經基因重組大腸桿菌所生產的多精胺酸聚天門冬胺酸(multi-L-arginyl-poly-L-aspartate, MAPA) ，也稱作藍藻蛋白 (cyanophycin granule polypeptide, CGP) 。其主鏈為天門冬胺酸 (aspartic acid, Asp)，側鏈由精胺酸 (arginine, Arg) 與離胺酸 (lysine, Lys) 所組成，是一種非核糖體合成的蛋白質。有良好的生物相容性，且為具酸鹼應答特性與高臨界溶解溫度 (upper critical solution temperature, UCST) 溫敏性的智能高分子。
本研究利用順鉑與水溶性及非水溶性多精胺酸-聚天門冬胺酸以不同比例進行反應，接枝物分別命名為sMAPA-CDDP與iMAPA-CDDP。同時利用順鉑先與同樣具有良好生物相容性與標靶性的兩種分子量的透明質酸反應，再與非水溶性多精胺酸-聚天門冬胺酸利用Schiff's base formation反應機制進行交聯反應，產物命名為iMAPA-HA-CDDP。本研究探討上述接枝物的順鉑負載量，之後在模擬不同的胞內環境下進行藥物釋放測試。在細胞實驗利用黑色素腫瘤細胞B16-F10與具有順鉑抗藥性的ES-2細胞，測試接枝物對兩種細胞的毒殺能力，並且量測進入細胞內的順鉑含量。

Multi-L-arginyl-poly-L-aspartate (MAPA), also known as cyanophycin, produced by recombinant Escherichia coli contains a backbone of poly-aspartate with arginine and lysine as the side chains. It is a polypeptide of good biocompatibility.
In this study, cisplatin was reacted with soluble and insoluble MAPA at different proportions, denoted as sMAPA-CDDP and iMAPA-CDDP, respectively. Cisplatin was also reacted with two different molecular weights of hyaluronic acid which have good biocompatibility and tumor-targeted property, and then crosslinked with insoluble MAPA by Schiff’s base formation. The product was denoted as iMAPA-HA-CDDP.
The loading amount of cisplatin of each conjugate was assessed, and drug release was performed under the conditions that simulated different intracellular environments. Melanoma tumor cells, B16-F10 and ES-2 cells of cisplatin resistance, were used to examine the cytotoxicity of the conjugates, and the intracellular amounts of cisplatin were measured.
Using MAPA as a carrier of cisplatin can help the drug enter the cells through endocytosis, and achieve better cytotoxic effect than free cisplatin. The results showed that MAPA can be a potential drug carrier of cisplatin.

1. F. Oppermann-Sanio, & Alexander Steinbüchel. Occurrence, functions and biosynthesis of polyamides in microorganisms and biotechnological production. Naturwissenschaften, 2002. 89(1): p. 11-22.
2. Robert D. Simon. Cyanophycin granules from the blue-green alga anabaena cylindrica: a reserve material consisting of copolymers of aspartic acid and arginine. Proceedings of the National Academy of Sciences, 1971. 68(2): p. 265-267.
3. Robert D. Simon, & Pamela Weathers. Determination of the structure of the novel polypeptide containing aspartic acid and arginine which is found in cyanobacteria. Biochimica et Biophysica Acta (BBA), 1976. 420(1): p. 165-176.
4. Elsayed Aboulmagd, Ingo Voss, Fred B. Oppermann-Sanio, & Alexander Steinbu1 chel. Heterologous expression of cyanophycin synthetase and cyanophycin synthesis in the industrial relevant bacteria Corynebacterium glutamicum and Ralstonia eutropha and in Pseudomonas putida. Biomacromolecules, 2001. 2(4): p. 1338-1342.
5. Karl Ziegler, Annette Diener, Carine Herpin, Ralf Richter, Rainer Deutzmann, & Wolfgang Lockau. Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi‐L‐arginyl‐poly‐L‐aspartate (cyanophycin). European Journal of Biochemistry, 1998. 254(1): p. 154-159.
6. Anna Steinle, Klaus Bergander, & Alexander Steinbu¨chel1. Metabolic engineering of saccharomyces cerevisiae for production of novel cyanophycins with an extended range of constituent amino acids. Applied and Environmental Microbiology, 2009. 75(11): p. 3437-3446.
7. Jens Kroll, Stefan Klinter, & Alexander Steinbüchel. A novel plasmid addiction system for large-scale production of cyanophycin in Escherichia coli using mineral salts medium. Applied Microbiology and Biotechnology, 2011. 89(3): p. 593-604.
8. W. C. Tseng, T. Y. Fang, C. Y. Cho, P. S. Chen, & C. S. Tsai. Assessments of growth conditions on the production of cyanophycin by recombinant Escherichia coli strains expressing cyanophycin synthetase gene. Biotechnology Progress, 2012. 28(2): p. 358-363.
9. Holger Berg, Karl Ziegler, Kirill Piotukh, Kerstin Baier, Wolfgang Lockau, & Rudolf Volkmer-Engert. Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin). European Journal of Biochemistry, 2000. 267(17): p. 5561-5570.
10. W. C. Tseng, T. Y. Fang, Y. C. Hsieh, C. Y. Chen, & M. C. Li. Solubility and thermal response of fractionated cyanophycin prepared with recombinant Escherichia coli. Journal of Biotechnology, 2017. 249: p. 59-65.
11. Daniel K.Y. Solaiman, Rafael A. Garcia, Richard D. Ashby, George J. Piazza, & Alexander Steinbüchel. Rendered-protein hydrolysates for microbial synthesis of cyanophycin biopolymer. New Biotechnology, 2011. 28(6): p. 552-558.
12. Bas J. Meussen, Ruud A. Weusthuis, Johan P. M. Sanders, & Leo H. de Graaff. Production of cyanophycin in Rhizopus oryzaethrough the expression of a cyanophycin synthetase encoding gene. Applied Microbiology and Biotechnology, 2012. 93(3): p. 1167-1174.
13. A. Sallam, & A. Steinbüchel. Cyanophycin-degrading bacteria in digestive tracts of mammals, birds and fish and consequences for possible applications of cyanophycin and its dipeptides in nutrition and therapy. Journal of Applied Microbiology, 2009. 107(2): p. 474-484.
14. Elinor Scott, Francisc Peter, & Johan Sanders. Biomass in the manufacture of industrial products—the use of proteins and amino acids. Applied Microbiology and Biotechnology, 2007. 75(4): p. 751-762.
15. A. Sallam, A. Kast, S. Przybilla, T. Meiswinkel, & A. Steinbüchel. Biotechnologicl process for production of β-dipeptides from cyanophycin on a technical scale and its optimization. Applied and Environmental Microbiology, 2008. 75(1): p. 29-38.
16. A. Sallam, & A. Steinbüchel. Cyanophycin-degrading bacteria in digestive tracts of mammals birds and fish and consequences for possible applications of cyanophycin and its dipeptides in nutrition and therapy. Journal of Applied Microbiology, 2009. 107(2): p. 474-484.
17. Karl Meyer, & John W. Palmer. The polysacchride of the vitrious humor. Journal of Biological Chemistry, 1934. 107(3): p. 629-634.
18. E. D. T. Atkins, & J. K. Sheehan. Structure for hyaluronic acid. Nature New Biology, 1972. 235(1): p. 253-254.
19. P. Saranraj, & M. A. Naidu. Hyaluronic acid production and its applications - a review. International Journal of Pharmaceutical & Biological Archives, 2013. 4(5): p. 853-859.
20. Forrest E. Kendall, Michael Heidelberger, & Martin H. Dawson. A Serologically inactive polysaccharide elaborated by mucoid strains of group a hemolytic streptococcus. Journal of Biological Chemistry, 1937. 118(1): p. 61-69.
21. Valarie L. Tlapak-Simmons, Bruce A. Baggenstoss, Tracy Clyne, & Paul H. Weigel. Purification and lipid dependence of the recombinant hyaluronan synthases from streptococcus pyogenes and streptococcus equisimilis. Journal of Biological Chemistry, 1999. 274(7): p. 4239-4245.
22. David C. Armstrong, & Michael R. Johns. Culture conditions affect the molecular weight properties of hyaluronic acid produced by streptococcus zooepidemicus. Applied and Environmental Microbiology, 1997. 63(7): p. 2759-2764.
23. Mark van Beek, Andrea Weeks, Lyndon Jones, & Heather Sheardown. Immobilized hyaluronic acid containing model silicone hydrogels reduce protein adsorption. Journal of Biomaterials Science, Polymer Edition, 2008. 19(11): p. 1425–1436.
24. Cortivo R., De Galateo A., Castellani I., Brun P., Giro M. G., & Abatangelo G.. Hyaluronic acid promotes chick embryo fibroblast and chondroblast expression. Cell Biology International Reports, 1990. 14(2): p. 111-122.
25. Pierre Andre. New trends in face rejuvenation by hyaluronic acid injections. Journal of Cosmetic Dermatology, 2008. 7(4): p. 251-258.
26. Suhail K. Kanchwala, Lisa Holloway, & Louis P. Bucky. Reliable soft tissue augmentation. Annals of Plastic Surgery, 2005. 55(1): p. 30-35.
27. Ahmet Tezel, & Glenn H. Fredrickson. The science of hyaluronic acid dermal fillers. Journal of Cosmetic and Laser Therapy, 2008. 10(1): p. 35-42.
28. Dmitri A Ossipov. Nanostructured hyaluronic acid-based materials for active delivery to cancer. Expert Opinion on Drug Delivery, 2010. 7(6): p. 681-703.
29. L. Wang, & E. Jia. Ovarian cancer targeted hyaluronic acid-based nanoparticle system for paclitaxel delivery to overcome drug resistance. Drug Delivery, 2016. 23(5): p. 1810-1817.
30. Enrique Lallana, Julio Rios De La Rosa, Annalisa Tirella, Maria Pelliccia, Arianna Gennari, Ian Stratford, Sanyogitta Puri, Marianne Ashford, & Nicola Tirelli. Chitosan/hyaluronic acid nanoparticles: rational design revisited for RNA delivery. Molecular Pharmaceutics, 2017. 14(7): p. 2422-2436.
31. T. Lin, A. Yuan, X. Zhao, H. Lian, J. Zhuang, W. Chen, Q. Zhang, G. Liu, S. Zhang, W. Chen, W. Cao, C. Zhang, J. Wu, Y. Hu, & H. Guo. Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer. Acta Biomaterialia 2017. 53(15): p. 427-438.
32. Naila El Kechai, Elisabeth Mamelle, Yann Nguyen, Nicolas Huang, Val´erie Nicolas, Pierre Chaminade, St´ephanie Yen-Nicola¨y, Claire Gueutin, Benjamin Granger, Evelyne Ferrary, Florence Agnely, & Am´elie Bochot. Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear. Journal of Controlled Release, 2016. 226(1): p. 248-257.
33. S. E. Han, H. Kang, G. Y. Shim, S. J. Kim, H. G. Choi, J. Kim, S. K. Hahn, & Y. K. Oh. Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides. Journal of Drug Targeting, 2009. 17(2): p. 123-132.
34. S. H. Wang, M. J. Cao, X. W. Deng, X. Q. Xiao, Z. X. Yin, Q. Hu, Z. X. Zhou, F. Zhang, R. R. Zhang, Y. Wu, W. Sheng, & Y. Zeng. Degradable hyaluronic acid/protamine sulfate interpolyelectrolyte complexes as miRNA-delivery nanocapsules for triple-negative breast cancer therapy. Advanced Healthcare Materials, 2015. 4(2): p. 281-290.
35. G. Wu, L. Chen, H. Li, & Y. J. Wang. Hyaluronic acid as an internal phase additive to obtain ofloxacin/PLGA microsphere by double emulsion method. Bio-Medical Materials and Engineering, 2014. 24(1): p. 751-756.
36. X. Y. Yang, Y. X. Li, M. Li, L. Zhang, L. X. Feng, & N. Zhang. Hyaluronic acid-coated nanostructured lipid carriers for targeting paclitaxel to cancer. Cancer Letters, 2013. 334(2): p. 338-345.
37. J. Yao, Y. Fan, R. H. Du, J. P. Zhou, Y. Lu, W. Wang, J. Ren, & X. J. Sun. Amphoteric hyaluronic acid derivative for targeting gene delivery. Biomaterials, 2010. 31(35): p. 9357-9365.
38. X. H. Fan, X. S. Zhao, X. K. Qu, & J. Fang. pH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivoantitumor effect. International Journal of Pharmaceutics, 2015. 496(2): p. 644-653.
39. Chad E. Galer, Daisuke Sano, Sukhen C. Ghosh, Jeong H. Hah, Edmund Auzenne, Amirali N. Hamir, Jeffrey N. Myers, & Jim Klostergaard. Hyaluronic acid–paclitaxel conjugate inhibits growth of human squamous cell carcinomas of the head and neck via a hyaluronic acid-mediated mechanism. Oral Oncology, 2011. 47(11): p.1039-1047.
40. E. L. Liu, Y. X. Zhou, Z. Liu, J. Li, D. H. Zhang, J. C. Chen, & Z. H. Cai. Cisplatin loaded hyaluronic acid modified TiO2 nanoparticles for neoadjuvant chemotherapy of ovarian cancer. Journal of Nanomaterials, 2015. 16(1): p. 275.
41. A. Jong, C. H. Wu, I. Gonzales Gomez, K. J. Kwon Chung, Y. C. Chang, H. K. Tseng, W. L. Cho, & S. H. Huang. Hyaluronic acid receptor CD44 deficiency is associated with decreased cryptococcus neoformans brain infection. Journal of Biological Chemistry, 2012. 287(19): p. 15298-15306.
42. Warren Knudson, Geraldine Chow, & Cheryl B Knudson. CD44-mediated uptake and degradation of hyaluronan. Matrix Biology, 2002. 21(1): p. 15-23.
43. E. López-Ruiz, G. Jiménez, L. Álvarez de Cienfuegos, C. Antich, R. Sabata, J.A. Marchal, & P. Gálvez-Martín. Advances of hyaluronic acid in stem cell therapy and tissue engineering, including current clinical trials. European Cells and Materials, 2019. 37(1): p. 186-213.
44. Bo Chen, Robert J. Miller, & Pradeep K. Dhal. Hyaluronic acid-based drug conjugates: state-of-the-art and perspectives. Journal of Biomedical Nanotechnology, 2014. 10(1): p. 4-16.
45. Pieter T. Bot, Imo E. Hoefer, Jan J. Piek, & Gerard Pasterkamp. Hyaluronic acid: targeting immune modulatory components of the extracellular matrix in atherosclerosis. Current Medicinal Chemistry, 2008. 15(8): p. 786-791.
46. Vanessa T. Chivere, Pierre P. D. Kondiah, Yahya E. Choonara, & Viness Pillay. Nanotechnology-based biopolymeric oral delivery platforms for advanced cancer treatment. Cancers 2020. 12(2): p. 522.
47. A. M. Creighton, K. Hellmann, & Susan Whitecross. Antitumour activity in a series of bisDiketopiperazines. Nature, 1969. 222(1): p. 384-385.
48. Hien T. T. Duong, Vien T. Huynh, Paul de Souza, & Martina H. Stenzel. Core-cross-linked micelles synthesized by clicking bifunctional Pt(IV) anticancer drugs to isocyanates. Biomacromolecules, 2010. 11(9): p. 2290-2299.
49. Hardeep S. Oberoi, Natalia V. Nukolova, Alexander V. Kabanov, & Tatiana K. Bronich. Nanocarriers for delivery of platinum anticancer drugs. Advanced Drug Delivery Reviews, 2013. 65(13-14): p. 1667-1685.
50. Caro Schaake-Koning, Walter Van Den Bogaert, Otilia Dalesio, Jan Festen, Jaap Hoogenhout, Paul Van Houtte, Anne Kirkpatrick, Mia Koolen, Ben Maat, Arie Nijs, Alain Renaud, Patrick Rodrigus, Lon Schuster-Uitterhoeve, Jean-Paul Sculier, Nico Van Zandwijk, & Harry Bartelink. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. The New England Journal Of Medicine, 1992. 326(1): p. 524-530.
51. Renata Žaludová, Alena Žákovská, Jana Kašpárková, Zdenka Balcarová, Vladimír Kleinwächter, Oldřich Vrana, Nicholas Farrell, & Viktor Brabec. DNA interactions of bifunctional dinuclear platinum(II) antitumor agents. Eur. J. Biochem., 1997. 246(2): p. 508-517.
52. Bernhard Lippert. Impact of Cisplatin on the recent development of Pt coordination chemistry: a case study. Coordination Chemistry Reviews, 1999. 182(1): p. 263-295.
53. Irena Kostova. Platinum complexes as anticancer agents. Recent Patents on Anti-Cancer Drug Discovery, 2006. 1(1): p. 1-22.
54. Roger Y. Tsang, Turki Al-Fayea, & Dr Heather-Jane Au. Cisplatin overdose. Drug safety, 2009. 32(12): p. 1109–1122.
55. Ana-Maria Florea, & Dietrich Büsselberg. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers, 2011. 3(4): p. 1351-1371.
56. Tomaz Makovec. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiology and Oncology, 2019. 53(2): p. 148-158.
57. Seiko Ishida, Jaekwon Lee, Dennis J. Thiele, & Ira Herskowitz. Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Biological Sciences, 2002. 99(22): p. 14298-14302.
58. Carlos R. Ferreira, & William A. Gahl. Disorders of metal metabolism. Translational Science of Rare Diseases, 2017. 2(3-4): p. 101-139.
59. Francesco Tadini-Buoninsegni, Gianluca Bartolommei, Maria Rosa Moncelli, Giuseppe Inesi, Angela Galliani, Maril Sinisi, Maurizio Losacco, Giovanni Natile, & Fabio Arnesano. Translocation of platinum anticancer drugs by human copper ATPases ATP7A and ATP7B. Angewandte Chemie, 2014. 126(5): p.1321-1325.
60. Peter C. Dedon, & Richard F. Borch. Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles. Biochemical Pharmacology, 1987. 36(12): p. 1955-1964.
61. Alan Eastman. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacology & Therapeutics, 1987. 34(2): p. 155-166.
62. Toshihisa Ishikawa, & Francis Ali-Osman. Glutathione-associated cis-Diamminedichloroplatinum(I1) metabolism and ATP-dependent efflux from leukemia Cells. Journal of Biological Chemistry, 1993. 268(27): p. 20116-20125.
63. Khalid M. El-Say, & Hossam S. El-Sawy. Polymeric nanoparticles: promising platform for drug delivery. International Journal of Pharmaceutics, 2017. 528(1-2): p. 675-691.
64. Noor Alam, Mytre Koul, Mubashir J. Mintoo, Vaibhav Khare, Rahul Gupta, Neha Rawat, Parduman Raj Sharma, Shashank K. Singhb, Dilip M. Mondheb, & Prem N. Gupta. Development and characterization of hyaluronic acid modified PLGA based nanoparticles for improved efficacy of cisplatin in solid tumor. Biomedicine & Pharmacotherapy, 2017. 95(1): p. 856-864.
65. H. T. Zhang, F. Li, J. Yic, C. H. Gu, L. Fan, Y. B. Qiao, Y. C. Tao, C. Cheng, & H. Wu. Folate-decorated maleilated pullulan–doxorubicin conjugate for active tumor-targeted drug delivery. European Journal of Pharmaceutical Sciences, 2011. 42(5): p. 517-526.
66. Muhammad Asim Farooq, Md Aquib, Anum Farooq, Daulat Haleem Khan, Mily Bazezy Joelle Maviah, Mensura Sied Filli, Samuel Kesse, Kofi Oti Boakye- Yiadom, Rukhshona Mavlyanova, Amna Parveen, & Bo Wang. Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview. Artificial Cells, Nanomedicine, and Biotechnology, 2019. 47(1): p. 1674-1692.
67. Mostafa Shahin, Nazila Safaei-Nikouei, & Afsaneh Lavasanifar. Polymeric micelles for pH-responsive delivery of cisplatin. Journal of Drug Targeting, 2014. 22(7): p. 629-637.
68. Y. D. Gu, Y. N. Zhong, F. H. Meng, R. Cheng, C. Deng, & Z. Y. Zhong. Acetal-linked paclitaxel prodrug micellar nanoparticles as a versatile and potent platform for cancer therapy. Biomacromolecules, 2013. 14(8): p. 2772-2780.
69. Hiroshi Maedaa, Tomohiro Sawa, & Toshimitsu Konno. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical q overview of the prototype polymeric drug SMANCS. Journal of Controlled Release, 2001. 74(1-3): p. 47-61.
70. X. Pang, Y. Jiang, Q. C. Xiao, W. N. Leung, H. Y. Hua, & C. S. Xu. pH-responsive polymer-drug conjugates: design and progress. Journal of Controlled Release, 2016. 222(28): p. 116-129.
71. Jason Mercer, & Ari Helenius. Virus entry by macropinocytosis. Nature Cell Biology, 2009. 11(1): p. 510-520.
72. Shi Xu, Bogdan Z. Olenyuk, Curtis T. Okamoto , & Sarah F. Hamm-Alvarez. Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances. Advanced Drug Delivery Reviews, 2013. 65(1): p. 121-138.
73. Harvey T. McMahon, & Emmanuel Boucrot. Molecular mechanism and physiological functions of clathrin‑mediated endocytosis. Nature Reviews Molecular Cell Biology, 2011. 12(1): p. 517-533.
74. Alexander Sorkin. Cargo recognition during clathrin-mediated endocytosis: a team effort. Current Opinion in Cell Biology, 2004. 16(4): p. 392-399.
75. Eva M. Schmid, & Harvey T. McMahon. Integrating molecular and network biology to decode endocytosis. Nature, 2007. 448(1): p. 883-888.
76. D. K. Kim, H. Y. Kim, & J. S. Koo. Expression of caveolin-1, caveolin-2 and caveolin-3 in thyroid cancer and stroma. Pathobiology, 2012. 79(1): p. 1-10.
77. Gary J. Doherty, & Harvey T. McMahon. Mechanisms of endocytosis. Annu. Rev. Biochem, 2009. 78(31): p. 31-46.
78. Kai Simons, & Derek Toomre. Lipid rafts and signal transduction. Nature Reviews Molecular Cell Biology, 2000. 1(1): p. 31-39.
79. Karen G. Rothberg, John E. Heuser, William C. Donzell, Yun-Shu Ying, John R. Glenney, & Richard G. W. Anderson. Caveolin, a protein component of caveolae membrane coats. Cell, 1992. 68(4): p. 673-682.
80. Robert G. Parton, & Ayanthi A. Richards. Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic, 2003. 4(11): p. 724-738.
81. Markus C. Kerr, & Rohan D. Teasdale. Defining macropinocytosis. Traffic, 2009. 10(4): p. 364-371.
82. Sue D. Xiang, Anja Scholzen, Gabriela Minigo, Cassandra David, Vasso Apostolopoulos, Patricia L. Mottram, & Magdalena Plebanski. Pathogen recognition and development of particulate vaccines: Does size matter?. Methods, 2006. 40(1): p. 1-9.
83. Mohit Basotra, Sachin Kumar Singh, & Monica Gulati. Development and validation of a simple and sensitive spectrometric method for estimation of cisplatin hydrochloride in tablet dosage forms: application to dissolution studies. ISRN Analytical Chemistry, 2013. 1(1): p. 1-8.
84. Karun Thongprajukaew, Aree Choodum, Barunee Sa-E, & Ummah Hayee. Smart phone: a popular device supports amylase activity assay in fisheries research. Food Chemistry, 2014. 163(1): p. 87-91.
85. Alexandre Ambrogelly, Collette Cutler, & Brittany Paporello. Screening of reducing agents for the PEGylation of recombinant human IL-10. The Protein Journal, 2013. 32(1): p. 337-342.
86. G. Tomlinson, & T. Viswanatha. Determination of the arginine content of proteins by the sakaguchi procedure. Analytical Biochemistry, 1974. 60(1): p. 15-24.
87. Mengyuan Hea, Jiarong Guoa, Jiahua Yanga, Yang Yanga, Songyan Zhaoa, Qiao Xub, Tiangxiang Weib, Davide Maria Ferrarisc, Tao Gaoa, & Zhigang Guoa. A highly selective electrochemical assay based on the Sakaguchi reaction for the detection of protein arginine methylation state. Electrochemistry Communications, 2020. 118(1): p. 106-808.
88. Zacharias Dische, & Ellen Borenfreund. A new spectrophotometric method for the detection and determination of keto sugars and trioses. J Biol Chem., 1951. 192(2): p. 583-587.
89. Ralph W. Scott, Wayne E. Moore, Marilyn J. Effland, & MerrillL A. Millett. Ultraviolet spectrophotometric determination of hexoses, pentoses, and uronic acids after their reactions with concentrated sulfuric acid. Analytical Biochemistry, 1967. 21(1): p. 68-80.
90. Syotaro Oka, Yaichiro Sibazaki, & Shu Tahara. Direct potentiometric determination of chloride ion in whole blood. Anal. Chem., 1891. 53(1): p.588-593.
91. Victor Faundez, & H. Criss Hartzell. Intracellular chloride channels: determinants of function in the endosomal pathway. Science Signaling, 2004. 2004(233): p. re8.
92. Kasturi Chakraborty, KaHo Leung, & Yamuna Krishnan. High lumenal chloride in the lysosome is critical for lysosome function. Cell Biology, 2017. 6(1): p. 1-25.
93. Stuart H. Yuspa, & David L. Morgan. Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature, 1981. 293(1): p. 72-74.
94. Masato Yoshihara, Hiroaki Kajiyama, Akira Yokoi, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Wenting Liu, Kae Nakamura, Yoshinori Moriyama, Hiroaki Yasui, Shiro Suzuki, Yusuke Yamamoto, Carmela Ricciardelli, Akihiro Nawa, Kiyosumi Shibata, & Fumitaka Kikkawa. Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway. Internatioal Jounal of Cancer, 2020. 146(8): p. 2268-2280.
95. L. P. Madhubhani P. Hemachandra, Dong-Hui Shin, Usawadee Dier, James N. Iuliano, Sarah A Engelberth, Larissa M. Uusitalo, Susan K. Murphy, & Nadine Hempel. Mitochondrial superoxide dismutase has a pro-tumorigenic role in ovarian clear cell carcinoma. Cancer Research, 2015. 75(22): p. 4973-4984.
96. Mehdi Abedi, Samira Sadat Abolmaali, Mozhgan Abedanzadeh, Sedigheh Borandeh, Soliman Mohammadi Samani, & Ali Mohammad Tamaddon. Citric acid functionalized silane coupling versus post-grafting strategy for dual pH and saline responsive delivery of cisplatin by Fe3O4/carboxyl functionalized mesoporous SiO2 hybrid nanoparticles: A-synthesis, physicochemical and biological characterization. Materials Science and Engineering: C, 2019. 104(1): p. 109-922.
97. Agnieszka Kowalczuka, Ekaterina Stoyanovab, Violeta Mitovab, Pavletta Shestakovac, Georgi Momekovd, Denitsa Momekovad, & Neli Kosevab. Star-shaped nano-conjugates of cisplatin with high drug payload. International Journal of Pharmaceutics, 2011. 404(1-2): p. 220-230.
98. Amir Fakhari, Quang Phan, & Cory J. Berkland. Hyaluronic acid nanoparticles titrate the viscoelastic properties of viscosupplements. Langmuir, 2013. 29(17): p. 5123-5131.
99. J. L. Hueso, J. P. Espino’ s, A. Caballero, J. Cotrino, & A. R. Gonza´lez-Elipe. XPS investigation of the reaction of carbon with NO, O2, N2 and H2O plasmas. Carbon, 2007. 45(1): p. 89-96.
100. L. Li, H. S. Zhang, H. Zhao, D. W. Shi, C. S. Zheng, Y. B. Zhao, & X. L. Yang. Radiofrequency-thermal effect of cisplatin-crosslinked nanogels for triple therapies of ablation-chemo-embolization. Chemical Engineering Journal, 2022. 450(4): p. 138-421.
101. J. L. Gu, J. P. Liu, Y. S. Li, W. R. Zhao, & J. L. Shi. One-pot synthesis of mesoporous silica nanocarriers with tunable particle sizes and pendent carboxylic groups for cisplatin delivery. Langmuir, 2013. 29(1): p. 403-410.
102. E. L. Liu, Y. X. Zhou, Z. Liu, J. Li, D. H. Zhang, J. C. Chen, & Z. H. Cai. Cisplatin loaded hyaluronic acid modified TiO2 nanoparticles for neoadjuvant chemotherapy of ovarian cancer. Journal of Nanomaterials, 2015. 16(1): p. 275.