A photothermal/chemotherapy injectable paclitaxel gel with irradiation stability_Journal of Biomedical Engineering

Authors：

OUYANG Yaowen ¹ , ZHANG Kui ¹ , ZHOU Liangqin ¹ , CHEN Yuanwei ¹ ,  LUO Xianglin ^1,2

1. College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, P.R.China;
2. State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, P.R.China;

Corresponding author：

LUO Xianglin, Email: Luoxl_scu@126.com

Keywords：

injectable drug gel; photothermal-chemotherapy combination; photothermal cycle stability; tumor therapy

DOI：

10.7507/1001-5515.202011087

Video：

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The aim of this study is to construct an injectable gel with stable phototherapy and chemotherapy. Res-PTX@IR780 gel with phototherapy and chemotherapy property was prepared by introduction of photosensitizer IR780 and antioxidant resveratrol (Res) into the polyethylene glycol (PEG) solution of paclitaxel (PTX). The results showed that PTX, PTX@IR780 and Res-PTX@IR780 could form gels and the gels were injectable. ATR-FTIR results indicated not only components of the gels but also the formation of hydrogen bonding during the gelation. The results of UV showed instability of IR780 solution and stability improvement of Res-IR780 solution under infrared radiation (IR) irradiation. Photothermal tests showed that Res-PTX@IR780 displayed better photothermal conversion and photothermal stability under multiple irradiations than PTX@IR780. The results of in vivo exploration in mice showed that the skin site injected with Res-PTX@IR780 gel heated up from 35 ℃ to 64 ℃, and the temperature difference was up to 30 ℃. Res-PTX@IR780 gel is very promising as a combination agent of photothermal therapy and chemotherapy for the in situ treatment of tumors due to good photothermal conversion and photothermal stability under multiple irradiations.

Citation： OUYANG Yaowen, ZHANG Kui, ZHOU Liangqin, CHEN Yuanwei, LUO Xianglin. A photothermal/chemotherapy injectable paclitaxel gel with irradiation stability. Journal of Biomedical Engineering, 2021, 38(5): 979-985. doi: 10.7507/1001-5515.202011087 Copy

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2.	Thambi T, Li Y, Lee D S. Injectable hydrogels for sustained release of therapeutic agents. J Control Release, 2017, 267: 57-66.
3.	Dimatteo R, Darling N J, Segura T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliver Rev, 2018, 127: 167-184.
4.	Kingston D G I. Taxol: The chemistry and structure-activity relationships of a novel anticancer agent. Trends Biotechnol, 1994, 12(6): 222-227.
5.	Wang F, Porter M, Konstantopoulos A, et al. Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy. J Control Release, 2017, 267: 100-118.
6.	Mao L, Wang H, Tan M, et al. Conjugation of two complementary anti-cancer drugs confers molecular hydrogels as a co-delivery system. Chem Commun, 2012, 48(3): 395-397.
7.	Song Q, Zhang R, Lei L, et al. Self-assembly of succinated paclitaxel into supramolecular hydrogel for local cancer chemotherapy. J Biomed Nanotechnol, 2018, 14(8): 1471-1476.
8.	Wang H, Lv L, Xu G, et al. Molecular hydrogelators consist of Taxol and short peptides/amino acids. J Mater Chem, 2012, 22(33): 16933-16938.
9.	Wang H, Wei J, Yang C, et al. The inhibition of tumor growth and metastasis by self-assembled nanofibers of taxol. Biomaterials, 2012, 33(24): 5848-5853.
10.	Zhang K, Zhou L, Chen F, et al. Injectable gel self-assembled by paclitaxel itself for in situ inhibition of tumor growth. J Control Release, 2019, 315: 197-205.
11.	Liu C, Ruan C, Shi R, et al. A near infrared-modulated thermosensitive hydrogel for stabilization of indocyanine green and combinatorial anticancer phototherapy. Biomater Sci-UK, 2019, 7(4): 1705-1715.
12.	Pais-Silva C, De Melo-Diogo D, Correia I J. IR780-loaded tpgs-tos micelles for breast cancer photodynamic therapy. Eur J Pharm Biopharm, 2017, 113: 108-117.
13.	Alves C G, Lima-Sousa R, De Melo-Diogo D, et al. IR780 based nanomaterials for cancer imaging and photothermal, photodynamic and combinatorial therapies. Int J Pharmaceut, 2018, 542(1-2): 164-175.
14.	Li Y, Zhou Q, Deng Z, et al. IR-780 dye as a sonosensitizer for sonodynamic therapy of breast tumor. Sci Rep-UK, 2016, 6(1): 25968.
15.	Gorka A P, Schnermann M J. Harnessing cyanine photooxidation: From slowing photobleaching to near-ir uncaging. Curr Opin Chem Biol, 2016, 33: 117-125.
16.	Widengren J C A, Eggeling C, et al. Strategies to improve photostabilities in ultrasensitive fluorescence spectroscopy. J Phys Chem A, 2007: 429-440.
17.	Vogelsang J, Kasper R, Steinhauer C, et al. A reducing and oxidizing system minimizes photobleaching and blinking of fluorescent dyes. Angew Chem Int Edit, 2008, 47(29): 5465-5469.
18.	Glembockyte V, Lincoln R, Cosa G. Cy3 photoprotection mediated by ni²⁺ for extended single-molecule imaging: Old tricks for new techniques. J Am Chem Soc, 2015, 137(3): 1116-1122.
19.	King R E, Bomser J A, Min D B. Bioactivity of resveratrol. Compr Rev Food Sci F, 2006, 5(3): 65-70.
20.	Fiod Riccio B V, Fonseca-Santos B, Colerato Ferrari P, et al. Characteristics, biological properties and analytical methods of trans-resveratrol: A review. Crit Rev Anal Chem, 2020, 50(4): 339-358.
21.	Miele D, Catenacci L, Sorrenti M, et al. Chitosan oleate coated poly lactic-glycolic acid (PLGA) nanoparticles versus chitosan oleate self-assembled polymeric micelles, loaded with resveratrol. Mar Drugs, 2019, 17(9): 515.
22.	Tang B, Fang G, Gao Y, et al. Liprosomes loading paclitaxel for brain-targeting delivery by intravenous administration: In vitro characterization and in vivo evaluation. Int J Pharmaceut, 2014, 475(1-2): 416-427.
23.	Nikfarjam M, Muralidharan V, Christophi C. Mechanisms of focal heat destruction of liver tumors. J Surg Res, 2005, 127(2): 208-223.
24.	Nani R R, Kelley J A, Ivanic J, et al. Reactive species involved in the regioselective photooxidation of heptamethine cyanines. Chem Sci, 2015, 6(11): 6556-6563.
25.	Ko J H, Sethi G, Um J Y, et al. The role of resveratrol in cancer therapy. Int J Mol Med, 2017, 18(12): 2589.

1. Sepantafar M, Maheronnaghsh R, Mohammadi H, et al. Engineered hydrogels in cancer therapy and diagnosis. Trends Biotechnol, 2017, 35(11): 1074-1087.
2. Thambi T, Li Y, Lee D S. Injectable hydrogels for sustained release of therapeutic agents. J Control Release, 2017, 267: 57-66.
3. Dimatteo R, Darling N J, Segura T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliver Rev, 2018, 127: 167-184.
4. Kingston D G I. Taxol: The chemistry and structure-activity relationships of a novel anticancer agent. Trends Biotechnol, 1994, 12(6): 222-227.
5. Wang F, Porter M, Konstantopoulos A, et al. Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy. J Control Release, 2017, 267: 100-118.
6. Mao L, Wang H, Tan M, et al. Conjugation of two complementary anti-cancer drugs confers molecular hydrogels as a co-delivery system. Chem Commun, 2012, 48(3): 395-397.
7. Song Q, Zhang R, Lei L, et al. Self-assembly of succinated paclitaxel into supramolecular hydrogel for local cancer chemotherapy. J Biomed Nanotechnol, 2018, 14(8): 1471-1476.
8. Wang H, Lv L, Xu G, et al. Molecular hydrogelators consist of Taxol and short peptides/amino acids. J Mater Chem, 2012, 22(33): 16933-16938.
9. Wang H, Wei J, Yang C, et al. The inhibition of tumor growth and metastasis by self-assembled nanofibers of taxol. Biomaterials, 2012, 33(24): 5848-5853.
10. Zhang K, Zhou L, Chen F, et al. Injectable gel self-assembled by paclitaxel itself for in situ inhibition of tumor growth. J Control Release, 2019, 315: 197-205.
11. Liu C, Ruan C, Shi R, et al. A near infrared-modulated thermosensitive hydrogel for stabilization of indocyanine green and combinatorial anticancer phototherapy. Biomater Sci-UK, 2019, 7(4): 1705-1715.
12. Pais-Silva C, De Melo-Diogo D, Correia I J. IR780-loaded tpgs-tos micelles for breast cancer photodynamic therapy. Eur J Pharm Biopharm, 2017, 113: 108-117.
13. Alves C G, Lima-Sousa R, De Melo-Diogo D, et al. IR780 based nanomaterials for cancer imaging and photothermal, photodynamic and combinatorial therapies. Int J Pharmaceut, 2018, 542(1-2): 164-175.
14. Li Y, Zhou Q, Deng Z, et al. IR-780 dye as a sonosensitizer for sonodynamic therapy of breast tumor. Sci Rep-UK, 2016, 6(1): 25968.
15. Gorka A P, Schnermann M J. Harnessing cyanine photooxidation: From slowing photobleaching to near-ir uncaging. Curr Opin Chem Biol, 2016, 33: 117-125.
16. Widengren J C A, Eggeling C, et al. Strategies to improve photostabilities in ultrasensitive fluorescence spectroscopy. J Phys Chem A, 2007: 429-440.
17. Vogelsang J, Kasper R, Steinhauer C, et al. A reducing and oxidizing system minimizes photobleaching and blinking of fluorescent dyes. Angew Chem Int Edit, 2008, 47(29): 5465-5469.
18. Glembockyte V, Lincoln R, Cosa G. Cy3 photoprotection mediated by ni²⁺ for extended single-molecule imaging: Old tricks for new techniques. J Am Chem Soc, 2015, 137(3): 1116-1122.
19. King R E, Bomser J A, Min D B. Bioactivity of resveratrol. Compr Rev Food Sci F, 2006, 5(3): 65-70.
20. Fiod Riccio B V, Fonseca-Santos B, Colerato Ferrari P, et al. Characteristics, biological properties and analytical methods of trans-resveratrol: A review. Crit Rev Anal Chem, 2020, 50(4): 339-358.
21. Miele D, Catenacci L, Sorrenti M, et al. Chitosan oleate coated poly lactic-glycolic acid (PLGA) nanoparticles versus chitosan oleate self-assembled polymeric micelles, loaded with resveratrol. Mar Drugs, 2019, 17(9): 515.
22. Tang B, Fang G, Gao Y, et al. Liprosomes loading paclitaxel for brain-targeting delivery by intravenous administration: In vitro characterization and in vivo evaluation. Int J Pharmaceut, 2014, 475(1-2): 416-427.
23. Nikfarjam M, Muralidharan V, Christophi C. Mechanisms of focal heat destruction of liver tumors. J Surg Res, 2005, 127(2): 208-223.
24. Nani R R, Kelley J A, Ivanic J, et al. Reactive species involved in the regioselective photooxidation of heptamethine cyanines. Chem Sci, 2015, 6(11): 6556-6563.
25. Ko J H, Sethi G, Um J Y, et al. The role of resveratrol in cancer therapy. Int J Mol Med, 2017, 18(12): 2589.

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