Micro and Nanogels for Biomedical Applications

Sahiner, Nurettin; CAN, Mehmet; Guven, Olgun

doi:10.15671/hjbc.810599

Micro and Nanogels for Biomedical Applications

Mehmet CAN, (Kimya Bölümü, Çanakkale Onsekiz Mart Üniversitesi, Çanakkale, Türkiye)

Olgun GUVEN, (Kimya Bölümü, Hacettepe Üniversitesi, Ankara, Türkiye.)

Nurettin SAHİNER (Kimya Bölümü, Çanakkale Onsekiz Mart Üniversitesi, Çanakkale, Türkiye)

Hacettepe Journal of Biology and Chemistry

6 0

Yıl: 2020 Cilt: 48 Sayı: 5 Sayfa Aralığı: 407 - 424 Metin Dili: İngilizce DOI: 10.15671/hjbc.810599 İndeks Tarihi: 29-06-2021

Micro and Nanogels for Biomedical Applications

Öz:

Micro and nano hydrogels developed from natural and synthetic polymers have garnered great deal of attention in scientific and industrial realms due to their higher surface area, degree of swelling and active material loading capacity,softness and flexibility, as well as their similarity to natural tissues. Particularly, biocompatible, non-toxic, and biodegradable micro/nano vehicles with tailor made design and functionalization facilitates their use with excellent feasibility for a variety of biomedical applications such as tissue engineering, bioimaging and drug delivery. However, these platforms requirerational design and functionalization strategies to cope with barriers of in vivo environment to pass into clinical use. Firstly,an ideal carrier should be biocompatible, and capable of evasion from immune elimination, specifically target at desiredsites and sustainably release the therapeutic cargo in response to microenvironment conditions. Despite the few setbacksin micro/nano vehicle design and several successful formulations translated to clinical use and majority of the carries areyet to achieve complete success for all biological criteria. In this review, design and functionalization strategies of micro andnanogels have been summarized. Also, the recent progress in biomedical applications of microgels and nanogels have beenoutlined with a primary focus placed on drug and biomolecule delivery applications.

Anahtar Kelime:

Biyomedikal Uygulamalar için Mikro ve Nanojeller

Öz:

Doğal ve sentetik polimerlerden geliştirilen mikro ve nano hidrojeller, yüksek yüzey alanı, yüksek derecede şişme, yüksek aktif madde yükleme kapasiteleri, yumuşaklık esneklik ve doğal dokulara benzerlikleri nedeniyle bilimsel ve endüstriyel alanda büyük ilgi görmüştür. Özellikle, biyouyumlu, toksik olmayan ve biyobozunur mikro/nano taşıyıcıların uygulamaya özgü tasarım ve fonksiyonelleştirilebilme olanakları, doku mühendisliği, biyo görüntüleme ve ilaç taşıma/teslim uygulamaları gibi çeşitli biyomedikal uygulamalar için mükemmel bir fizibilite sunmaktadır. Bununla birlikte, bu platformların in vivo ortamlardaki biyolojik bariyerleri aşabilmesi ve klinik uygulamalarda kullanıma girebilmesi için rasyonel tasarım ve işlevselleştirme stratejileri gerekmektedir. İlk olarak, ideal bir taşıyıcı biyo-uyumlu olmalı ve bağışıklık sisteminin eliminasyonundan kaçabilmeli, özellikle de istenen bölgeleri hedeflemeli ve ortam koşullarına duyarlı olarak terapötik yükü sürdürülebilir bir şekilde salabilmelidir. Mikro/nano materyal tasarımında küçük sorunlara rağmen klinik kullanıma giren birkaç başarılı formülasyon mevcuttur ve bu taşıyıcıların çoğu, tüm biyolojik kriterler için henüz tam bir başarı sağlayamamışlardır. Bu derlemede, mikro ve nanojellerin tasarım ve işlevselleştirme stratejileri özetlenerek mikro- ve nanojellerin biyomedikal uygulamalarındaki son gelişmeler, ilaç ve biyomolekül salım uygulamalarına ağırlık vererek özetlenmiştir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. H. Staudinger, Über polymerisation, Ber. Dtsch. Chem. Ges. (A B Ser.), 53 (1920) 1073-1085.
2. R. Mülhaupt, Hermann staudinger and the origin of macromolecular chemistry, Angew. Chem., Int. Ed., 43 (2004) 1054-1063.
3. H. Ringsdorf, Hermann staudinger and the future of polymer research jubilees—beloved occasions for cultural piety, Angew. Chem., Int. Ed., 43 (2004) 1064-1076.
4. M.H. Kim, G. Choi, A. Elzatahry, A. Vinu, Y.B. Choy, J.H. Choy, Review of clay-drug hybrid materials for biomedical applications: Administration routes, Clays Clay Miner., 64 (2016) 115-130.
5. C. Cha, S.R. Shin, N. Annabi, M.R. Dokmeci, A. Khademhosseini, Carbon-based nanomaterials: Multifunctional materials for biomedical engineering, ACS Nano, 7 (2013) 2891-2897.
6. M.C. Tan, G.M. Chow, L. Ren, Q. Zhang, Inorganic nanoparticles for biomedical applications, Nanosci. Biomed., Springer Berlin Heidelberg, Berlin, Heidelberg, vol? 2009 272-289.
7. H. Hatakeyama, H. Akita, H. Harashima, A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: A strategy for overcoming the PEG dilemma, Adv. Drug Delivery Rev., 63 (2011) 152- 160.
8. Y. Panahi, M. Farshbaf, M. Mohammadhosseini, M. Mirahadi, R. Khalilov, S. Saghfi, A. Akbarzadeh, Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications, Artif. Cells Nanomed. Biotechnol., 45 (2017) 788-799.
9. L. Nyström, A.A. Strömstedt, A. Schmidtchen, M. Malmsten, Peptide-loaded microgels as antimicrobial and antiinflammatory surface coatings, Biomacromolecules, 19 (2018) 3456-3466.
10. R. Nordström, L. Nyström, O.C.J. Andrén, M. Malkoch, A. Umerska, M. Davoudi, A. Schmidtchen, M. Malmsten, Membrane interactions of microgels as carriers of antimicrobial peptides, J. Colloid Interface Sci., 513 (2018) 141-150.
11. K.H. Bae, H.J. Chung, T.G. Park, Nanomaterials for cancer therapy and imaging, Mol. Cells, 31 (2011) 295-302.
12. H. Staudinger, E. Husemann, Über hochpolymere verbindungen, 116. Mitteil.: Über das begrenzt quellbare poly-styrol, Ber. Dtsch. Chem. Ges. (A B Ser.), 68 (1935) 1618-1634.
13. W. Funke, O. Okay, B. Joos-Müller, Microgels-intramolecularly crossünked macromolecules with a globular structure, in: microencapsul. microgels iniferters, Springer Berlin Heidelberg, Berlin, Heidelberg, n.d.: pp. 139–234.
14. W.O. Baker, Microgel, a new macromolecule, Ind. Eng. Chem. Res., 41 (1949) 511-520.
15. M. Tsintou, C. Wang, K. Dalamagkas, D. Weng, Y.-N. Zhang, W. Niu, Nanogels for biomedical applications: Drug delivery, imaging, tissue engineering, and biosensors, in: Nanobiomaterials Sci. Dev. Eval., Elsevier, 2017: pp. 87-124.
16. G. Agrawal, R. Agrawal, Functional microgels: Recent advances in their biomedical applications, Small., 14 (2018) 1801724.
17. Z. Shen, A. Mellati, J. Bi, H. Zhang, S. Dai, A thermally responsive cationic nanogel-based platform for threedimensional cell culture and recovery, RSC Adv., 4 (2014) 29146.
18. A.C. Daly, L. Riley, T. Segura, J.A. Burdick, Hydrogel microparticles for biomedical applications, Nat. Rev. Mater., 5 (2020) 20-43.
19. S.S. Suner, M. Şahiner, S.B. Şengel, D.J. Rees, W.F. Reed, N. Şahiner, Responsive biopolymer-based microgels/nanogels for drug delivery applications, in: Stimuli Responsive Polym. Nanocarriers Drug Deliv. Appl. Vol. 1, Elsevier, 2018: pp. 453- 500.
20. Narain, S. Asawa, V. Chhabria, Y. Patil-Sen, Cell membrane coated nanoparticles: next-generation therapeutics, Nanomedicine, 12 (2017) 2677-2692.
21. J.K. Oh, D.I. Lee, J.M. Park, Biopolymer-based microgels/ nanogels for drug delivery applications, Prog. Polym. Sci., 34 (2009) 1261-1282.
22. K. Akiyoshi, S. Deguchi, N. Moriguchi, S. Yamaguchi, J. Sunamoto, Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles, Macromolecules, 26 (1993) 3062-3068.
23. E. Mueller, R.J. Alsop, A. Scotti, M. Bleuel, M.C. Rheinstädter, W. Richtering, T. Hoare, Dynamically cross-linked selfassembled thermoresponsive microgels with homogeneous internal structures, Langmuir, 34 (2018) 1601-1612.
24. J. Varshosaz, S. Taymouri, E. Ghassami, Supramolecular selfassembled nanogels a new platform for anticancer drug delivery, Curr. Pharm. Des., 23 (2017) 5242-5260.
25. J.M. Myrick, V.K. Vendra, S. Krishnan, Self-assembled polysaccharide nanostructures for controlled-release applications, Nanotechnol. Rev. 3 (2014) page number?.
26. T. Zhang, R. Yang, S. Yang, J. Guan, D. Zhang, Y. Ma, H. Liu, Research progress of self-assembled nanogel and hybrid hydrogel systems based on pullulan derivatives, Drug Delivery, 25 (2018) 278-292.
27. T.V. Tran, T.H.D. Phuong, N.Q. Tran, C.K. Nguyen, D.H. Nguyen, Polymeric chitosan based nanogels as a potential platform for dual targeted drug delivery in cancer therapy, Int. J. Nanotechnol., 15 (2018) 188.
28. P. Pereira, S.S. Pedrosa, A. Correia, C.F. Lima, M.P. Olmedo, Á. González-Fernández, M. Vilanova, F.M. Gama, Biocompatibility of a self-assembled glycol chitosan nanogel, Toxicol. In Vitro, 29 (2015) 638-646.
29. L.C. Cheng, Y. Jiang, Y. Xie, L.L. Qiu, Q. Yang, H.Y. Lu, Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery, Oncotarget, 8 (2017) 3315-3326.
30. L.M. Bravo-Anaya, J.F.A. Soltero, M. Rinaudo, DNA/chitosan electrostatic complex, Int. J. Biol. Macromol., 88 (2016) 345- 353.
31. V. Chavasit, C. Kienzle-Sterzer, J. Antonio Torres, Formation and characterization of an insoluble polyelectrolyte complex: Chitosan-polyacrylic acid, Polym. Bull., 19 (1988) 223-230.
32. A.M. Alsharabasy, S.A. Moghannem, W.N. El-Mazny, Physical preparation of alginate/chitosan polyelectrolyte complexes for biomedical applications, J. Biomater. Appl., 30 (2016) 1071-1079.
33. T. Dai, S. Zhou, C. Yin, S. Li, W. Cao, W. Liu, K. Sun, H. Dou, Y. Cao, G. Zhou, Dextran-based fluorescent nanoprobes for sentinel lymph node mapping, Biomaterials, 35 (2014) 8227- 8235.
34. S. Zhou, X. Min, H. Dou, K. Sun, C.Y. Chen, C.T. Chen, Z. Zhang, Y. Jin, Z. Shen, Facile fabrication of dextran-based fluorescent nanogels as potential glucose sensors, Chem. Commun., 49 (2013) 9473.
35. O. Mezghrani, Y. Tang, X. Ke, Y. Chen, D. Hu, J. Tu, L. Zhao, N. Bourkaib, Hepatocellular carcinoma dually-targeted nanoparticles for reduction triggered intracellular delivery of doxorubicin, Int. J. Pharm., 478 (2015) 553-568.
36. S. Trombino, C. Servidio, F. Curcio, R. Cassano, Strategies for hyaluronic acid-based hydrogel design in drug delivery, Pharmaceutics, 11 (2019) 407.
37. Q. Feng, Q. Li, H. Wen, J. Chen, M. Liang, H. Huang, D. Lan, H. Dong, X. Cao, Injection and self-assembly of bioinspired stem cell-laden gelatin/hyaluronic acid hybrid microgels promote cartilage repair in vivo, Adv. Funct. Mater., 29 (2019) 1906690.
38. G. Huang, H. Huang, Application of hyaluronic acid as carriers in drug delivery, Drug Delivery, 25 (2018) 766-772.
39. Y.C. Kuo, C.H. Hsueh, Neuronal production from induced pluripotent stem cells in self-assembled collagen-hyaluronic acid-alginate microgel scaffolds with grafted GRGDSP/ Ln5-P4, Mater. Sci. Eng., C, 76 (2017) 760-774.
40. K. Zhao, D. Li, W. Xu, J. Ding, W. Jiang, M. Li, C. Wang, X. Chen, Targeted hydroxyethyl starch prodrug for inhibiting the growth and metastasis of prostate cancer, Biomaterials, 116 (2017) 82-94.
41. M. Kohri, Y. Nannichi, T. Taniguchi, K. Kishikawa, Biomimetic non-iridescent structural color materials from polydopamine black particles that mimic melanin granules, J. Mater. Chem. C, 3 (2015) 720-724.
42. W. Li, M. Yalcin, Q. Lin, M.-S.M. Ardawi, S.A. Mousa, Selfassembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery, J. Controlled Release, 248 (2017) 117-124.
43. J.E. Chung, S. Tan, S.J. Gao, N. Yongvongsoontorn, S.H. Kim, J.H. Lee, H.S. Choi, H. Yano, L. Zhuo, M. Kurisawa, J.Y. Ying, Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy, Nat. Nanotechnol., 9 (2014) 907-912.
44. Y.C. Chen, S.H. Yu, G.J. Tsai, D.W. Tang, F.L. Mi, Y.P. Peng, Novel technology for the preparation of self-assembled catechin/gelatin nanoparticles and their characterization, J. Agric. Food Chem., 58 (2010) 6728-6734.
45. Purwada, Y.F. Tian, W. Huang, K.M. Rohrbach, S. Deol, A. August, A. Singh, Self-assembly protein nanogels for safer cancer immunotherapy, Adv. Healthcare Mater., 5 (2016) 1413-1419.
46. T. Nishimura, A. Yamada, K. Umezaki, S. Sawada, S. Mukai, Y. Sasaki, K. Akiyoshi, Self-assembled polypeptide nanogels with enzymatically transformable surface as a small interfering rna delivery platform, Biomacromolecules, 18 (2017) 3913-3923.
47. W.T. Arab, A.M. Niyas, K. Seferji, H.H. Susapto, C.A.E. Hauser, Evaluation of peptide nanogels for accelerated wound healing in normal micropigs, Front. Nanosci. Nanotechnol. 4 (2018).
48. P. Chakraborty, E. Gazit, Amino acid based self-assembled nanostructures: Complex structures from remarkably simple building blocks, ChemNanoMat, 4 (2018) 730-740.
49. H.V.P. Thelu, S.K. Albert, M. Golla, N. Krishnan, D. Ram, S.M. Srinivasula, R. Varghese, Size controllable DNA nanogels from the self-assembly of DNA nanostructures through multivalent host–guest interactions, Nanoscale, 10 (2018) 222-230.
50. H. Xue, F. Ding, J. Zhang, Y. Guo, X. Gao, J. Feng, X. Zhu, C. Zhang, DNA tetrahedron-based nanogels for siRNA delivery and gene silencing, Chem. Commun., 55 (2019) 4222-4225.
51. N. Sanson, J. Rieger, Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization, Polym. Chem., 1 (2010) 965.
52. Y. Bin Hamzah, S. Hashim, W.A.W.A. Rahman, Synthesis of polymeric nano/microgels: A review, J. Polym. Res., 24 (2017) 134.
53. M. Matusiak, S. Kadlubowski, J.M. Rosiak, Nanogels synthesized by radiation-induced intramolecular crosslinking of water-soluble polymers, Radiat. Phys. Chem., 169 (2020) 108099.
54. M. Matusiak, S. Kadlubowski, P. Ulanski, Radiation-induced synthesis of poly(acrylic acid) nanogels, Radiat. Phys. Chem., 142 (2018) 125-129.
55. Adrian Alejandro Ges Naranjo, HerlysViltres Cobas, Danaydis Fonseca Rogdriguez, Manuel Rapado Paneque, Yuri Aguilera Corrales, Radiation-induced synthesis of polyvinylpyrrolidone (PVP) nanogels, J. Phys. Sci. Appl. 6 (2016) page number?.
56. K. Raghupathi, S.J. Eron, F. Anson, J.A. Hardy, S. Thayumanavan, Utilizing inverse emulsion polymerization to generate responsive nanogels for cytosolic protein delivery, Mol. Pharmaceutics, 14 (2017) 4515-4524.
57. S.F. Medeiros, A.M. Santos, H. Fessi, A. Elaissari, Synthesis of biocompatible and thermally sensitive poly(Nvinylcaprolactam) nanogels via inverse miniemulsion polymerization: Effect of the surfactant concentration, J. Polym. Sci., Part A: Polym. Chem., 48 (2010) 3932-3941.
58. C. Daubresse, C. Grandfils, R. Jerome, P. Teyssie, Enzyme immobilization in nanoparticles produced by inverse microemulsion polymerization, J. Colloid Interface Sci., 168 (1994) 222-229.
59. T. Madan, N. Munshi, T.K. De, A. Maitra, P. Usha Sarma, S.S. Aggarwal, Biodegradable nanoparticles as a sustained release system for the antigens/allergens of Aspergillus fumigatus: Preparation and characterisation, Int. J. Pharm., 159 (1997) 135-147.
60. D.J. Bharali, S.K. Sahoo, S. Mozumdar, A. Maitra, Crosslinked polyvinylpyrrolidone nanoparticles: A potential carrier for hydrophilic drugs, J. Colloid Interface Sci., 258 (2003) 415-423.
61. N. Şahiner, S. Demirci, Can PEI microgels become biocompatible upon betainization?, Mater. Sci. Eng., C., 77 (2017) 642-648.
62. T. Hoare, S. Young, M.W. Lawlor, D.S. Kohane, Thermoresponsive nanogels for prolonged duration local anesthesia, Acta Biomater., 8 (2012) 3596-3605.
63. N. Şahiner, S. Sağbaş, M. Türk, Poly(sucrose) micro particles preparation and their use as biomaterials, Int. J. Biol. Macromol., 66 (2014) 236-244.
64. M. Can, R.S. Ayyala, N. Şahiner, Crosslinked poly(Lactose) microgels and nanogels for biomedical applications, J. Colloid Interface Sci., 553 (2019) 805-812.
65. M.A. Pujana, L. Pérez-Álvarez, L.C. Cesteros Iturbe, I. Katime, Water dispersible pH-responsive chitosan nanogels modified with biocompatible crosslinking-agents, Polymer, 53 (2012) 3107-3116.
66. N. Şahiner, S. Sağbaş, H. Yoshida, L.A. Lyon, Synthesis and properties of inulin based microgels, Colloids Interface Sci. Commun., 2 (2014) 15-18.
67. H. Su, Q. Jia, S. Shan, Synthesis and characterization of Schiff base contained dextran microgels in water-in-oil inverse microemulsion, Carbohydr. Polym., 152 (2016) 156-162.
68. E. Jooybar, M.J. Abdekhodaie, P.J. Dijkstra, Synthesis of hyaluronic acid-tyramine microgels for sustained protein release, in: 2018 25th Natl. 3rd Int. Iran. Conf. Biomed. Eng., IEEE, 2018: pp. 1-5.
69. N. Şahiner, S.S. Suner, R.S. Ayyala, Mesoporous, degradable hyaluronic acid microparticles for sustainable drug delivery application, Colloids Surf., B, 177 (2019) 284-293.
70. S. Bütün, F.G. İnce, H. Erduğan, N. Şahiner, One-step fabrication of biocompatible carboxymethyl cellulose polymeric particles for drug delivery systems, Carbohydr. Polym., 86 (2011) 636-643.
71. Y. Ke, G.S. Liu, J.H. Wang, W. Xue, C. Du, G. Wu, Preparation of carboxymethyl cellulose based microgels for cell encapsulation, eXPRESS Polym. Lett., 8 (2014) 841-849.
72. S.S. Suner, N. Sahiner, Biocompatible macro, micro and nano scale guar gum hydrogels and their protein absorption capacity, J. Macromol. Sci. Part A. (2020) 1–9. https://doi.or g/10.1080/10601325.2020.1787844.
73. N. Şahiner, S. Sağbaş, N. Aktaş, C. Silan, Inherently antioxidant and antimicrobial tannic acid release from poly(tannic acid) nanoparticles with controllable degradability, Colloids Surf., B, 142 (2016) 334-343.
74. M. Şahiner, N. Şahiner, S. Sağbaş, M.L. Fullerton, D.A. Blake, Fabrication of biodegradable poly(naringin) particles with antioxidant activity and low toxicity, ACS Omega, 3 (2018) 17359-17367.
75. N. Şahiner, One step poly(quercetin) particle preparation as biocolloid and its characterization, Colloids Surf., A, 452 (2014) 173-180.
76. N. Şahiner, One step poly(rutin) particle preparation as biocolloid and its characterization, Mater. Sci. Eng., C, 44 (2014) 9-16.
77. N. Wang, X. Cheng, N. Li, H. Wang, H. Chen, Nanocarriers and their loading strategies, Adv. Healthcare Mater., 8 (2019) 1801002.
78. J.M. Morachis, E.A. Mahmoud, A. Almutairi, Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles, Pharmacol. Rev., 64 (2012) 505- 519.
79. N. Şahiner, S. Sağbaş, S. Yılmaz, Microgels derived from different forms of carrageenans, kappa, iota, and lambda for biomedical applications, MRS Adv., 2 (2017) 2521-2527.
80. G. Pasut, F.M. Veronese, Polymer–drug conjugation, recent achievements and general strategies, Prog. Polym. Sci., 32 (2007) 933-961.
81. Y.R. Choi, H. J. Kim, G.Y. Ahn, M.J. Lee, J.R. Park, D.R. Jun, T.K. Ryu, J.W. Park, E. Shin, S.W. Choi, Fabrication of dihydroxyflavoneconjugated hyaluronic acid nanogels for targeted antitumoral effect, Colloids Surf., B, 171 (2018) 690-697.
82. J.P. Nam, S.C. Park, T.H. Kim, J.Y. Jang, C. Choi, M.K. Jang, J.W. Nah, Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery, Int. J. Pharm., 457 (2013) 124-135.
83. E. Mauri, G. Perale, F. Rossi, Nanogel functionalization: A versatile approach to meet the challenges of drug and gene delivery, ACS Appl. Nano Mater., 1 (2018) 6525-6541.
84. N.H. Abd Ellah, S.A. Abouelmagd, Surface functionalization of polymeric nanoparticles for tumor drug delivery: Approaches and challenges, Expert Opin. Drug Deliv., 14 (2017) 201-214.
85. Z. Amoozgar, Y. Yeo, Recent advances in stealth coating of nanoparticle drug delivery systems, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 4 (2012) 219-233.
86. M. Noga, D. Edinger, W. Rödl, E. Wagner, G. Winter, A. Besheer, Controlled shielding and deshielding of gene delivery polyplexes using hydroxyethyl starch (HES) and alpha-amylase, J. Controlled Release, 159 (2012) 92-103.
87. Z. Amoozgar, J. Park, Q. Lin, Y. Yeo, Low molecular-weight chitosan as a ph-sensitive stealth coating for tumor-specific drug delivery, Mol. Pharmaceutics, 9 (2012) 1262-1270.
88. L. Cui, Q. Lin, C.S. Jin, W. Jiang, H. Huang, L. Ding, N. Muhanna, J.C. Irish, F. Wang, J. Chen, G. Zheng, A PEGylation-free biomimetic porphyrin nanoplatform for personalized cancer theranostics, ACS Nano, 9 (2015) 4484-4495.
89. P.L. Rodriguez, T. Harada, D.A. Christian, D.A. Pantano, R.K. Tsai, D.E. Discher, Minimal “self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles, Science, 339 (2013) 971-975.
90. C.M.J. Hu, L. Zhang, S. Aryal, C. Cheung, R.H. Fang, L. Zhang, Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform, Proc. Natl. Acad. Sci. U.S.A., 108 (2011) 10980-10985.
91. M. Wu, W. Le, T. Mei, Y. Wang, B. Chen, Z. Liu, C. Xue, Cell membrane camouflaged nanoparticles: a new biomimetic platform for cancer photothermal therapy, Int. J. Nanomed., 14 (2019) 4431-4448.
92. R. Li, Y. He, S. Zhang, J. Qin, J. Wang, Cell membranebased nanoparticles: a new biomimetic platform for tumor diagnosis and treatment, Acta Pharm. Sin. B., 8 (2018) 14-22.
93. C. Gao, Z. Lin, B. Jurado-Sánchez, X. Lin, Z. Wu, Q. He, Stem cell membrane-coated nanogels for highly efficient in vivo tumor targeted drug delivery, Small, 12 (2016) 4056-4062.
94. T.M. Allen, Ligand-targeted therapeutics in anticancer therapy, Nat. Rev. Cancer, 2 (2002) 750-763.
95. W.X. Ren, J. Han, S. Uhm, Y.J. Jang, C. Kang, J.H. Kim, J.S. Kim, Recent development of biotin conjugation in biological imaging, sensing, and target delivery, Chem. Commun., 51 (2015) 10403-10418.
96. S. Jain, G. Spandana, A.K. Agrawal, V. Kushwah, K. Thanki, Enhanced antitumor efficacy and reduced toxicity of docetaxel loaded estradiol functionalized stealth polymeric nanoparticles, Mol. Pharmaceutics, 12 (2015) 3871-3884.
97. M. Li, Z. Tang, Y. Zhang, S. Lv, Q. Li, X. Chen, Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis, Acta Biomater., 18 (2015) 132-143.
98. J. Li, D.J. Mooney, Designing hydrogels for controlled drug delivery, Nat. Rev. Mater., 1 (2016) 16071.
99. Y. Wang, D.S. Kohane, External triggering and triggered targeting strategies for drug delivery, Nat. Rev. Mater., 2 (2017) 17020.
100. M.A.C. Stuart, W.T.S. Huck, J. Genzer, M. Müller, C. Ober, M. Stamm, G.B. Sukhorukov, I. Szleifer, V. V. Tsukruk, M. Urban, F. Winnik, S. Zauscher, I. Luzinov, S. Minko, Emerging applications of stimuli-responsive polymer materials, Nat. Mater., 9 (2010) 101-113.
101. S. Mitragotri, P.A. Burke, R. Langer, Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies, Nat. Rev. Drug Discovery, 13 (2014) 655-672.
102. M. Vicario-de-la-Torre, J. Forcada, The potential of stimuliresponsive nanogels in drug and active molecule delivery for targeted therapy, Gels, 3 (2017) 16.
103. Q.M. Zhang, W. Wang, Y.-Q. Su, E.J.M. Hensen, M.J. Serpe, Biological imaging and sensing with multiresponsive microgels, Chem. Mater., 28 (2016) 259-265.
104. X. Li, X. Su, Multifunctional smart hydrogels: Potential in tissue engineering and cancer therapy, J. Mater. Chem. B., 6 (2018) 4714-4730.
105. F. Danhier, O. Feron, V. Préat, To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery, J. Controlled Release, 148 (2010) 135-146.
106. P. Wei, G. Gangapurwala, D. Pretzel, M.N. Leiske, L. Wang, S. Hoeppener, S. Schubert, J.C. Brendel, U.S. Schubert, Smart pH-sensitive nanogels for controlled release in an acidic environment, Biomacromolecules, 20 (2019) 130-140.
107. Y.J. Pan, D. Li, S. Jin, C. Wei, K.Y. Wu, J. Guo, C.C. Wang, Folateconjugated poly(N-(2-hydroxypropyl)methacrylamide-comethacrylic acid) nanohydrogels with pH/redox dual-stimuli response for controlled drug release, Polym. Chem., 4 (2013) 3545.
108. N. Deirram, C. Zhang, S.S. Kermaniyan, A.P.R. Johnston, G.K. Such, pH-responsive polymer nanoparticles for drug delivery, Macromol. Rapid Commun., 40 (2019) 1800917.
109. S. Luan, Y. Zhu, X. Wu, Y. Wang, F. Liang, S. Song, Hyaluronicacid-based ph-sensitive nanogels for tumor-targeted drug delivery, ACS Biomater. Sci. Eng., 3 (2017) 2410-2419.
110. L. Ding, Y. Jiang, J. Zhang, H.A. Klok, Z. Zhong, pH-sensitive coiled-coil peptide-cross-linked hyaluronic acid nanogels: synthesis and targeted intracellular protein delivery to CD44 positive cancer cells, Biomacromolecules, 19 (2018) 555-562.
111. H.V.P. Thelu, S. Atchimnaidu, D. Perumal, K.S. Harikrishnan, S. Vijayan, R. Varghese, Self-assembly of an aptamerdecorated, dna–protein hybrid nanogel: A biocompatible nanocarrier for targeted cancer therapy, ACS Appl. Bio Mater., 2 (2019) 5227-5234.
112. N.M. Oh, K.T. Oh, Y.S. Youn, D.-K. Lee, K.H. Cha, D.H. Lee, E.S. Lee, Poly(l-aspartic acid) nanogels for lysosome-selective antitumor drug delivery, Colloids Surf., B, 101 (2013) 298- 306.
113. J. Siirilä, S. Hietala, F.S. Ekholm, H. Tenhu, Glucose and maltose surface-functionalized thermoresponsive poly( N -Vinylcaprolactam) nanogels, Biomacromolecules, 21 (2020) 955-965.
114. L.Y. Chu, J.W. Kim, R.K. Shah, D.A. Weitz, Monodisperse thermoresponsive microgels with tunable volume-phase transition kinetics, Adv. Funct. Mater., 17 (2007) 3499-3504.
115. S. Ghaeini-Hesaroeiye, H. Razmi Bagtash, S. Boddohi, E. Vasheghani-Farahani, E. Jabbari, Thermoresponsive nanogels based on different polymeric moieties for biomedical applications, Gels. 6 (2020) 20.
116. L.A. Lyon, Z. Meng, N. Singh, C.D. Sorrell, A. St. John, Thermoresponsive microgel-based materials, Chem. Soc. Rev., 38 (2009) 865.
117. K. Sudhakar, K. Madhusudana Rao, M.C.S. Subha, K. Chowdoji Rao, E.R. Sadiku, Temperature-responsive poly( N -vinylcaprolactam-co-hydroxyethyl methacrylate) nanogels for controlled release studies of curcumin, Des. Monomers Polym., 18 (2015) 705-713.
118. H.G. Schild, Poly(N-isopropylacrylamide): Experiment, theory and application, Prog. Polym. Sci., 17 (1992) 163-249.
119. B. Zhang, S. Sun, P. Wu, Synthesis and unusual volume phase transition behavior of poly(N-isopropylacrylamide)–poly(2- hydroxyethyl methacrylate) interpenetrating polymer network microgel, Soft Matter, 9 (2013) 1678-1684.
120. Schwerdt, A. Zintchenko, M. Concia, N. Roesen, K.D. Fisher, L.H. Lindner, R.D. Issels, E. Wagner, M. Ogris, Hyperthermia induced targeting of thermosensitive gene carriers to tumors, Hum. Gene Ther., (2008) 081015093227032.
121. N.S. Rejinold, K.P. Chennazhi, S.V. Nair, H. Tamura, R. Jayakumar, Biodegradable and thermo-sensitive chitosan-gpoly(N-vinylcaprolactam) nanoparticles as a 5-fluorouracil carrier, Carbohydr. Polym., 83 (2011) 776-786.
122. A.L. Daniel-da-Silva, L. Ferreira, A.M. Gil, T. Trindade, Synthesis and swelling behavior of temperature responsive κ-carrageenan nanogels, J. Colloid Interface Sci., 355 (2011) 512-517.
123. X. Li, W. Yuan, S. Gu, J. Ren, Synthesis and self-assembly of tunable thermosensitive chitosan amphiphilic copolymers by click chemistry, Mater. Lett., 64 (2010) 2663-2666.
124. W. Lv, S. Liu, W. Feng, J. Qi, G. Zhang, F. Zhang, X. Fan, Temperature- and redox-directed multiple self assembly of poly( N -Isopropylacrylamide) grafted dextran nanogels, Macromol. Rapid Commun., 32 (2011) 1101-1107.
125. T. Fernandes Stefanello, A. Szarpak-Jankowska, F. Appaix, B. Louage, L. Hamard, B.G. De Geest, B. van der Sanden, C.V. Nakamura, R. Auzély-Velty, Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages, Acta Biomater., 10 (2014) 4750-4758.
126. S. Ekici, P. Ilgin, S. Yilmaz, N. Aktaş, N. Şahiner, Temperature and magnetic field responsive hyaluronic acid particles with tunable physical and chemical properties, Appl. Surf. Sci., 257 (2011) 2669-2676.
127. Y. Xia, X. He, M. Cao, C. Chen, H. Xu, F. Pan, J.R. Lu, Thermoresponsive microgel films for harvesting cells and cell sheets, Biomacromolecules, 14 (2013) 3615-3625.
128. Q. Luo, P. Liu, Y. Guan, Y. Zhang, Thermally induced phase transition of glucose-sensitive core−shell microgels, ACS Appl. Mater. Interfaces, 2 (2010) 760-767.
129. K. Fujimoto, T. Takahashi, M. Miyaki, H. Kawaguchi, Cell activation by the micropatterned surface with settling particles, J. Biomater. Sci., Polym. Ed., 8 (1997) 879-891.
130. H. Wang, J. Yi, S. Mukherjee, P. Banerjee, S. Zhou, Magnetic/ NIR-thermally responsive hybrid nanogels for optical temperature sensing, tumor cell imaging and triggered drug release, Nanoscale, 6 (2014) 13001-13011.
131. M.D. Krebs, R.M. Erb, B.B. Yellen, B. Samanta, A. Bajaj, V.M. Rotello, E. Alsberg, Formation of ordered cellular structures in suspension via label-free negative magnetophoresis, Nano Lett., 9 (2009) 1812-1817.
132. E.A. Lee, H. Yim, J. Heo, H. Kim, G. Jung, N.S. Hwang, Application of magnetic nanoparticle for controlled tissue assembly and tissue engineering, Arch. Pharmacal Res., 37 (2014) 120-128.
133. H. Perea, J. Aigner, J.T. Heverhagen, U. Hopfner, E. Wintermantel, Vascular tissue engineering with magnetic nanoparticles: seeing deeper, J. Tissue Eng. Regener. Med., 1 (2007) 318-321.
134. A.M. Pavlov, B.G. De Geest, B. Louage, L. Lybaert, S. De Koker, Z. Koudelka, A. Sapelkin, G.B. Sukhorukov, Magnetically engineered microcapsules as intracellular anchors for remote control over cellular mobility, Adv. Mater., 25 (2013) 6945-6950.
135. L.J.D. Valle, A. Díaz, J. Puiggalí, Hydrogels for biomedical applications: Cellulose, chitosan, and protein/peptide derivatives, Gels. 3 (2017) 27.
136. E. Jooybar, M.J. Abdekhodaie, M. Karperien, A. Mousavi, M. Alvi, P.J. Dijkstra, Developing hyaluronic acid microgels for sustained delivery of platelet lysate for tissue engineering applications, Int. J. Biol. Macromol., 144 (2020) 837-846.
137. L. Kumar Meena, H. Rather, D. Kedaria, R. Vasita, Polymeric microgels for bone tissue engineering applications – a review, Int. J. Polym. Mater. Polym. Biomater., 69 (2020) 381-397.
138. J.P. Newsom, K.A. Payne, M.D. Krebs, Microgels: Modular, tunable constructs for tissue regeneration, Acta Biomater., 88 (2019) 32-41.
139. M. Fan, J. Yan, H. Tan, Y. Miao, X. Hu, Magnetic biopolymer nanogels via biological assembly for vectoring delivery of biopharmaceuticals, J. Mater. Chem. B, 2 (2014) 8399-8405.
140. Q. Zhang, J. Colazo, D. Berg, S.M. Mugo, M.J. Serpe, Multiresponsive nanogels for targeted anticancer drug delivery, Mol. Pharmaceutics, 14 (2017) 2624-2628.
141. S. Lou, S. Gao, W. Wang, M. Zhang, J. Zhang, C. Wang, C. Li, D. Kong, Q. Zhao, Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery, Nanoscale, 7 (2015) 3137-3146.
142. R.B.K.C., B. Thapa, P. Xu, pH and redox dual responsive nanoparticle for nuclear targeted drug delivery, Mol. Pharmaceutics, 9 (2012) 2719-2729.
143. H. Yang, Q. Wang, S. Huang, A. Xiao, F. Li, L. Gan, X. Yang, Smart pH/redox dual-responsive nanogels for on-demand intracellular anticancer drug release, ACS Appl. Mater. Interfaces, 8 (2016) 7729-7738.
144. D. Zhou, S. Liu, Y. Hu, S. Yang, B. Zhao, K. Zheng, Y. Zhang, P. He, G. Mo, Y. Li, Tumor-mediated shape-transformable nanogels with pH/redox/enzymatic-sensitivity for anticancer therapy, J. Mater. Chem. B, 8 (2020) 3801-3813.
145. F. Mahmoodzadeh, M. Ghorbani, B. Jannat, Glutathione and pH-responsive chitosan-based nanogel as an efficient nanoplatform for controlled delivery of doxorubicin, J. Drug Delivery Sci. Technol, 54 (2019) 101315.
146. F. Li, H. Yang, N. Bie, Q. Xu, T. Yong, Q. Wang, L. Gan, X. Yang, Zwitterionic temperature/redox-sensitive nanogels for nearinfrared light-triggered synergistic thermo-chemotherapy, ACS Appl. Mater. Interfaces, 9 (2017) 23564-23573.
147. D. Han, X. Tong, Y. Zhao, Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation, Langmuir, 28 (2012) 2327-2331.
148. Z. Cao, X. Zhou, G. Wang, Selective release of hydrophobic and hydrophilic cargos from multi-stimuli-responsive nanogels, ACS Appl. Mater. Interfaces, 8 (2016) 28888- 28896.
149. Digital Human for Drug Development (DHD2) (2014) [cited August, 2020] available at http://xtal.ipph.purdue.edu/ DHD2/

APA	CAN M, Guven O, Sahiner N (2020). Micro and Nanogels for Biomedical Applications. , 407 - 424. 10.15671/hjbc.810599
Chicago	CAN Mehmet,Guven Olgun,Sahiner Nurettin Micro and Nanogels for Biomedical Applications. (2020): 407 - 424. 10.15671/hjbc.810599
MLA	CAN Mehmet,Guven Olgun,Sahiner Nurettin Micro and Nanogels for Biomedical Applications. , 2020, ss.407 - 424. 10.15671/hjbc.810599
AMA	CAN M,Guven O,Sahiner N Micro and Nanogels for Biomedical Applications. . 2020; 407 - 424. 10.15671/hjbc.810599
Vancouver	CAN M,Guven O,Sahiner N Micro and Nanogels for Biomedical Applications. . 2020; 407 - 424. 10.15671/hjbc.810599
IEEE	CAN M,Guven O,Sahiner N "Micro and Nanogels for Biomedical Applications." , ss.407 - 424, 2020. 10.15671/hjbc.810599
ISNAD	CAN, Mehmet vd. "Micro and Nanogels for Biomedical Applications". (2020), 407-424. https://doi.org/10.15671/hjbc.810599

APA	CAN M, Guven O, Sahiner N (2020). Micro and Nanogels for Biomedical Applications. Hacettepe Journal of Biology and Chemistry, 48(5), 407 - 424. 10.15671/hjbc.810599
Chicago	CAN Mehmet,Guven Olgun,Sahiner Nurettin Micro and Nanogels for Biomedical Applications. Hacettepe Journal of Biology and Chemistry 48, no.5 (2020): 407 - 424. 10.15671/hjbc.810599
MLA	CAN Mehmet,Guven Olgun,Sahiner Nurettin Micro and Nanogels for Biomedical Applications. Hacettepe Journal of Biology and Chemistry, vol.48, no.5, 2020, ss.407 - 424. 10.15671/hjbc.810599
AMA	CAN M,Guven O,Sahiner N Micro and Nanogels for Biomedical Applications. Hacettepe Journal of Biology and Chemistry. 2020; 48(5): 407 - 424. 10.15671/hjbc.810599
Vancouver	CAN M,Guven O,Sahiner N Micro and Nanogels for Biomedical Applications. Hacettepe Journal of Biology and Chemistry. 2020; 48(5): 407 - 424. 10.15671/hjbc.810599
IEEE	CAN M,Guven O,Sahiner N "Micro and Nanogels for Biomedical Applications." Hacettepe Journal of Biology and Chemistry, 48, ss.407 - 424, 2020. 10.15671/hjbc.810599
ISNAD	CAN, Mehmet vd. "Micro and Nanogels for Biomedical Applications". Hacettepe Journal of Biology and Chemistry 48/5 (2020), 407-424. https://doi.org/10.15671/hjbc.810599