癌症是一種毀滅性的疾病，死亡率逐年增加，是全世界人類健康面臨的挑戰之一。常見的治療方式，包括化療和放療，而全身化療的關鍵問題是藥物的非特異性分佈，造成健康細胞的損傷。薑黃素具有抗氧化、抗發炎、抑制微生物生長和抗癌的特性，但其易受光照而裂解且水溶性差導致不易吸收，限制生物利用度而降低其治療成效，因此在臨床應用受到限制。本研究中添加 Pluronic 提升薑黃素的溶解度，再以幾丁聚醣 (Chitosan, C) 與石蓴多醣 (Ulvan, U) 製備成奈米粒，並透過不同重量比篩選出符合癌症治療之 pH 變化的奈米粒，並藉由石蓴多醣含有大量的鼠李醣，可與具有鼠李醣結合凝集素 (Rhamnose Binding Lectin, RBL) 受體的癌細胞進行特異性結合，達到藥物標靶遞送及 pH 敏感釋放。本實驗成功製備出具 pH 敏感性的薑黃素-PF 127/石蓴多醣-幾丁聚醣奈米粒，薑黃素、PF127、石蓴多醣、幾丁聚醣重量比為 0.6：0.2：4.0:1.0 (Cur-PF/U4C1 NPs)，粒徑為 200.80±7.35 nm，Zeta 電位為 -25.93±2.04 mV，薑黃素包覆率 (Encapsulation Efficiency, EE)為 78.22±3.65%、藥物裝載率 (Loading Content, LC) 為 8.09±0.38%。Cur-PF/U4C1 奈米粒於癌症內部微環境 (pH 5.0 及 6.0) 崩解，利於藥物釋放，而在生理條件及癌症外部微環境 (pH 7.4 及 6.8) 時，奈米粒呈球型且穩定存在，有利於藥物標靶遞送癌細胞。體外釋放研究表明薑黃素奈米粒在酸性條件爆發釋放，一般生理環境緩慢釋放。細胞實驗中，Cur-PF/U4C1 奈米粒與 A431 和 PC3 細胞 RBL receptor 特異性結合，達到藥物標靶遞送，因此可以在短時間、低濃度即產生明顯的細胞毒性，並觀察到石蓴多醣和薑黃素在 B16F10 細胞的加乘抗癌效果。綜上所述，薑黃素-PF 127/石蓴多醣-幾丁聚醣奈米粒 (Cur-PF/U4C1 NPs) 穩定存在且具有 pH 敏感特性，有利於藥物在癌症腫瘤細胞 pH 敏感釋放，並且可與具有 RBL receptor 的癌細胞進行特異性結合，達到藥物標靶遞送，避免造成健康細胞損傷且有助於提升抗癌能力。

Cancer is a devastating disease with an increasing mortality rate year by year, which is one of the challenges facing human health all over the world. Common treatment modalities include chemotherapy and radiotherapy, while a key problem with systemic chemotherapy is the non-specific distribution of the drug, causing damage to healthy cells. Curcumin has anti-oxidative, anti-inflammatory, microbial growth inhibition and anti-cancer properties, but it is easily decomposed by light, and its poor water solubility makes it difficult to absorb, which limits its bioavailability and reduces its therapeutic efficacy, so its clinical application is limited. In this study, Pluronic was added to improve the solubility of curcumin, and then chitosan (C) and Ulvan (U) were used to prepare nanoparticles, and the pH changes in line with cancer treatment were screened through different weight ratios. Ulvan contains a large amount of rhamnose, it can specifically bind to cancer cells with Rhamnose Binding Lectin (RBL) receptors to achieve drug target delivery and pH-sensitive release. In this experiment, pH-sensitive curcumin-PF 127/Ulvan-chitosan nanoparticles were successfully prepared. The weight ratio of curcumin, PF127, Ulvan and chitosan was 0.6:0.2:4.0:1.0 (Cur-PF/U4C1 NPs), particle size is 200.80±7.35 nm, Zeta potential is -25.93±2.04 mV, curcumin encapsulation efficiency (EE) is 78.22±3.65%, drug loading content (LC) was 8.09±0.38%. The Cur-PF/U4C1 NPs disintegrated in the cancer internal microenvironment (pH 5.0 and 6.0), which facilitated drug release, while the NPs were spherical and stable under physiological conditions and in the cancer external microenvironment (pH 7.4 and 6.8), which is beneficial for drug target delivery to cancer cells. In vitro release studies have shown that curcumin nanoparticles are burst-released in acidic conditions and slowly released in physiological environments. In cell experiments, Cur-PF/U4C1 nanoparticles specifically bind to RBL receptors on A431 and PC3 cells to achieve drug target delivery, so it can produce obvious cytotoxicity in a short time and low concentration, and observed that Ulvan and curcumin in B16F10 cells multiplied the anticancer effect. In conclusion, curcumin-PF 127/Ulvan-Chitosan nanoparticles (Cur-PF/U4C1 NPs) is stable and has pH-sensitive properties, which is beneficial to the pH-sensitive release of drugs in cancer tumor cells, and can be combined with cancer cell with RBL receptors specifically bind to target drug delivery, avoid damage to healthy cells and help improve cancer resistance.

摘要 iv
目錄 vi
圖目錄 vii
表目錄 ix
第一章、 前言 1
第二章、 文獻回顧 2
2.1 癌症 2
2.2薑黃素 5
2.3 奈米技術 7
2.4 石蓴多醣 8
第三章、 實驗動機與目的 10
第四章、 實驗流程 11
第五章、 實驗材料與方法 12
5.1實驗材料 12
5.2實驗藥品 12
5.3實驗儀器 13
5.4實驗溶液配製 15
5.5實驗方法 16
第六章、 結果與討論 24
6.1 石蓴多醣/幾丁聚醣奈米粒之物理化學特性 24
6.2 薑黃素-PF 127 /石蓴多醣-幾丁聚醣奈米粒之物理化學特性 30
6.3 奈米粒中間機制探討 36
6.4 儲存穩定性測試 42
6.5 pH 值敏感釋放 44
6.6 細胞實驗 47
第七章、 結論 63
第八章、 參考文獻 64
第九章、 附錄 73

Acharya, S., & Sahoo, S. K. (2011). PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Advanced Drug Delivery Reviews, 63(3), 170-183.
Aggarwal, B. B., & Harikumar, K. B. (2009). Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The international Journal of Biochemistry & Cell Biology, 41(1), 40-59.
Anand, P., Kunnumakara, A. B., Sundaram, C., Harikumar, K. B., Tharakan, S. T., Lai, O. S., Sung, B., & Aggarwal, B. B. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research, 25(9), 2097-2116.
Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics, 4(6), 807-818.
Anitha, A., Maya, S., Deepa, N., Chennazhi, K., Nair, S., Tamura, H., & Jayakumar, R. (2011). Efficient water soluble O-carboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells. Carbohydrate Polymers, 83(2), 452-461.
Ayala, V., Herrera, A. P., Latorre-Esteves, M., Torres-Lugo, M., & Rinaldi, C. (2013). Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles. Journal of Nanoparticle Research, 15(8), 1874.
Azandaryani, A. H., Kashanian, S., Shahlaei, M., Derakhshandeh, K., Motiei, M., & Moradi, S. (2019). A comprehensive physicochemical, in vitro and molecular characterization of letrozole incorporated chitosan-lipid nanocomplex. Pharmaceutical Research, 36(4), 1-11.
Bae, Y. M., Park, Y. I., Nam, S. H., Kim, J. H., Lee, K., Kim, H. M., Yoo, B., Choi, J. S., Lee, K. T., Hyeon, T., & Suh, Y. D. (2012). Endocytosis, intracellular transport, and exocytosis of lanthanide-doped upconverting nanoparticles in single living cells. Biomaterials, 33(35), 9080-9086.
Baliga, M. S., Joseph, N., Venkataranganna, M. V., Saxena, A., Ponemone, V., & Fayad, R. (2012). Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations. Food & Function, 3(11), 1109-1117.
Batrakova, E. V., & Kabanov, A. V. (2008). Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. Journal of Controlled Release, 130(2), 98-106.
Benltoufa, S., Miled, W., Trad, M., Slama, R. B., & Fayala, F. (2020). Chitosan hydrogel‐coated cellulosic fabric for medical end-use: Antibacterial properties, basic mechanical and comfort properties. Carbohydrate Polymers, 227, 115352.
Bibi, N., ur Rehman, A., Rana, N. F., Akhtar, H., Khan, M. I., Faheem, M., Jamal, S. B., & Ahmed, N. (2022). Formulation and characterization of curcumin nanoparticles for skin cancer treatment. Applied Nanoscience.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424.
Cheng, X., Hu, T., Li, C., Shi, S., Xu, Y., Jia, C., & Tang, R. (2021). Acid-sensitive and L61-crosslinked hyaluronic acid nanogels for overcoming tumor drug-resistance. International journal of biological macromolecules, 188, 11-23.
Dantas Lopes Dos Santos, D., Besegato, J. F., de Melo, P. B. G., Oshiro Junior, J. A., Chorilli, M., Deng, D., Bagnato, V. S., & Rastelli, A. N. d. S. (2021). Curcumin-loaded Pluronic F-127 Micelles as a Drug Delivery System for Curcumin-mediated Photodynamic Therapy for Oral Application. Photochemistry and Photobiology, 97(5), 1072-1088.
Das, R. K., Kasoju, N., & Bora, U. (2010). Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine, 6(1), 153-160.
Devassy, J. G., Nwachukwu, I. D., & Jones, P. J. (2015). Curcumin and cancer: barriers to obtaining a health claim. Nutrition Reviews, 73(3), 155-165.
Di Donato, C., Iacovino, R., Isernia, C., Malgieri, G., Varela-Garcia, A., Concheiro, A., & Alvarez-Lorenzo, C. (2020). Polypseudorotaxanes of Pluronic® F127 with Combinations of α-and β-Cyclodextrins for Topical Formulation of Acyclovir. Nanomaterials, 10(4), 613.
Don, T.-M., Liu, L.-M., Chen, M., & Huang, Y.-C. (2021). Crosslinked complex films based on chitosan and ulvan with antioxidant and whitening activities. Algal Research, 58, 102423.
Farokhzad, O. C., & Langer, R. (2009). Impact of nanotechnology on drug delivery. ACS Nano, 3(1), 16-20.
Faury, G., Ruszova, E., Molinari, J., Mariko, B., Raveaud, S., Velebny, V., & Robert, L. (2008). The α-l-Rhamnose recognizing lectin site of human dermal fibroblasts functions as a signal transducer: Modulation of Ca2+ fluxes and gene expression. Biochimica et Biophysica Acta (BBA)-General Subjects, 1780(12), 1388-1394.
Fernández-Díaz, C., Coste, O., & Malta, E.-j. (2017). Polymer chitosan nanoparticles functionalized with Ulva ohnoi extracts boost in vitro ulvan immunostimulant effect in Solea senegalensis macrophages. Algal Research, 26, 135-142.
Figueira, T. A., da Silva, A. J. R., Enrich-Prast, A., Yoneshigue-Valentin, Y., & de Oliveira, V. P. (2020). Structural characterization of ulvan polysaccharide from cultivated and collected Ulva fasciata (Chlorophyta). Advances in Bioscience and Biotechnology, 11(5), 206-216.
Fox, L. T., Gerber, M., Plessis, J. D., & Hamman, J. H. (2011). Transdermal Drug Delivery Enhancement by Compounds of Natural Origin. Molecules, 16(12), 10507-10540.
Gallagher, F. A., Kettunen, M. I., Day, S. E., Hu, D.-E., Ardenkjaer-Larsen, J. H., Zandt, R., Jensen, P. R., Karlsson, M., Golman, K., & Lerche, M. H. (2008). Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature, 453(7197), 940-943.
Giommarelli, C., Zuco, V., Favini, E., Pisano, C., Dal Piaz, F., De Tommasi, N., & Zunino, F. (2010). The enhancement of antiproliferative and proapoptotic activity of HDAC inhibitors by curcumin is mediated by Hsp90 inhibition. Cellular and Molecular Life Sciences, 67(6), 995-1004.
Gupta, A. P., Khan, S., Manzoor, M. M., Yadav, A. K., Sharma, G., Anand, R., & Gupta, S. (2017). Chapter 10 - Anticancer Curcumin: Natural Analogues and Structure-Activity Relationship. In R. Atta ur (Ed.), Studies in Natural Products Chemistry (Vol. 54, pp. 355-401). Elsevier.
He, C., Hu, Y., Yin, L., Tang, C., & Yin, C. (2010). Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials, 31(13), 3657-3666.
He, W., Lu, Y., Qi, J., Chen, L., Hu, F., & Wu, W. (2013). Nanoemulsion-templated shell-crosslinked nanocapsules as drug delivery systems. International Journal of Pharmaceutics, 445(1-2), 69-78.
Heger, M., van Golen, R. F., Broekgaarden, M., & Michel, M. C. (2014). The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacological Reviews, 66(1), 222-307.
Hilchie, A. L., Furlong, S. J., Sutton, K., Richardson, A., Robichaud, M. R., Giacomantonio, C. A., Ridgway, N. D., & Hoskin, D. W. (2010). Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria. Nutrition and Cancer, 62(3), 379-389.
Hu, Y., Litwin, T., Nagaraja, A. R., Kwong, B., Katz, J., Watson, N., & Irvine, D. J. (2007). Cytosolic Delivery of Membrane-Impermeable Molecules in Dendritic Cells Using pH-Responsive Core−Shell Nanoparticles. Nano Letters, 7(10), 3056-3064.
Huang, Y.-C., & Li, R.-Y. (2014). Preparation and characterization of antioxidant nanoparticles composed of chitosan and fucoidan for antibiotics delivery. Marine Drugs, 12(8), 4379-4398.
Huang, Y. C., & Yang, Y. T. (2016). Effect of basic fibroblast growth factor released from chitosan–fucoidan nanoparticles on neurite extension. Journal of Tissue Engineering and Regenerative Medicine, 10(5), 418-427.
Hussein, U. K., Mahmoud, H. M., Farrag, A. G., & Bishayee, A. (2015). Chemoprevention of Diethylnitrosamine-Initiated and Phenobarbital-Promoted Hepatocarcinogenesis in Rats by Sulfated Polysaccharides and Aqueous Extract of Ulva lactuca. Integrative Cancer Therapies, 14(6), 525-545.
Indira Priyadarsini, K. (2013). Chemical and structural features influencing the biological activity of curcumin. Current Pharmaceutical Design, 19(11), 2093-2100.
Iversen, T.-G., Skotland, T., & Sandvig, K. (2011). Endocytosis and intracellular transport of nanoparticles: Present knowledge and need for future studies. Nano Today, 6(2), 176-185.
Jahan, S. T., Sadat, S. M. A., Walliser, M., & Haddadi, A. (2017). Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer. J Drug Deliv, 2017, 9090325.
Jayakumar, R., Prabaharan, M., Nair, S. V., Tokura, S., Tamura, H., & Selvamurugan, N. (2010). Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications. Progress in Materials Science, 55(7), 675-709.
Jo, D. H., Kim, J. H., Lee, T. G., & Kim, J. H. (2015). Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine, 11(7), 1603-1611.
Joe, B., Vijaykumar, M., & Lokesh, B. (2004). Biological properties of curcumin-cellular and molecular mechanisms of action. Critical Reviews in Food Science and Nutrition, 44(2), 97-111.
Kadam, R. S., Bourne, D. W., & Kompella, U. B. (2012). Nano-advantage in enhanced drug delivery with biodegradable nanoparticles: contribution of reduced clearance. Drug Metabolism and Disposition, 40(7), 1380-1388.
Kamel, A. E., Fadel, M., & Louis, D. (2019). Curcumin-loaded nanostructured lipid carriers prepared using Peceol™ and olive oil in photodynamic therapy: development and application in breast cancer cell line. International Journal of Nanomedicine, 14, 5073.
Karimi, M., Ghasemi, A., Zangabad, P. S., Rahighi, R., Basri, S. M. M., Mirshekari, H., Amiri, M., Pishabad, Z. S., Aslani, A., & Bozorgomid, M. (2016). Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chemical Society Reviews, 45(5), 1457-1501.
Kesavan, S., Meena, K. S., Sharmili, S. A., Govindarajan, M., Alharbi, N. S., Kadaikunnan, S., Khaled, J. M., Alobaidi, A. S., Alanzi, K. F., & Vaseeharan, B. (2021). Ulvan loaded graphene oxide nanoparticle fabricated with chitosan and d-mannose for targeted anticancer drug delivery. Journal of Drug Delivery Science and Technology, 65, 102760.
Kidgell, J. T., Magnusson, M., de Nys, R., & Glasson, C. R. (2019). Ulvan: A systematic review of extraction, composition and function. Algal Research, 39, 101422.
Kosanić, M., Ranković, B., & Stanojković, T. (2015). Biological activities of two macroalgae from Adriatic coast of Montenegro. Saudi Journal of Biological Sciences, 22(4), 390-397.
Lerchen, H. G., Baumgarten, J., Piel, N., & Kolb‐Bachofen, V. (1999). Lectin‐Mediated Drug Targeting: Discrimination of Carbohydrate‐Mediated Cellular Uptake between Tumor and Liver Cells with Neoglycoconjugates Carrying Fucose Epitopes Regioselectively Modified in the 3‐Position. Angewandte Chemie International Edition, 38(24), 3680-3683.
Li, J., Jiang, F., Chi, Z., Han, D., Yu, L., & Liu, C. (2018). Development of Enteromorpha prolifera polysaccharide-based nanoparticles for delivery of curcumin to cancer cells. International Journal of Biological Macromolecules, 112, 413-421.
Li, P., Wang, Y., Peng, Z., She, F., & Kong, L. (2011). Development of chitosan nanoparticles as drug delivery systems for 5-fluorouracil and leucovorin blends. Carbohydrate Polymers, 85(3), 698-704.
Lim, W. Q., Phua, S. Z. F., Xu, H. V., Sreejith, S., & Zhao, Y. (2016). Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy. Nanoscale, 8(25), 12510-12519.
Lin, Y. H., Mi, F. L., Chen, C. T., Chang, W. C., Peng, S. F., Liang, H. F., & Sung, H. W. (2007). Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules, 8(1), 146-152.
Liu, Liu, J., Xu, H., Zhang, Y., Chu, L., Liu, Q., Song, N., & Yang, C. (2014). Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery. Int J Nanomedicine, 9, 197-207.
Liu, J., Huang, Y., Kumar, A., Tan, A., Jin, S., Mozhi, A., & Liang, X.-J. (2014). pH-Sensitive nano-systems for drug delivery in cancer therapy. Biotechnology Advances, 32(4), 693-710.
Lu, K.-Y., Jheng, P.-R., Lu, L.-S., Rethi, L., Mi, F.-L., & Chuang, E.-Y. (2021). Enhanced anticancer effect of ROS-boosted photothermal therapy by using fucoidan-coated polypyrrole nanoparticles. International Journal of Biological Macromolecules, 166, 98-107.
Łuczak, J., Latowska, A., & Hupka, J. (2015). Micelle formation of Tween 20 nonionic surfactant in imidazolium ionic liquids. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 471, 26-37.
Ma, X., Wang, Y., Zhao, T., Li, Y., Su, L.-C., Wang, Z., Huang, G., Sumer, B. D., & Gao, J. (2014). Ultra-pH-sensitive nanoprobe library with broad pH tunability and fluorescence emissions. Journal of the American Chemical Society, 136(31), 11085-11092.
Maheshwari, M., & Shishu. (2010). Comparative bioavailability of curcumin, turmeric and Biocurcumax™ in traditional vehicles using non-everted rat intestinal sac model. Journal of Functional Foods, 2(1), 60-65.
Manivasagan, P., & Oh, J. (2016). Marine polysaccharide-based nanomaterials as a novel source of nanobiotechnological applications. International Journal of Biological Macromolecules, 82, 315-327.
Mao, W., Zang, X., Li, Y., & Zhang, H. (2006). Sulfated polysaccharides from marine green algae Ulva conglobata and their anticoagulant activity. Journal of Applied Phycology, 18(1), 9-14.
Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., Stein, K. D., Alteri, R., & Jemal, A. (2016). Cancer treatment and survivorship statistics, 2016. CA: a Cancer Journal for Clinicians, 66(4), 271-289.
Mirzaei, A., Jahanshahi, F., Khatami, F., Reis, L. O., & Aghamir, S. M. K. (2022). Human prostate cancer cell epithelial-to-mesenchymal transition as a novel target of arsenic trioxide and curcumin therapeutic approach. Tissue and Cell, 76, 101805.
Misra, S., Hascall, V. C., Markwald, R. R., & Ghatak, S. (2015). Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer [Review]. Frontiers in Immunology, 6.
Moussa, Z., Hmadeh, M., Abiad, M. G., Dib, O. H., & Patra, D. (2016). Encapsulation of curcumin in cyclodextrin-metal organic frameworks: Dissociation of loaded CD-MOFs enhances stability of curcumin. Food Chemistry, 212, 485-494.
Mukerjee, A., & Vishwanatha, J. K. (2009). Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Research, 29(10), 3867-3875.
Neuman, M. G., Haber, J. A., Malkiewicz, I. M., Cameron, R. G., Katz, G. G., & Shear, N. H. (2002). Ethanol signals for apoptosis in cultured skin cells. Alcohol, 26(3), 179-190.
Nishiyama, N. (2007). Nanomedicine: nanocarriers shape up for long life. Nature Nanotechnology, 2(4), 203.
Paul, P., Malakar, A. K., & Chakraborty, S. (2019). The significance of gene mutations across eight major cancer types. Mutation Research/Reviews in Mutation Research, 781, 88-99.
Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2020). Nanocarriers as an emerging platform for cancer therapy. Nano-Enabled Medical Applications, 61-91.
Pengzhan, Y., Ning, L., Xiguang, L., Gefei, Z., Quanbin, Z., & Pengcheng, L. (2003). Antihyperlipidemic effects of different molecular weight sulfated polysaccharides from Ulva pertusa (Chlorophyta). Pharmacological Research, 48(6), 543-549.
Perevedentseva, E., Hong, S.-F., Huang, K.-J., Chiang, I.-T., Lee, C.-Y., Tseng, Y.-T., & Cheng, C.-L. (2013). Nanodiamond internalization in cells and the cell uptake mechanism. Journal of Nanoparticle Research, 15(8), 1-12.
Plante, M. K., Arscott, W. T., Folsom, J. B., Tighe, S. W., Dempsey, R. J., & Wesley, U. V. (2013). Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells. Prostate Cancer Prostatic Dis, 16(1), 16-22.
Prasad, S., Gupta, S. C., Tyagi, A. K., & Aggarwal, B. B. (2014). Curcumin, a component of golden spice: from bedside to bench and back. Biotechnology Advances, 32(6), 1053-1064.
Qi, H., Zhang, Q., Zhao, T., Chen, R., Zhang, H., Niu, X., & Li, Z. (2005). Antioxidant activity of different sulfate content derivatives of polysaccharide extracted from Ulva pertusa (Chlorophyta) in vitro. International Journal of Biological Macromolecules, 37(4), 195-199.
Rahimi, H. R., Nedaeinia, R., Shamloo, A. S., Nikdoust, S., & Oskuee, R. K. (2016). Novel delivery system for natural products: Nano-curcumin formulations. Avicenna journal of Phytomedicine, 6(4), 383.
Saravanakumar, K., Hu, X., Ali, D. M., & Wang, M.-H. (2019). Emerging strategies in stimuli-responsive nanocarriers as the drug delivery system for enhanced cancer therapy. Current Pharmaceutical Design, 25(24), 2609-2625.
Saravanakumar, K., Mariadoss, A. V. A., Sathiyaseelan, A., Venkatachalam, K., Hu, X., & Wang, M.-H. (2021). pH-sensitive release of fungal metabolites from chitosan nanoparticles for effective cytotoxicity in prostate cancer (PC3) cells. Process Biochemistry, 102, 165-172.
Sharma, R., Gescher, A., & Steward, W. (2005). Curcumin: the story so far. European Journal of Cancer, 41(13), 1955-1968.
Shehzad, A., Wahid, F., & Lee, Y. S. (2010). Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Archiv der Pharmazie, 343(9), 489-499.
Song, Q., Yin, Y., Shang, L., Wu, T., Zhang, D., Kong, M., Zhao, Y., He, Y., Tan, S., & Guo, Y. (2017). Tumor microenvironment responsive nanogel for the combinatorial antitumor effect of chemotherapy and immunotherapy. Nano Letters, 17(10), 6366-6375.
Stowell, S. R., Arthur, C. M., Dias-Baruffi, M., Rodrigues, L. C., Gourdine, J.-P., Heimburg-Molinaro, J., Ju, T., Molinaro, R. J., Rivera-Marrero, C., & Xia, B. (2010). Innate immune lectins kill bacteria expressing blood group antigen. Nature Medicine, 16(3), 295-301.
Sun, M., Su, X., Ding, B., He, X., Liu, X., Yu, A., Lou, H., & Zhai, G. (2012). Advances in nanotechnology-based delivery systems for curcumin. Nanomedicine (Lond), 7(7), 1085-1100.
Tan, B. L., & Norhaizan, M. E. (2019). Curcumin combination chemotherapy: The implication and efficacy in cancer. Molecules, 24(14), 2527.
Thanh, T. T. T., Quach, T. M. T., Nguyen, T. N., Vu Luong, D., Bui, M. L., & Tran, T. T. V. (2016). Structure and cytotoxic activity of ulvan extracted from green seaweed Ulva lactuca. International Journal of Biological Macromolecules, 93, 695-702.
Thapa, R. K., Cazzador, F., Grønlien, K. G., & Tønnesen, H. H. (2020). Effect of curcumin and cosolvents on the micellization of Pluronic F127 in aqueous solution. Colloids and Surfaces B: Biointerfaces, 195, 111250.
Thomas, G. B., Rader, L. H., Park, J., Abezgauz, L., Danino, D., DeShong, P., & English, D. S. (2009). Carbohydrate modified catanionic vesicles: probing multivalent binding at the bilayer interface. Journal of the American Chemical Society, 131(15), 5471-5477.
Tziveleka, L.-A., Ioannou, E., & Roussis, V. (2019). Ulvan, a bioactive marine sulphated polysaccharide as a key constituent of hybrid biomaterials: A review. Carbohydrate Polymers, 218, 355-370.
Umh, H. N., & Kim, Y. (2014). Sensitivity of nanoparticles’ stability at the point of zero charge (PZC). Journal of Industrial and Engineering Chemistry, 20(5), 3175-3178.
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011). Endosomal escape pathways for delivery of biologicals. Journal of Controlled Release, 151(3), 220-228.
Wang, W., Meng, Q., Li, Q., Liu, J., Zhou, M., Jin, Z., & Zhao, K. (2020). Chitosan Derivatives and Their Application in Biomedicine. International Journal of Molecular Sciences, 21(2), 487.
Wang, Y., Gao, J., Gu, G., Li, G., Cui, C., Sun, B., & Lou, H. (2011). In situ RBL receptor visualization and its mediated anticancer activity for solasodine rhamnosides. ChemBioChem, 12(16), 2418-2420.
Xu, L., Liu, X., Li, Y., Yin, Z., Jin, L., Lu, L., Qu, J., & Xiao, M. (2019). Enzymatic rhamnosylation of anticancer drugs by an α-l-rhamnosidase from Alternaria sp. L1 for cancer-targeting and enzyme-activated prodrug therapy. Applied Microbiology and Biotechnology, 103(19), 7997-8008.
Yallapu, M. M., Jaggi, M., & Chauhan, S. C. (2010). β-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids and Surfaces B: Biointerfaces, 79(1), 113-125.
Yallapu, M. M., Jaggi, M., & Chauhan, S. C. (2012). Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discovery Today, 17(1-2), 71-80.
Yhee, J. Y., Son, S., Kim, N., Choi, K., & Kwon, I. C. (2014). Theranostic applications of organic nanoparticles for cancer treatment. Mrs Bulletin, 39(3), 239-249.
Yu, Z., Ma, L., Ye, S., Li, G., & Zhang, M. (2020). Construction of an environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan nanoparticle drug delivery system to alleviate inflammation and oxidative stress. Carbohydrate Polymers, 236, 115972.
Zhao, T., Huang, G., Li, Y., Yang, S., Ramezani, S., Lin, Z., Wang, Y., Ma, X., Zeng, Z., & Luo, M. (2016). A transistor-like pH nanoprobe for tumour detection and image-guided surgery. Nature Biomedical Engineering, 1(1), 1-8.
Zheng, M., Han, B., Yang, Y., & Liu, W. (2011). Synthesis, characterization and biological safety of O-carboxymethyl chitosan used to treat Sarcoma 180 tumor. Carbohydrate Polymers, 86(1), 231-238.
Zong, L., Cheng, G., Liu, S., Pi, Z., Liu, Z., & Song, F. (2019). Reversal of multidrug resistance in breast cancer cells by a combination of ursolic acid with doxorubicin. Journal of Pharmaceutical and Biomedical Analysis, 165, 268-275.