Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Apr 23

PMID 35456602

Authors

Ying-Hsia Shih

Cheng-Liang Peng

Ping-Fang Chiang

Ming-Jium Shieh

Affiliations

Soon will be listed here.

Abstract

The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake in HCT-116 cells. Then, subcutaneous HCT-116 xenograft tumors were used for ex vivo biodistribution, antitumor efficacy, and histochemical analysis studies. Results of cellular uptake and ex vivo biodistribution of SN-38/Sunitinib micelles showed the highest accumulation in tumors compared with other normal organs. In the antitumor effect studies, mice bearing HCT-116 tumors were smallest at day 28 after injection of SN-38/Sunitinib micelles, compared with other experiment groups (p < 0.01). As demonstrated by the results of inhibition on multi-receptors by Sunitinib, we confirmed that SN-38/Sunitinib co-loaded micelles to be a treatment modality that could inhibit VEGF and PDGF receptors and enhance the antitumor effect of SN-38 (p < 0.05). In summary, we consider that this micelle is a potential formulation for the combination of SN-38 and Sunitinib in the treatment of colorectal cancer.

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References

Laraib U, Sargazi S, Rahdar A, Khatami M, Pandey S . Nanotechnology-based approaches for effective detection of tumor markers: A comprehensive state-of-the-art review. Int J Biol Macromol. 2021; 195:356-383. DOI: 10.1016/j.ijbiomac.2021.12.052. View

Liu Y, Piao H, Gao Y, Xu C, Tian Y, Wang L . Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity. Int J Nanomedicine. 2015; 10:2295-311. PMC: 4376263. DOI: 10.2147/IJN.S77957. View

Li M, Xu Y, Lu W, Li Y, Tan S, Lin H . Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis. Oncol Lett. 2018; 15(3):2839-2846. PMC: 5778883. DOI: 10.3892/ol.2017.7635. View

Martino E, Volpe S, Terribile E, Benetti E, Sakaj M, Centamore A . The long story of camptothecin: From traditional medicine to drugs. Bioorg Med Chem Lett. 2017; 27(4):701-707. DOI: 10.1016/j.bmcl.2016.12.085. View

Mahmoudi Saber M, Bahrainian S, Dinarvand R, Atyabi F . Targeted drug delivery of Sunitinib Malate to tumor blood vessels by cRGD-chiotosan-gold nanoparticles. Int J Pharm. 2016; 517(1-2):269-278. DOI: 10.1016/j.ijpharm.2016.12.016. View

Mollica A, Stefanucci A, Feliciani F, Cacciatore I, Cornacchia C, Pinnen F . Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer. Curr Drug Deliv. 2012; 9(2):122-31. DOI: 10.2174/156720112800234558. View

Mahar A, Compton C, Halabi S, Hess K, Weiser M, Groome P . Personalizing prognosis in colorectal cancer: A systematic review of the quality and nature of clinical prognostic tools for survival outcomes. J Surg Oncol. 2017; 116(8):969-982. PMC: 5760443. DOI: 10.1002/jso.24774. View

Suriyaamporn P, Opanasopit P, Rangsimawong W, Ngawhirunpat T . Optimal Design of Novel Microemulsions-Based Two-Layered Dissolving Microneedles for Delivering Fluconazole in Treatment of Fungal Eye Infection. Pharmaceutics. 2022; 14(3). PMC: 8951261. DOI: 10.3390/pharmaceutics14030472. View

Martinez-Bosch N, Guerrero P, Moreno M, Jose A, Iglesias M, Munne-Collado J . The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. Oncotarget. 2016; 7(30):48265-48279. PMC: 5217016. DOI: 10.18632/oncotarget.10199. View

10.

Ning S, Lee S, Wei M, Peng C, Lin S, Tsai M . Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133 Antibody-Conjugated SN-38 Nanoparticles. ACS Appl Mater Interfaces. 2016; 8(28):17793-804. DOI: 10.1021/acsami.6b04403. View

11.

Charasson V, Haaz M, Robert J . Determination of drug interactions occurring with the metabolic pathways of irinotecan. Drug Metab Dispos. 2002; 30(6):731-3. DOI: 10.1124/dmd.30.6.731. View

12.

Giuliano S, Cormerais Y, Dufies M, Grepin R, Colosetti P, Belaid A . Resistance to sunitinib in renal clear cell carcinoma results from sequestration in lysosomes and inhibition of the autophagic flux. Autophagy. 2015; 11(10):1891-904. PMC: 4824581. DOI: 10.1080/15548627.2015.1085742. View

13.

Schraa S, Frerichs K, Agterof M, Hunting J, Los M, de Jong P . Relative dose intensity as a proxy measure of quality and prognosis in adjuvant chemotherapy for breast cancer in daily clinical practice. Eur J Cancer. 2017; 79:152-157. DOI: 10.1016/j.ejca.2017.04.001. View

14.

Serova M, Tijeras-Raballand A, Dos Santos C, Martinet M, Neuzillet C, Lopez A . Everolimus affects vasculogenic mimicry in renal carcinoma resistant to sunitinib. Oncotarget. 2016; 7(25):38467-86. PMC: 5122404. DOI: 10.18632/oncotarget.9542. View

15.

Joseph J, Sangeetha D, Gomathi T . Sunitinib loaded chitosan nanoparticles formulation and its evaluation. Int J Biol Macromol. 2015; 82:952-8. DOI: 10.1016/j.ijbiomac.2015.10.079. View

16.

Wragg J, Heath V, Bicknell R . Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors. Cancer Res. 2016; 77(4):1008-1020. PMC: 5321582. DOI: 10.1158/0008-5472.CAN-16-1982. View

17.

Patnaik A, Swanson K, Csizmadia E, Solanki A, Landon-Brace N, Gehring M . Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity. Cancer Discov. 2017; 7(7):750-765. PMC: 5501767. DOI: 10.1158/2159-8290.CD-16-0778. View

18.

Peng C, Shieh M, Tsai M, Chang C, Lai P . Self-assembled star-shaped chlorin-core poly(epsilon-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies. Biomaterials. 2008; 29(26):3599-608. DOI: 10.1016/j.biomaterials.2008.05.018. View

19.

Jaxel C, Kohn K, Wani M, Wall M, Pommier Y . Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res. 1989; 49(6):1465-9. View

20.

Majumder S, Piguet A, Dufour J, Chatterjee S . Study of the cellular mechanism of Sunitinib mediated inactivation of activated hepatic stellate cells and its implications in angiogenesis. Eur J Pharmacol. 2013; 705(1-3):86-95. DOI: 10.1016/j.ejphar.2013.02.026. View