EFFECTIVE DRUG DELIVERY SYSTEMS IN LOCALIZED BREAST CANCER THERAPIES: INJECTABLE HYDROGELS

Öz

Objective: Breast cancer is the most common cancer in women worldwide and is a critical health problem that requires continuous research for early detection and development of effective treatment strategies. There is a need to develop innovative treatment modalities to overcome the limitations of conventional chemotherapy such as non-specific targeting, systemic toxicity, drug resistance and limited drug penetration. As drug delivery systems, injectable hydrogels have come to the forefront in local cancer treatments due to their biodegradable, biocompatible, design-adjustable physicochemical properties as well as their ability to provide highly efficient loading and release of the active substance. Injectable biodegradable hydrogels are critical in preventing cancer recurrence and metastasis, especially in the post surgical treatment process. In this review, we aimed to evaluate the structures, types, cancer treatment applications and anticancer therapeutic efficacy of injectable hydrogels. Result and Discussion: In this review, the structures of injectable hydrogels as pharmaceutical drug delivery systems, their applications in breast cancer treatments and their anticancer therapeutic efficacy for breast cancer were discussed.

Anahtar Kelimeler

• Breast cancer
• drug delivery system
• injectable hydrogel
• local therapy

LOKALİZE MEME KANSERİ TEDAVİLERİNDE EFEKTİF İLAÇ TAŞIYICI SİSTEMLER: ENJEKTABL HİDROJELLER

Öz

Amaç: Meme kanseri dünya genelinde kadınlarda en sık gözlenen kanser türü olup, erken teşhis ve etkili tedavi stratejilerinin geliştirilmesi için sürekli araştırmaların yapılmasını gerektiren kritik bir sağlık sorunudur. Geleneksel kemoterapi uygulamalarındaki spesifik olmayan hedefleme, sistemik toksisite, ilaç direnci, kısıtlı ilaç penetrasyonu gibi sınırlamaların aşılmasında yenilikçi tedavi yöntemlerinin geliştirilmesine ihtiyaç duyulmaktadır. İlaç taşıyıcı sistemler olarak enjektabl hidrojeller biyoparçalanır, biyouyumlu, tasarıma yönelik ayarlanabilir fizikokimyasal özelliklerinin yanı sıra etkin maddenin yüksek verimlilikte yüklenmesini ve salımını sağlayabilmesi dolayısıyla lokal kanser tedavilerinde ön plana çıkmaktadır. Enjektabl biyoparçalanır hidrojeller özellikle cerrahi sonrası tedavi sürecinde tümör nüksünü ve metastazını önlemede kritik öneme sahiptir. Bu derlemede enjektabl hidrojellerin yapıları, türleri, kanser tedavilerine ilişkin uygulamaları ve antikanser tedavi etkinliklerinin değerlendirilmesi amaçlanmıştır. Sonuç ve Tartışma: Bu derlemede farmasötik ilaç taşıyıcı sistemler olarak enjektabl hidrojel yapıları, meme kanseri tedavilerine ilişkin uygulamaları ve meme kanserine yönelik antikanser tedavi etkinlikleri ele alınmıştır.

Anahtar Kelimeler

• Enjektabl hidrojel
• ilaç taşıyıcı sistem
• lokal tedavi
• meme kanseri

Kaynakça

1. 1. Momenimovahed, Z., Salehiniya, H. (2019). Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer: Targets and Therapy, 11, 151-164. [CrossRef]
2. 2. Shien, T., Iwata, H. (2020). Adjuvant and neoadjuvant therapy for breast cancer. Japanese Journal of Clinical Oncology, 50(3), 225-229. [CrossRef]
3. 3. Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D.M., Pineros, M., Znaor, A., Bray, F. (2021). Cancer statistics for the year 2020: An overview. International Journal of Cancer, 149(4), 778-789. [CrossRef]
4. 4. Fahad Ullah, M. (2019). Breast cancer: Current perspectives on the disease status. Breast Cancer Metastasis and Drug Resistance: Challenges and Progress, Advances in Experimental Medicine, Springer, Cham, 1152, 51-64. [CrossRef]
5. 5. Sulman, E.P., Ismaila, N., Armstrong, T.S., Tsien, C., Batchelor, T.T., Cloughesy, T., Galanis, E., Gilbert, M., Gondi, V., Lovely, M., Mehta, M., Mumber, M.P., Sloan, A., Chang, S.M. (2017). Radiation therapy for glioblastoma: American society of clinical oncology clinical practice guideline endorsement of the american society for radiation oncology guideline. Journal of Clinical Oncology, 35(3), 361-369. [CrossRef]
6. 6. Springfeld, C., Jäger, D., Büchler, M.W., Strobel, O., Hackert, T., Palmer, D.H., Neoptolemos, J.P. (2019). Chemotherapy for pancreatic cancer. La Presse Medicale, 48(3), 159-174. [CrossRef]
7. 7. Carr, C., Ng, J., Wigmore, T. (2008). The side effects of chemotherapeutic agents. Current Anaesthesia & Critical Care, 19(2), 70-79. [CrossRef]
8. 8. Zamboni, W.C. (2005). Liposomal, nanoparticle, and conjugated formulations of anticancer agents. Clinical Cancer Research, 11(23), 8230-8234. [CrossRef]

9. 9. Sepantafar, M., Maheronnaghsh, R., Mohammadi, H., Radmanesh, F., Hasani-Sadrabadi, M.M., Ebrahimi, M., Baharvand, H. (2017). Engineered hydrogels in cancer therapy and diagnosis. Trends in Biotechnology, 35(11), 1074-1087. [CrossRef]
10. 10. Nguyen, K., Dang, P.N., Alsberg, E. (2013). Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells. Acta Biomaterialia, 9(1), 4487-4495. [CrossRef]
11. 11. Wang, W., Narain, R., Zeng, H. (2020). Hydrogels. In Polymer Science and Nanotechnology, Elsevier, Canada, p.203-244. [CrossRef]
12. 12. Wu, W., Chen, H., Shan, F., Zhou, J., Sun, X., Zhang, L., Gong, T. (2014). A novel doxorubicin-loaded in situ forming gel based high concentration of phospholipid for intratumoral drug delivery. Molecular Pharmaceutics, 11(10), 3378-3385. [CrossRef]
13. 13. Basaran, B., Bozkir, A. (2012). Thermosensitive and pH induced in situ ophthalmic gelling system for ciprofloxacin hydrochloride: Hydroxypropyl-beta-cyclodextrin complex. Acta Poloniae Pharmaceutica, 69(6), 1137-1147.
14. 14. Oz, U.C., Toptas, M., Kucukturkmen, B., Devrim, B., Saka, O.M., Deveci, M.S., Bilgili, H., Unsal, E., Bozkir, A. (2020). Guided bone regeneration by the development of alendronate sodium loaded in-situ gel and membrane formulations. European Journal of Pharmaceutical Sciences, 155, 105561. [CrossRef]
15. 15. Kucukturkmen, B., Oz, U.C., Bozkir, A. (2017). In situ hydrogel formulation for ıntra-articular application of diclofenac sodium-loaded polymeric nanoparticles. Turkish Journal of Pharmaceutical Sciences, 14(1), 56-64. [CrossRef]
16. 16. Ozbilgin, N.D., Saka, O.M., Bozkir, A. (2014). Preparation and in vitro/in vivo evaluation of mucosal adjuvant in situ forming gels with diphtheria toxoid. Drug Delivery, 21(2), 140-147. [CrossRef]
17. 17. Nguyen, M.K., Lee, D.S. (2010). Injectable biodegradable hydrogels. Macromolecular Bioscience, 10(6), 563-579. [CrossRef]
18. 18. Xie, Z., Shen, J., Sun, H., Li, J., Wang, X. (2021). Polymer-based hydrogels with local drug release for cancer immunotherapy. Biomedicine & Pharmacotherapy, 137, 111333. [CrossRef]
19. 19. Liu, H., Shi, X., Wu, D., Kahsay Khshen, F., Deng, L., Dong, A., Wang, W., Zhang, J. (2019). Injectable, biodegradable, thermosensitive nanoparticles-aggregated hydrogel with tumor-specific targeting, penetration, and release for efficient postsurgical prevention of tumor recurrence. ACS Applied Materials & Interfaces, 11(22), 19700-19711. [CrossRef]
20. 20. Cirillo, G., Spizzirri, U.G., Curcio, M., Nicoletta, F.P., Iemma, F. (2019). Injectable hydrogels for cancer therapy over the last decade. Pharmaceutics, 11(9), 486. [CrossRef]
21. 21. Ahmad, Z., Salman, S., Khan, S.A., Amin, A., Rahman, Z.U., Al-Ghamdi, Y.O., Akhtar, K., Bakhsh, E.M., Khan, S.B. (2022). Versatility of hydrogels: From synthetic strategies, classification, and properties to biomedical applications. Gels, 8(3), 167. [CrossRef]
22. 22. Catoira, M.C., Fusaro, L., Di Francesco, D., Ramella, M., Boccafoschi, F. (2019). Overview of natural hydrogels for regenerative medicine applications. Journal of Materials Science: Materials in Medicine, 30(10), 115. [CrossRef]
23. 23. Radhakrishnan, J., Subramanian, A., Krishnan, U.M., Sethuraman, S. (2017). Injectable and 3D bioprinted polysaccharide hydrogels: From cartilage to osteochondral tissue engineering. Biomacromolecules, 18(1), 1-26. [CrossRef]
24. 24. Luo, F.Q., Xu, W., Zhang, J.Y., Liu, R., Huang, Y.C., Xiao, C., Du, J.Z. (2022). An injectable nanocomposite hydrogel improves tumor penetration and cancer treatment efficacy. Acta Biomaterialia, 147, 235-244. [CrossRef]
25. 25. Cacicedo, M.L., Islan, G.A., Leon, I.E., Alvarez, V.A., Chourpa, I., Allard-Vannier, E., Garcia-Aranda, N., Diaz-Riascos, Z.V., Fernandez, Y., Schwartz, S., Jr., Abasolo, I., Castro, G.R. (2018). Bacterial cellulose hydrogel loaded with lipid nanoparticles for localized cancer treatment. Colloids Surf B Biointerfaces, 170, 596-608. [CrossRef]
26. 26. Nieto, C., Vega, M.A., Rodriguez, V., Perez-Esteban, P., Martin Del Valle, E.M. (2022). Biodegradable gellan gum hydrogels loaded with paclitaxel for HER2+ breast cancer local therapy. Carbohydrate Polymers, 294, 119732. [CrossRef]
27. 27. Leng, Q., Li, Y., Zhou, P., Xiong, K., Lu, Y., Cui, Y., Wang, B., Wu, Z., Zhao, L., Fu, S. (2021). Injectable hydrogel loaded with paclitaxel and epirubicin to prevent postoperative recurrence and metastasis of breast cancer. Materials Science and Engineering: C, 129, 112390. [CrossRef]
28. 28. Chao, Y., Liang, C., Tao, H., Du, Y., Wu, D., Dong, Z., Jin, Q., Chen, G., Xu, J., Xiao, Z., Chen, Q., Wang, C., Chen, J., Liu, Z. (2020). Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses. Science Advances, 6(10), eaaz4204. [CrossRef]
29. 29. Abdellatif, A.A.H., Mohammed, A.M., Saleem, I., Alsharidah, M., Al Rugaie, O., Ahmed, F., Osman, S.K. (2022). Smart injectable chitosan hydrogels loaded with 5-fluorouracil for the treatment of breast cancer. Pharmaceutics, 14(3), 661. [CrossRef]
30. 30. Davoodi-Monfared, P., Akbari-Birgani, S., Mohammadi, S., Kazemi, F., Nikfarjam, N., Nikbakht, M., Mousavi, S.A. (2021). Synthesis, characterization, and in vitro evaluation of the starch-based alpha-amylase responsive hydrogels. Journal of Cellular Physiology, 236(5), 4066-4075. [CrossRef]
31. 31. Safarzadeh Kozani, P., Safarzadeh Kozani, P., Hamidi, M., Valentine Okoro, O., Eskandani, M., Jaymand, M. (2022). Polysaccharide-based hydrogels: Properties, advantages, challenges, and optimization methods for applications in regenerative medicine. International Journal of Polymeric Materials and Polymeric Biomaterials, 71(17), 1319-1333. [CrossRef]
32. 32. Madduma‐Bandarage, U.S., Madihally, S.V. (2021). Synthetic hydrogels: Synthesis, novel trends, and applications. Journal of Applied Polymer Science, 138(19), 50376. [CrossRef]
33. 33. Liu, F., Wang, X. (2020). Synthetic polymers for organ 3D printing. Polymers, 12(8), 1765. [CrossRef]
34. 34. Dong, X., Wei, C., Liang, J., Liu, T., Kong, D., Lv, F. (2017). Thermosensitive hydrogel loaded with chitosan-carbon nanotubes for near infrared light triggered drug delivery. Colloids and Surfaces B: Biointerfaces, 154, 253-262. [CrossRef]
35. 35. Chen, M., Tan, Y., Hu, J., Jiang, Y., Wang, Z., Liu, Z., Chen, Q. (2021). Injectable immunotherapeutic thermogel for enhanced immunotherapy post tumor radiofrequency ablation. Small, 17(52), 2104773. [CrossRef]
36. 36. Li, S., Zhou, D., Pei, M., Zhou, Y., Xu, W., Xiao, P. (2020). Fast gelling and non-swellable photopolymerized poly (vinyl alcohol) hydrogels with high strength. European Polymer Journal, 134, 109854. [CrossRef]
37. 37. Ji, H., Song, X., Cheng, H., Luo, L., Huang, J., He, C., Yin, J., Zhao, W., Qiu, L., Zhao, C. (2020). Biocompatible in situ polymerization of multipurpose polyacrylamide-based hydrogels on skin via silver ion catalyzation. ACS Applied Materials & Interfaces, 12(28), 31079-31089. [CrossRef]
38. 38. Cocarta, A.I., Hobzova, R., Trchova, M., Svojgr, K., Kodetova, M., Pochop, P., Uhlik, J., Sirc, J. (2021). 2‐Hydroxyethyl methacrylate hydrogels for local drug delivery: Study of topotecan and vincristine sorption/desorption kinetics and polymer‐drug interaction by ATR‐FTIR spectroscopy. Macromolecular Chemistry and Physics, 222(13), 2100086. [CrossRef]
39. 39. Yu, J., Qiu, H., Yin, S., Wang, H., Li, Y. (2021). Polymeric drug delivery system based on pluronics for cancer treatment. Molecules, 26(12), 3610. [CrossRef]
40. 40. Lei, N., Gong, C., Qian, Z., Luo, F., Wang, C., Wang, H., Wei, Y. (2012). Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model. Nanoscale, 4(18), 5686-5693. [CrossRef]
41. 41. Norouzi, M., Firouzi, J., Sodeifi, N., Ebrahimi, M., Miller, D.W. (2021). Salinomycin-loaded injectable thermosensitive hydrogels for glioblastoma therapy. International Journal of Pharmaceutics, 598, 120316. [CrossRef]
42. 42. Wang, Y., Zhang, W., Gong, C., Liu, B., Li, Y., Wang, L., Su, Z., Wei, G. (2020). Recent advances in the fabrication, functionalization, and bioapplications of peptide hydrogels. Soft Matter, 16(44), 10029-10045. [CrossRef]
43. 43. Mathew, A.P., Uthaman, S., Cho, K-H., Cho, C.-S., Park, I.K. (2018). Injectable hydrogels for delivering biotherapeutic molecules. International Journal of Biological Macromolecules, 110, 17-29. [CrossRef]
44. 44. Li, Y., Liu, Y., Guo, Q. (2021). Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2. Arthritis Research & Therapy, 23(1), 1-11. [CrossRef]
45. 45. Zhao, N., Suzuki, A., Zhang, X., Shi, P., Abune, L., Coyne, J., Jia, H., Xiong, N., Zhang, G., Wang, Y. (2019). Dual aptamer-functionalized in situ injectable fibrin hydrogel for promotion of angiogenesis via codelivery of vascular endothelial growth factor and platelet-derived growth factor-BB. ACS Applied Materials & Interfaces, 11(20), 18123-18132. [CrossRef]
46. 46. Lu, Y., Zhao, M., Peng, Y., He, S., Zhu, X., Hu, C., Xia, G., Zuo, T., Zhang, X., Yun, Y. (2022). A physicochemical double-cross-linked gelatin hydrogel with enhanced antibacterial and anti-inflammatory capabilities for improving wound healing. Journal of Nanobiotechnology, 20(1), 1-26. [CrossRef]
47. 47. Lin, K., Zhang, D., Macedo, M.H., Cui, W., Sarmento, B., Shen, G. (2019). Advanced collagen‐based biomaterials for regenerative biomedicine. Advanced Functional Materials, 29(3), 1804943. [CrossRef]
48. 48. Dufour, A., Mallein-Gerin, F., Perrier-Groult, E. (2021). Direct perfusion improves redifferentiation of human chondrocytes in fibrin hydrogel with the deposition of cartilage pericellular matrix. Applied Sciences, 11(19), 8923. [CrossRef]
49. 49. Yu, S., Wei, S., Liu, L., Qi, D., Wang, J., Chen, G., He, W., He, C., Chen, X., Gu, Z. (2019). Enhanced local cancer therapy using a CA4P and CDDP co-loaded polypeptide gel depot. Biomaterials Science, 7(3), 860-866. [CrossRef]
50. 50. Qi, Y., Min, H., Mujeeb, A., Zhang, Y., Han, X., Zhao, X., Anderson, G.J., Zhao, Y., Nie, G. (2018). Injectable hexapeptide hydrogel for localized chemotherapy prevents breast cancer recurrence. ACS Applied Materials & Interfaces, 10(8), 6972-6981. [CrossRef]
51. 51. Hou, X.L., Dai, X., Yang, J., Zhang, B., Zhao, D.H., Li, C.Q., Yin, Z.Y., Liu, B. (2020). Injectable polypeptide-engineered hydrogel depot for amplifying the anti-tumor immune effect induced by chemo-photothermal therapy. Journal of Materials Chemistry B, 8(37), 8623-8633. [CrossRef]
52. 52. Franks, S.J., Firipis, K., Ferreira, R., Hannan, K.M., Williams, R.J., Hannan, R.D., Nisbet, D.R. (2020). Harnessing the self-assembly of peptides for the targeted delivery of anti-cancer agents. Materials Horizons, 7(8), 1996-2010. [CrossRef]
53. 53. Leach, D.G., Dharmaraj, N., Lopez-Silva, T.L., Venzor, J.R., Pogostin, B.H., Sikora, A.G., Hartgerink, J.D., Young, S. (2021). Biomaterial-facilitated immunotherapy for established oral cancers. ACS Biomaterials Science & Engineering, 7(2), 415-421. [CrossRef]
54. 54. Um, S.H., Lee, J.B., Park, N., Kwon, S.Y., Umbach, C.C., Luo, D. (2006). Enzyme-catalysed assembly of DNA hydrogel. Nature Materials, 5(10), 797-801. [CrossRef]
55. 55. Gačanin, J., Synatschke, C.V., Weil, T. (2020). Biomedical applications of DNA‐based hydrogels. Advanced Functional Materials, 30(4), 1906253. [CrossRef]
56. 56. Ding, L., Li, J., Wu, C., Yan, F., Li, X., Zhang, S. (2020). A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer. Journal of Materials Chemistry B, 8(16), 3527-3533. [CrossRef]
57. 57. Zhang, J., Guo, Y., Pan, G., Wang, P., Li, Y., Zhu, X., Zhang, C. (2020). Injectable drug-conjugated DNA hydrogel for local chemotherapy to prevent tumor recurrence. ACS Applied Materials & Interfaces, 12(19), 21441-21449. [CrossRef]
58. 58. Mohammadi, M., Karimi, M., Malaekeh-Nikouei, B., Torkashvand, M., Alibolandi, M. (2022). Hybrid in situ-forming injectable hydrogels for local cancer therapy. International Journal of Pharmaceutics, 616, 121534. [CrossRef]
59. 59. Cimen, Z., Babadag, S., Odabas, S., Altuntas, S., Demirel, G., Demirel, G.B. (2021). Injectable and self-healable pH-responsive gelatin–PEG/laponite hybrid hydrogels as long-acting implants for local cancer treatment. ACS Applied Polymer Materials, 3(7), 3504-3518. [CrossRef]
60. 60. Cacicedo, M.L., Islan, G.A., León, I.E., Alvarez, V.A., Chourpa, I., Allard-Vannier, E., García-Aranda, N., Díaz-Riascos, Z., Fernández, Y., Schwartz Jr, S. (2018). Bacterial cellulose hydrogel loaded with lipid nanoparticles for localized cancer treatment. Colloids and Surfaces B: Biointerfaces, 170, 596-608. [CrossRef]
61. 61. Wang, C.Y., Sun, M., Fan, Z., Du, J.Z. (2022). Intestine enzyme-responsive polysaccharide-based hydrogel to open epithelial tight junctions for oral delivery of imatinib against colon cancer. Chinese Journal of Polymer Science, 40(10), 1154-1164. [CrossRef]
62. 62. Koetting, M.C., Peters, J.T., Steichen, S.D., Peppas, N.A. (2015). Stimulus-responsive hydrogels: Theory, modern advances, and applications. Materials Science and Engineering: R: Reports, 93, 1-49. [CrossRef]
63. 63. Xu, J., Yin, Z., Zhang, L., Dong, Q., Cai, X., Li, S., Chen, Q., Keoingthong, P., Li, Z., Chen, L. (2022). Hydrogen-bonding-induced H-aggregation of charge-transfer complexes for ultra-efficient second near-infrared region photothermal conversion. CCS Chemistry, 4(7), 2333-2343. [CrossRef]
64. 64. Chakraborty, D.D., Nath, L., Chakraborty, P. (2018). Recent progress in smart polymers: Behavior, mechanistic understanding and application. Polymer-Plastics Technology and Engineering, 57(10), 945-957. [CrossRef]
65. 65. Klouda, L. (2015). Thermoresponsive hydrogels in biomedical applications: A seven-year update. European Journal of Pharmaceutics and Biopharmaceutics, 97, 338-349. [CrossRef]
66. 66. Zhang, L., Guan, X., Xiao, X., Chai, Y., Chen, Z., Zhou, G., Fan, Y. (2022). Near-infrared triggered injectable ferrimagnetic chitosan thermosensitive hydrogel for photo hyperthermia and precisely controlled drug release in tumor ablation. European Polymer Journal, 162, 110879. [CrossRef]
67. 67. Shokri, R., Fuentes-Chandía, M., Ai, J., Roudkenar, M.H., Mahboubian, A.R., Malekshahi, M.R., Ostad, S.N. (2022). A thermo-sensitive hydrogel composed of methylcellulose/hyaluronic acid/silk fibrin as a biomimetic extracellular matrix to simulate breast cancer malignancy. European Polymer Journal, 176, 111421. [CrossRef]
68. 68. Kotta, S., Aldawsari, H.M., Badr-Eldin, S.M., Nair, A.B., Kaleem, M., Dalhat, M.H. (2022). Thermosensitive hydrogels loaded with resveratrol nanoemulsion: Formulation optimization by central composite design and evaluation in MCF-7 human breast cancer cell lines. Gels, 8(7), 450. [CrossRef]
69. 69. Guo, J., Feng, Z., Liu, X., Wang, C., Huang, P., Zhang, J., Deng, L., Wang, W., Dong, A. (2020). An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy. Soft Matter, 16(24), 5750-5758. [CrossRef]
70. 70. Zhao, D., Hu, C., Fu, Q., Lv, H. (2021). Combined chemotherapy for triple negative breast cancer treatment by paclitaxel and niclosamide nanocrystals loaded thermosensitive hydrogel. European Journal of Pharmaceutical Sciences, 167, 105992. [CrossRef]
71. 71. Liu, Y., Ma, W., Zhou, P., Wen, Q., Wen, Q., Lu, Y., Zhao, L., Shi, H., Dai, J., Li, J. (2023). In situ administration of temperature-sensitive hydrogel composite loading paclitaxel microspheres and cisplatin for the treatment of melanoma. Biomedicine & Pharmacotherapy, 160, 114380. [CrossRef]
72. 72. Liu, Y., Luo, Y.N., Zhang, P., Yang, W.F., Zhang, C.-Y., Yin, Y.L. (2022). The preparation of novel P (OEGMA-co-MEO2MA) microgels-based thermosensitive hydrogel and its application in three-dimensional cell scaffold. Gels, 8(5), 313. [CrossRef]
73. 73. Dalwadi, C., Patel, G. (2018). Thermosensitive nanohydrogel of 5-fluorouracil for head and neck cancer: Preparation, characterization and cytotoxicity assay. International Journal of Nanomedicine, 13(sup1), 31-33. [CrossRef]
74. 74. Darge, H.F., Andrgie, A.T., Tsai, H.C., Lai, J.Y. (2019). Polysaccharide and polypeptide based injectable thermo-sensitive hydrogels for local biomedical applications. International Journal of Biological Macromolecules, 133, 545-563. [CrossRef]
75. 75. Darge, H.F., Hanurry, E.Y., Birhan, Y.S., Mekonnen, T.W., Andrgie, A.T., Chou, H.Y., Lai, J.Y., Tsai, H.C. (2021). Multifunctional drug-loaded micelles encapsulated in thermo-sensitive hydrogel for in vivo local cancer treatment: Synergistic effects of anti-vascular and immuno-chemotherapy. Chemical Engineering Journal, 406, 126879. [CrossRef]
76. 76. Fan, R., Sun, W., Zhang, T., Wang, R., Tian, Y., Zhang, H., Li, J., Zheng, A., Song, S. (2022). Paclitaxel-nanocrystals-loaded network thermosensitive hydrogel for localised postsurgical recurrent of breast cancer after surgical resection. Biomedicine & Pharmacotherapy, 150, 113017. [CrossRef]
77. 77. Persi, E., Duran-Frigola, M., Damaghi, M., Roush, W.R., Aloy, P., Cleveland, J.L., Gillies, R.J., Ruppin, E. (2018). Systems analysis of intracellular pH vulnerabilities for cancer therapy. Nature Communications, 9(1), 2997. [CrossRef]
78. 78. Hendi, A., Umair Hassan, M., Elsherif, M., Alqattan, B., Park, S., Yetisen, A.K., Butt, H. (2020). Healthcare applications of pH-Sensitive hydrogel-based devices: A review. International Journal of Nanomedicine, 3887-3901. [CrossRef]
79. 79. Kocak, G., Tuncer, C., Bütün, V. (2017). pH-Responsive polymers. Polymer Chemistry, 8(1), 144-176. [CrossRef]
80. 80. Rizwan, M., Yahya, R., Hassan, A., Yar, M., Azzahari, A.D., Selvanathan, V., Sonsudin, F., Abouloula, C.N. (2017). pH sensitive hydrogels in drug delivery: Brief history, properties, swelling, and release mechanism, material selection and applications. Polymers, 9(4), 137. [CrossRef]
81. 81. Liu, Y., Ran, Y., Ge, Y., Raza, F., Li, S., Zafar, H., Wu, Y., Paiva-Santos, A.C., Yu, C., Sun, M. (2022). pH-sensitive peptide hydrogels as a combination drug delivery system for cancer treatment. Pharmaceutics, 14(3), 652. [CrossRef]
82. 82. Sharma, P.K., Singh, Y. (2019). Glyoxylic hydrazone linkage-based PEG hydrogels for covalent entrapment and controlled delivery of doxorubicin. Biomacromolecules, 20(6), 2174-2184. [CrossRef]
83. 83. Li, L., Scheiger, J.M., Levkin, P.A. (2019). Design and applications of photoresponsive hydrogels. Advanced Materials, 31(26), 1807333. [CrossRef]
84. 84. Bustamante-Torres, M., Romero-Fierro, D., Arcentales-Vera, B., Palomino, K., Magaña, H., Bucio, E. (2021). Hydrogels classification according to the physical or chemical interactions and as stimuli-sensitive materials. Gels, 7(4), 182. [CrossRef]
85. 85. Ji, W., Wu, Q., Han, X., Zhang, W., Wei, W., Chen, L., Li, L., Huang, W. (2020). Photosensitive hydrogels: From structure, mechanisms, design to bioapplications. Science China Life Sciences, 63, 1813-1828. [CrossRef]
86. 86. Peng, K., Zheng, L., Zhou, T., Zhang, C., Li, H. (2022). Light manipulation for fabrication of hydrogels and their biological applications. Acta Biomaterialia, 137, 20-43. [CrossRef]
87. 87. Phan, L.M.T., Vo, T.A.T., Hoang, T.X., Cho, S. (2021). Graphene integrated hydrogels based biomaterials in photothermal biomedicine. Nanomaterials, 11(4), 906. [CrossRef]
88. 88. Mi, D., Li, J., Wang, R., Li, Y., Zou, L., Sun, C., Yan, S., Yang, H., Zhao, M., Shi, S. (2023). Postsurgical wound management and prevention of triple-negative breast cancer recurrence with a pryoptosis-inducing, photopolymerizable hydrogel. Journal of Controlled Release, 356, 205-218. [CrossRef]
89. 89. Kuppusamy, P., Li, H., Ilangovan, G., Cardounel, A.J., Zweier, J.L., Yamada, K., Krishna, M.C., Mitchell, J.B. (2002). Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels. Cancer Research, 62(1), 307-312.
90. 90. Quinn, J.F., Whittaker, M.R., Davis, T.P. (2017). Glutathione responsive polymers and their application in drug delivery systems. Polymer Chemistry, 8(1), 97-126. [CrossRef]
91. 91. Ye, H., Zhou, Y., Liu, X., Chen, Y., Duan, S., Zhu, R., Liu, Y., Yin, L. (2019). Recent advances on reactive oxygen species-responsive delivery and diagnosis system. Biomacromolecules, 20(7), 2441-2463. [CrossRef]
92. 92. Degirmenci, A., Ipek, H., Sanyal, R., Sanyal, A. (2022). Cyclodextrin-containing redox-responsive nanogels: Fabrication of a modular targeted drug delivery system. European Polymer Journal, 181, 111645. [CrossRef]
93. 93. Kasiński, A., Zielińska-Pisklak, M., Oledzka, E., Sobczak, M. (2020). Smart hydrogels-synthetic stimuli-responsive antitumor drug release systems. International Journal of Nanomedicine, 4541-4572. [CrossRef]
94. 94. Gerami, S.E., Pourmadadi, M., Fatoorehchi, H., Yazdian, F., Rashedi, H., Nigjeh, M.N. (2021). Preparation of pH-sensitive chitosan/polyvinylpyrrolidone/α-Fe2O3 nanocomposite for drug delivery application: Emphasis on ameliorating restrictions. International Journal of Biological Macromolecules, 173, 409-420. [CrossRef]
95. 95. Mahdi Eshaghi, M., Pourmadadi, M., Rahdar, A., Díez-Pascual, A.M. (2022). Novel carboxymethyl cellulose-based hydrogel with core-shell Fe3O4@ SiO2 nanoparticles for quercetin delivery. Materials, 15(24), 8711. [CrossRef]
96. 96. Barani, M., Rahdar, A., Mukhtar, M., Razzaq, S., Qindeel, M., Olam, S.A.H., Paiva-Santos, A.C., Ajalli, N., Sargazi, S., Balakrishnan, D. (2022). Recent application of cobalt ferrite nanoparticles as a theranostic agent. Materials Today Chemistry, 26, 101131. [CrossRef]
97. 97. Veloso, S.R., Magalhães, C.A., Rodrigues, A.R.O., Vilaça, H., Queiroz, M.J.R., Martins, J., Coutinho, P.J., Ferreira, P.M., Castanheira, E.M. (2019). Novel dehydropeptide-based magnetogels containing manganese ferrite nanoparticles as antitumor drug nanocarriers. Physical Chemistry Chemical Physics, 21(20), 10377-10390. [CrossRef]
98. 98. Veloso, S.R., Ferreira, P.M., Martins, J.A., Coutinho, P.J., Castanheira, E.M. (2018). Magnetogels: Prospects and main challenges in biomedical applications. Pharmaceutics, 10(3), 145. [CrossRef]
99. 99. Li, D.Q., Wang, S.Y., Meng, Y.J., Li, J.F., Li, J. (2020). An injectable, self-healing hydrogel system from oxidized pectin/chitosan/γ-Fe2O3. International Journal of Biological Macromolecules, 164, 4566-4574. [CrossRef]
100. 100. Gao, F., Xie, W., Miao, Y., Wang, D., Guo, Z., Ghosal, A., Li, Y., Wei, Y., Feng, S.S., Zhao, L. (2019). Magnetic hydrogel with optimally adaptive functions for breast cancer recurrence prevention. Advanced Healthcare Materials, 8(14), 1900203. [CrossRef]
101. 101. Versaw, B.A., Zeng, T., Hu, X., Robb, M.J. (2021). Harnessing the power of force: Development of mechanophores for molecular release. Journal of the American Chemical Society, 143(51), 21461-21473. [CrossRef]
102. 102. Kim, G., Lau, V.M., Halmes, A.J., Oelze, M.L., Moore, J.S., Li, K.C. (2019). High-intensity focused ultrasound-induced mechanochemical transduction in synthetic elastomers. Proceedings of the National Academy of Sciences, 116(21), 10214-10222. [CrossRef]
103. 103. Kim, G., Wu, Q., Chu, J.L., Smith, E.J., Oelze, M.L., Moore, J.S., Li, K.C. (2022). Ultrasound controlled mechanophore activation in hydrogels for cancer therapy. Proceedings of the National Academy of Sciences, 119(4), e2109791119. [CrossRef]
104. 104. Jo, Y.J., Gulfam, M., Jo, S.H., Gal, Y.S., Oh, C.W., Park, S.H., Lim, K.T. (2022). Multi-stimuli responsive hydrogels derived from hyaluronic acid for cancer therapy application. Carbohydrate Polymers, 286, 119303. [CrossRef]
105. 105. Zhao, L., Xu, J., Tong, Y., Gong, P., Gao, F., Li, H., Jiang, Y. (2022). Injectable “cocktail” hydrogel with dual‐stimuli‐responsive drug release, photothermal ablation, and drug‐antibody synergistic effect. SmartMat, 1-11 (Early view). [CrossRef]
106. 106. Zhu, Y., Wang, L., Li, Y., Huang, Z., Luo, S., He, Y., Han, H., Raza, F., Wu, J., Ge, L. (2020). Injectable pH and redox dual responsive hydrogels based on self-assembled peptides for anti-tumor drug delivery. Biomaterials Science, 8(19), 5415-5426. [CrossRef]