journal article·2022-07

A review on structure, preparation and applications of silk fibroin-based nano-drug delivery systems

Praharsh Kumar Mandadhi Rajendra, Bala Sai Soujith Nidamanuri, Anjali Puthusserikkunnu Balan, Senthil Venkatachalam, Natarajan Jawahar

Journal of Nanoparticle Research· Volume 24· Issue 7
Publisher page

Abstract

The development of highly effective systems for drug delivery is crucial in biomedical care. Protein-based carriers have gained more importance in drug delivery as they are more advantageous than conventional drug delivery systems. Silk fibroin is a naturally occurring protein derived from cocoons of Bombyx mori. It has high potential in biomedical fields for its excellent biocompatibility and biodegradability. Due to its unique properties, it is highly capable of loading and delivering various biomolecules, drugs and other moieties as therapeutics. Many emphases have been directed to develop SF-based nano-drug delivery for its strong binding capacity for a wide range of drugs, controlled drug release characteristics, and ease of fabrication. The recent developments on SF-based nanoparticles have been highlighted in this review, covering SF’s chemical structure, properties and preparation methods. Also, recent functions of SF for the fabrication of nano-drug delivery systems are discussed. Graphical abstract
Source: expertdata · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Silk-based biomaterials and applications · Polymer Surface Interaction Studies · Biochemical and Structural Characterization

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (100+)

Show source-provided references
1. Jahanshahi M, Babaei Z (2008) Protein nanoparticle: a unique system as drug delivery vehicles. Afr J Biotechnol 7(25):4926–4934
2. Tian Y, Jiang X, Chen X, Shao Z, Yang W (2014) Doxorubicin-loaded magnetic silk fibroin nanoparticles for targeted therapy of multidrug-resistant cancer. Adv Mater 26(43):7393–739810.1002/adma.201403562 ↗
3. Tao H, Kaplan DL, Omenetto FG (2012) Silk materials - a road to sustainable high technology. Adv Mater 24(21):2824–283710.1002/adma.201104477 ↗
4. Jin HJ, Kaplan DL (2003) Mechanism of silk processing in insects and spiders. Nature 424(6952):1057–106110.1038/nature01809 ↗
5. Yan HB, Zhang YQ, Ma YL, Zhou LX (2009) Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system. J Nanopart Res 11(8):1937–194610.1007/s11051-008-9549-y ↗
6. Cheema SK, Gobin AS, Rhea R, Lopez-Berestein G, Newman RA, Mathur AB (2007) Silk fibroin mediated delivery of liposomal emodin to breast cancer cells. Int J Pharm 341(1–2):221–22910.1016/j.ijpharm.2007.03.043 ↗
7. Mottaghitalab F, Farokhi M, Shokrgozar MA, Atyabi F, Hosseinkhani H (2015) Silk fibroin nanoparticle as a novel drug delivery system. J Control Release 206:161–17610.1016/j.jconrel.2015.03.020 ↗
8. Ling S, Chen W, Fan Y, Zheng K, Jin K, Yu H et al (2018) Biopolymer nanofibrils: structure, modeling, preparation, and applications. Prog Polym Sci 85:1–5610.1016/j.progpolymsci.2018.06.004 ↗
9. Inoue S, Tanaka K, Arisaka F, Kimura S, Ohtomo K, Mizuno S (2000) Silk fibroin of Bombyx mori Is secreted, assembling a high molecular mass elementary unit consisting of H-chain, L-chain, and P25, with a 6:6:1 molar ratio. J Biol Chem 275(51):40517–4052810.1074/jbc.M006897200 ↗
10. Numata K, Ifuku N, Masunaga H, Hikima T, Sakai T (2017) Silk Resin with hydrated dual chemical-physical cross-links achieves high strength and toughness. Biomacromol 18(6):1937–194610.1021/acs.biomac.7b00376 ↗
11. Nguyen AT, Huang Q-L, Yang Z, Lin N, Xu G, Liu XY (2015) Crystal networks in silk fibrous materials: from hierarchical structure to ultra performance. Small 11(9–10):1039–105410.1002/smll.201402985 ↗
12. Liu R, Deng Q, Yang Z, Yang D, Han M-Y, Liu XY (2016) “Nano-fishnet” structure making silk fibers tougher. Adv Funct Mater 26(30):5534–554110.1002/adfm.201600813 ↗
13. Asakura T, Okushita K, Williamson MP (2015) Analysis of the structure of Bombyx mori silk fibroin by NMR. Macromolecules 48(8):2345–235710.1021/acs.macromol.5b00160 ↗
14. Valluzzi R, Gido SP, Muller W, Kaplan DL (1999) Orientation of silk III at the air-water interface. Int J Biol Macromol 24(2–3):237–24210.1016/S0141-8130(99)00002-1 ↗
15. Shao Z, Vollrath F (2002) Surprising strength of silkworm silk. Nature 418(6899):741–74110.1038/418741a ↗
16. Koh L-D, Cheng Y, Teng C-P, Khin Y-W, Loh X-J, Tee S-Y et al (2015) Structures, mechanical properties and applications of silk fibroin materials. Prog Polym Sci 46:86–11010.1016/j.progpolymsci.2015.02.001 ↗
17. Römer L, Scheibel T (2008) The elaborate structure of spider silk: structure and function of a natural high performance fiber. Prion 2(4):154–16110.4161/pri.2.4.7490 ↗
18. Keten S, Xu Z, Ihle B, Buehler MJ (2010) Nanoconfinement controls stiffness, strength and mechanical toughness of β-sheet crystals in silk. Nature Mater 9(4):359–36710.1038/nmat2704 ↗
19. Nuanchai K, Wilaiwan S, Prasong S (2010) Effect of different organic solvents and treatment times on secondary structure and thermal properties of silk fibroin films. Curr Res Chem 1:1–9
20. Sashina ES, Bochek AM, Novoselov NP, Kirichenko DA (2006) Structure and solubility of natural silk fibroin. Russ J Appl Chem 79(6):869–87610.1134/S1070427206060012 ↗
21. Williams DF (2008) On the mechanisms of biocompatibility. Biomaterials 29(20):2941–295310.1016/j.biomaterials.2008.04.023 ↗
22. Holland C, Numata K, Rnjak-Kovacina J, Seib FP (2019) The Biomedical use of silk: past, present, future. Adv Healthcare Mater 8(1):180046510.1002/adhm.201800465 ↗
23. Kundu B, Rajkhowa R, Kundu SC, Wang X (2013) Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev 65(4):457–47010.1016/j.addr.2012.09.043 ↗
24. Wang Y, Rudym DD, Walsh A, Abrahamsen L, Kim H-J, Kim HS et al (2008) In vivo degradation of three-dimensional silk fibroin scaffolds. Biomaterials 29(24–25):3415–342810.1016/j.biomaterials.2008.05.002 ↗
25. Thurber AE, Omenetto FG, Kaplan DL (2015) In vivo bioresponses to silk proteins. Biomaterials 71:145–15710.1016/j.biomaterials.2015.08.039 ↗
26. Cao Y, Wang B (2009) Biodegradation of silk biomaterials. IJMS 10(4):1514–152410.3390/ijms10041514 ↗
27. Nguyen TP, Nguyen QV, Nguyen V-H, Le T-H, Huynh VQN, Vo D-VN et al (2019) Silk fibroin-based biomaterials for biomedical applications: a review. Polymers 11(12):193310.3390/polym11121933 ↗
28. Zhang Y-Q, Shen W-D, Xiang R-L, Zhuge L-J, Gao W-J, Wang W-B (2007) Formation of silk fibroin nanoparticles in water-miscible organic solvent and their characterization. J Nanopart Res 9(5):885–90010.1007/s11051-006-9162-x ↗
29. Montalbán MG, Carissimi G, Lozano-Pérez AA, Cenis JL, Coburn JM, Kaplan DL, Víllora G (2018) Biopolymeric nanoparticle synthesis in ionic liquids. Recent Adv Ionic Liq, pp 3–2610.5772/intechopen.78766 ↗
30. Xie F, Zhang H, Shao H, Hu X (2006) Effect of shearing on formation of silk fibers from regenerated Bombyx mori silk fibroin aqueous solution. Int J Biol Macromol 38(3–5):284–28810.1016/j.ijbiomac.2006.03.021 ↗
31. Zhou P, Xie X, Knight DP, Zong X-H, Deng F, Yao W-H (2004) Effects of pH and calcium ions on the conformational transitions in silk fibroin using 2D Raman correlation spectroscopy and 13C solid-state NMR. Biochemistry 43(35):11302–1131110.1021/bi049344i ↗
32. Percot A, Colomban P, Paris C, Dinh HM, Wojcieszak M, Mauchamp B (2014) Water dependent structural changes of silk from Bombyx mori gland to fibre as evidenced by Raman and IR spectroscopies. Vib Spectrosc 73:79–8910.1016/j.vibspec.2014.05.004 ↗
33. Carissimi G, Baronio CM, Montalbán MG, Víllora G, Barth A (2020) On the secondary structure of silk fibroin nanoparticles obtained using ionic liquids: an infrared spectroscopy study. Polymers 12(6):129410.3390/polym12061294 ↗
34. Rockwood DN, Preda RC, Yücel T, Wang X, Lovett ML, Kaplan DL (2011) Materials fabrication from Bombyx mori silk fibroin. Nat Protoc 6(10):1612–163110.1038/nprot.2011.379 ↗
35. Tomeh MA, Hadianamrei R, Zhao X (2019) Silk fibroin as a functional biomaterial for drug and gene delivery. Pharmaceutics 11(10):49410.3390/pharmaceutics11100494 ↗
36. Myung SJ, Kim H-S, Kim Y, Chen P, Jin H-J (2008) Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion. Macromol Res 16(7):604–60810.1007/BF03218567 ↗
37. Qu J, Liu Y, Yu Y, Li J, Luo J, Li M (2014 Nov) Silk fibroin nanoparticles prepared by electrospray as controlled release carriers of cisplatin. Mater Sci Eng, C 44:166–17410.1016/j.msec.2014.08.034 ↗
38. Zhao Z, Li Y, Chen A-Z, Zheng Z-J, Hu J-Y, Li J-S et al (2013) Generation of silk fibroin nanoparticles via solution-enhanced dispersion by supercritical CO2. Ind Eng Chem Res 52(10):3752–376110.1021/ie301907f ↗
39. Zhao Z, Li Y, Xie M-B (2015) Silk Fibroin-based nanoparticles for drug delivery. IJMS 16(3):4880–490310.3390/ijms16034880 ↗
40. Lammel AS, Hu X, Park S-H, Kaplan DL, Scheibel TR (2010) Controlling silk fibroin particle features for drug delivery. Biomaterials 31(16):4583–459110.1016/j.biomaterials.2010.02.024 ↗
41. Lohcharoenkal W, Wang L, Chen YC, Rojanasakul Y (2014) Protein nanoparticles as drug delivery carriers for cancer therapy. Biomed Res Int 2014:1–1210.1155/2014/180549 ↗
42. Pinto Reis C, Neufeld RJ, Ribeiro AJ, Veiga F (2006) Nanoencapsulation I Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed: Nanotechnol Biol Med. 2(1):8–2110.1016/j.nano.2005.12.003 ↗
43. Wu Y, MacKay JA, McDaniel JR, Chilkoti A, Clark RL (2009 Jan 12) Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying. Biomacromol 10(1):19–2410.1021/bm801033f ↗
44. Jaworek A, Sobczyk AT (2008) Electrospraying route to nanotechnology: an overview. J Electrostat 66(3–4):197–21910.1016/j.elstat.2007.10.001 ↗
45. Ekwall P, Mandell L, Solyom P (1971) The solution phase with reversed micelles in the cetyl trimethylammonium bromide-hexanol-water system. J Colloid Interface Sci 35(2):266–27210.1016/0021-9797(71)90119-6 ↗
46. Eastoe J, Hollamby MJ, Hudson L (2006) Recent advances in nanoparticle synthesis with reversed micelles. Adv Coll Interface Sci 128–130:5–1510.1016/j.cis.2006.11.009 ↗
47. Suo QL, He WZ, Huang YC, Li CP, Hong HL, Li YX et al (2005) Micronization of the natural pigment-bixin by the SEDS process through prefilming atomization. Powder Technol 154(2–3):110–11510.1016/j.powtec.2005.05.001 ↗
48. Kang Y, Yin G, Ouyang P, Huang Z, Yao Y, Liao X et al (2008) Preparation of PLLA/PLGA microparticles using solution enhanced dispersion by supercritical fluids (SEDS). J Colloid Interface Sci 322(1):87–9410.1016/j.jcis.2008.02.031 ↗
49. Wongpinyochit T, Totten JD, Johnston BF, Seib FP (2019) Microfluidic-assisted silk nanoparticle tuning. Nanoscale Advances 1(2):873–88310.1039/C8NA00208H ↗
50. Rezaei F, Damoogh S, Reis RL, Kundu SC, Mottaghitalab F, Farokhi M (2020) Dual drug delivery system based on pH-sensitive silk fibroin/alginate nanoparticles entrapped in PNIPAM hydrogel for treating severe infected burn wound. Biofabrication 13(1):01500510.1088/1758-5090/abbb82 ↗
51. Opálková Šišková A, Kozma E, Opálek A, Kroneková Z, Kleinová A, Nagy Š et al (2020) Diclofenac embedded in silk fibroin fibers as a drug delivery system. Materials 13(16):358010.3390/ma13163580 ↗
52. Yang W, Xu H, Lan Y, Zhu Q, Liu Y, Huang S et al (2019) Preparation and characterisation of a novel silk fibroin/hyaluronic acid/sodium alginate scaffold for skin repair. Int J Biol Macromol 130:58–6710.1016/j.ijbiomac.2019.02.120 ↗
53. Brito-Pereira R, Correia DM, Ribeiro C, Francesko A, Etxebarria I, Pérez-Álvarez L et al (2018) Silk fibroin-magnetic hybrid composite electrospun fibers for tissue engineering applications. Compos B Eng 141:70–7510.1016/j.compositesb.2017.12.046 ↗
54. Mwangi TK, Bowles RD, Tainter DM, Bell RD, Kaplan DL, Setton LA (2015) Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery. Int J Pharm 485(1–2):7–1410.1016/j.ijpharm.2015.02.059 ↗
55. Dong Y, Dong P, Huang D, Mei L, Xia Y, Wang Z et al (2015) Fabrication and characterization of silk fibroin-coated liposomes for ocular drug delivery. Eur J Pharm Biopharm 91:82–9010.1016/j.ejpb.2015.01.018 ↗
56. Tallian C, Herrero-Rollett A, Stadler K, Vielnascher R, Wieland K, Weihs AM et al (2018) Structural insights into pH-responsive drug release of self-assembling human serum albumin-silk fibroin nanocapsules. Eur J Pharm Biopharm 133:176–18710.1016/j.ejpb.2018.10.002 ↗
57. Crivelli B, Bari E, Perteghella S, Catenacci L, Sorrenti M, Mocchi M et al (2019) Silk fibroin nanoparticles for celecoxib and curcumin delivery: ROS-scavenging and anti-inflammatory activities in an in vitro model of osteoarthritis. Eur J Pharm Biopharm 137:37–4510.1016/j.ejpb.2019.02.008 ↗
58. Liu C, Lin L, Huang Z, Wu Q, Jiang J, Lv L et al (2019) Novel inhalable ciprofloxacin dry powders for bronchiectasis therapy: mannitol–silk fibroin binary microparticles with high-payload and improved aerosolized properties. AAPS PharmSciTech 20(2):8510.1208/s12249-019-1291-5 ↗
59. Blasioli DJ, Kahn BT, Delisle SM, Bendele AM, Tweed-Kent AM, Santos MR et al (2017) Analgesic and anti-inflammatory efficacy of celecoxib loaded silk fibroin hydrogels after intra-articular (IA) injection in the rat peptidoglycan polysaccharide (PGPS) model of induced joint inflammation. Osteoarthritis Cartilage 25:S428–S42910.1016/j.joca.2017.02.741 ↗
60. Giménez-Siurana A, Gómez García F, Pagan Bernabeu A, Lozano-Pérez AA, Aznar-Cervantes SD, Cenis JL et al (2020) Chemoprevention of experimental periodontitis in diabetic rats with silk fibroin nanoparticles loaded with resveratrol. Antioxidants 9(1):8510.3390/antiox9010085 ↗
61. Yao Q, Lan Q-H, Jiang X, Du C-C, Zhai Y-Y, Shen X et al (2020) Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing. Theranostics 10(25):1171910.7150/thno.47682 ↗
62. Takeuchi I, Shimamura Y, Kakami Y, Kameda T, Hattori K, Miura S et al (2019) Transdermal delivery of 40-nm silk fibroin nanoparticles. Colloids Surf, B 175:564–56810.1016/j.colsurfb.2018.12.012 ↗
63. Rahmani H, Fattahi A, Sadrjavadi K, Khaledian S, Shokoohinia Y (2019) Preparation and characterization of silk fibroin nanoparticles as a potential drug delivery system for 5-fluorouracil. Advanced pharmaceutical bulletin 9(4):60110.15171/apb.2019.069 ↗
64. Zhao Z, Chen A, Li Y, Hu J, Liu X, Li J et al (2012) Fabrication of silk fibroin nanoparticles for controlled drug delivery. J Nanopart Res 14(4):1–1010.1007/s11051-012-0736-5 ↗
65. Mottaghitalab F, Farokhi M, Shokrgozar MA, Atyabi F, Hosseinkhani H (2015) Silk fibroin nanoparticle as a novel drug delivery system. J Control Release 206:161–17610.1016/j.jconrel.2015.03.020 ↗
66. Kundu J, Chung Y-I, Kim YH, Tae G, Kundu SC (2010) Silk fibroin nanoparticles for cellular uptake and control release. Int J Pharm 388(1–2):242–25010.1016/j.ijpharm.2009.12.052 ↗
67. Wenk E, Merkle HP, Meinel L (2011) Silk fibroin as a vehicle for drug delivery applications. J Control Release 150(2):128–14110.1016/j.jconrel.2010.11.007 ↗
68. Jastrzebska K, Kucharczyk K, Florczak A, Dondajewska E, Mackiewicz A, Dams-Kozlowska H (2015) Silk as an innovative biomaterial for cancer therapy. Rep Pract Oncol Radiother 20(2):87–9810.1016/j.rpor.2014.11.010 ↗
69. Seib FP, Jones GT, Rnjak-Kovacina J, Lin Y, Kaplan DL (2013) pH-dependent anticancer drug release from silk nanoparticles. Adv Healthcare Mater 2(12):1606–161110.1002/adhm.201300034 ↗
70. Mathur AB, Gupta V (2010) Silk fibroin-derived nanoparticles for biomedical applications. Nanomedicine 5(5):807–82010.2217/nnm.10.51 ↗
71. Hoshyar N, Gray S, Han H, Bao G (2016) The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine 11(6):673–69210.2217/nnm.16.5 ↗
72. Pham DT, Tiyaboonchai W (2020) Fibroin nanoparticles: a promising drug delivery system. Drug Delivery 27(1):431–44810.1080/10717544.2020.1736208 ↗
73. Raudino A, Cambria A, Sarpietro MG, Satriano C (2000) Binding of lipid vesicles to protein-coated solid polymer surfaces: a model for cell adhesion to artificial biocompatible materials. J Colloid Interface Sci 231(1):66–7310.1006/jcis.2000.7083 ↗
74. Wang X, Kluge JA, Leisk GG, Kaplan DL (2008) Sonication-induced gelation of silk fibroin for cell encapsulation. Biomaterials 29(8):1054–106410.1016/j.biomaterials.2007.11.003 ↗
75. Kim U-J, Park J, Joo Kim H, Wada M, Kaplan DL (2005) Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. Biomaterials 26(15):2775–278510.1016/j.biomaterials.2004.07.044 ↗
76. Osaka T, Nakanishi T, Shanmugam S, Takahama S, Zhang H (2009) Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells. Colloids Surf, B 71(2):325–33010.1016/j.colsurfb.2009.03.004 ↗
77. Song W, Gregory DA, Al-Janabi H, Muthana M, Cai Z, Zhao X (2019) Magnetic-silk/polyethyleneimine core-shell nanoparticles for targeted gene delivery into human breast cancer cells. Int J Pharm 555:322–33610.1016/j.ijpharm.2018.11.030 ↗
78. Numata K, Reagan MR, Goldstein RH, Rosenblatt M, Kaplan DL (2011) Spider silk-based gene carriers for tumor cell-specific delivery. Bioconjug Chem 22(8):1605–161010.1021/bc200170u ↗
79. Numata K, Mieszawska-Czajkowska AJ, Kvenvold LA, Kaplan DL (2012) Silk-based nanocomplexes with tumor-homing peptides for tumor-specific gene delivery. Macromol Biosci 12(1):75–8210.1002/mabi.201100274 ↗
80. Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E (2002) A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc Natl Acad Sci 99(11):7444–744910.1073/pnas.062189599 ↗
81. Richard JP, Melikov K, Vives E, Ramos C, Verbeure B, Gait MJ et al (2003) Cell-penetrating peptides: a reevaluation of the mechanism of cellular uptake. J Biol Chem 278(1):585–59010.1074/jbc.M209548200 ↗
82. Holm T, Johansson H, Lundberg P, Pooga M, Lindgren M, Langel Ü (2006) Studying the uptake of cell-penetrating peptides. Nat Protoc 1(2):1001–100510.1038/nprot.2006.174 ↗
83. Gupta V, Aseh A, Ríos CN, Aggarwal BB, Mathur AB (2009) Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy. Int J Nanomed 4:11510.2147/IJN.S5581 ↗
84. Li H, Tian J, Wu A, Wang J, Ge C, Sun Z (2016) Self-assembled silk fibroin nanoparticles loaded with binary drugs in the treatment of breast carcinoma. Int J Nanomed 11:437310.2147/IJN.S108633 ↗
85. Mulik RS, Mönkkönen J, Juvonen RO, Mahadik KR, Paradkar AR (2010) Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis. Int J Pharm 398(1–2):190–20310.1016/j.ijpharm.2010.07.021 ↗
86. Palit S, Kar S, Sharma G, Das PK (2015) Hesperetin Induces apoptosis in breast carcinoma by triggering accumulation of ROS and activation of ASK1/JNK pathway: breast cancer cell apoptosis by hesperetin. J Cell Physiol 230(8):1729–173910.1002/jcp.24818 ↗
87. Kakar SS, Jala VR, Fong MY (2012) Synergistic cytotoxic action of cisplatin and withaferin A on ovarian cancer cell lines. Biochem Biophys Res Commun 423(4):819–82510.1016/j.bbrc.2012.06.047 ↗
88. El-Awady E-SE, Moustafa YM, Abo-Elmatty DM, Radwan A (2011) Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. Eur J Pharmacol 650(1):335–4110.1016/j.ejphar.2010.09.085 ↗
89. Kim J-H, Kim Y-S, Park K, Lee S, Nam HY, Min KH et al (2008) Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice. J Control Release 127(1):41–4910.1016/j.jconrel.2007.12.014 ↗
90. Ding D, Zhu Z, Liu Q, Wang J, Hu Y, Jiang X et al (2011) Cisplatin-loaded gelatin-poly(acrylic acid) nanoparticles: Synthesis, antitumor efficiency in vivo and penetration in tumors. Eur J Pharm Biopharm 79(1):142–14910.1016/j.ejpb.2011.01.008 ↗
91. Li M-Y, Zhao Y, Tong T, Hou X-H, Fang B-S, Wu S-Q et al (2013) Study of the degradation mechanism of Chinese historic silk (Bombyx mori) for the purpose of conservation. Polym Degrad Stab 98(3):727–73510.1016/j.polymdegradstab.2012.12.021 ↗
92. Yang M-H, Chung T-W, Lu Y-S, Chen Y-L, Tsai W-C, Jong S-B et al (2015) Activation of the ubiquitin proteasome pathway by silk fibroin modified chitosan nanoparticles in hepatic cancer cells. IJMS 16(1):1657–167610.3390/ijms16011657 ↗
93. Chi N-H, Yang M-C, Chung T-W, Chou N-K, Wang S-S (2013) Cardiac repair using chitosan-hyaluronan/silk fibroin patches in a rat heart model with myocardial infarction. Carbohyd Polym 92(1):591–59710.1016/j.carbpol.2012.09.012 ↗
94. Omenetto FG, Kaplan DL (2010) New opportunities for an ancient material. Science 329(5991):528–53110.1126/science.1188936 ↗
95. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–143710.1038/nm.3394 ↗
96. Danhier F, Feron O, Préat V (2010) To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148(2):135–14610.1016/j.jconrel.2010.08.027 ↗
97. Cao Y, Gu Y, Ma H, Bai J, Liu L, Zhao P et al (2010) Self-assembled nanoparticle drug delivery systems from galactosylated polysaccharide–doxorubicin conjugate loaded doxorubicin. Int J Biol Macromol 46(2):245–24910.1016/j.ijbiomac.2009.11.008 ↗
98. Subia B, Chandra S, Talukdar S, Kundu SC (2014) Folate conjugated silk fibroin nanocarriers for targeted drug delivery. Integr Biol 6(2):203–21410.1039/C3IB40184G ↗
99. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discovery 4(2):145–16010.1038/nrd1632 ↗
100. Zhang Y, Hong H, Myklejord DV, Cai W (2011) Molecular imaging with SERS-active nanoparticles. Small 7(23):3261–326910.1002/smll.201100597 ↗