakatip Ruenraroengsak, Division of Pharmaceutical Technology, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand, Email [email protected]: Sorafenib-resistant (SR) hepatocellular carcinoma (HCC) is a current serious problem in liver cancer treatment. Numerous phytochemicals derived from plants exhibit anticancer activity but have never been tested against drug-resistant cells.Methods: Avocado seed extract (APE) isolated by maceration was analysed for its phytochemical composition and anticancer activity. Novel design charge-switchable pH-responsive nanocarriers of aminated mesoporous silica nanoparticles with conjugated galactose (GMSN) were synthesised for delivering APE and their physicochemical properties were characterized. The drug loading efficiency (%LE) and entrapment efficiency (%EE) were evaluated. Anticancer activity of APE loaded GMSN was measured against HCC (HepG2, Huh-7) and SR-HCC (SR-HepG2).Results: Anticancer activity of APE against non-resistant HepG2 (IC50 50.9 ± 0.83 μg mL− 1), Huh-7 (IC50 42.41 ± 1.88 μg mL− 1), and SR-HepG2 (IC50 62.58 ± 2.29 μg mL− 1) cells was confirmed. The APE loaded GMSN had a diameter of 131.41 ± 14.41 nm with 41.08 ± 2.09%LE and 44.96 ± 2.26%EE. Galactose functionalization (55%) did not perturb the original mesoporous structure. The GMSN imparted positive surface charges, 10.3 ± 0.61mV at acidic medium pH 5.5 along with rapid release of APE 45% in 2 h. The GMSN boosted cellular uptake by HepG2 and SR-HepG2 cells, whereas the amine functionalized facilitated their endosomal escape. Their anticancer activity was demonstrated in non-resistant HCC and SR-HCC cells with IC50 values at 30.73 ± 3.14 (HepG2), 21.86 ± 0.83 (Huh-7), 35.64 ± 1.34 (SR-HepG2) μg mL− 1, respectively, in comparison to the control and non-encapsulated APE.Conclusion: APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further in vivo investigation. Keywords: liver cancer, hepatocellular carcinoma, galactose, sorafenib drug resistance, avocado, mesoporous silica nanoparticles

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