Specific drug delivery efficiently induced human breast tumor regression using a lipoplex by non-covalent association with anti-tumor antibodies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-06

AUTHORS

Yu-Ling Lin, Nu-Man Tsai, Chia-Hung Chen, Yen-Ku Liu, Chung-Jen Lee, Yi-Lin Chan, Yu-Shan Wang, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao Ching Wang, Kwan-Hwa Chi, Kuang-Wen Liao

ABSTRACT

BACKGROUND: A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h. RESULTS: Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model. CONCLUSIONS: LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy. More... »

PAGES

25

Journal

TITLE

Journal of Nanobiotechnology

ISSUE

1

VOLUME

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12951-019-0457-3

DOI

http://dx.doi.org/10.1186/s12951-019-0457-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111954551

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30728015


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26 schema:description BACKGROUND: A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h. RESULTS: Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model. CONCLUSIONS: LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.
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34 HER2-negative Hs578T cells
35 HER2-positive SKBR3 cells
36 HER2/
37 HER2/neu-negative cells
38 HER2/neu-positive cells
39 Herceptin
40 Herceptin complexes
41 Hs578T cells
42 IVIS images
43 LPPC
44 LPPC displays important clinical implications
45 LPPC-delivery system
46 LPPC/Herceptin complexes
47 Lipodox
48 PEG-PEI complexes
49 SKBR3 cells
50 T cells
51 ability
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53 anti-tumor antibodies
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56 association
57 average size
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59 breast cancer cells
60 breast cancer therapy
61 breast tumor regression
62 cancer cells
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69 complexes
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71 curcumin/LPPC/Herceptin complexes
72 cytotoxic activity
73 delivery
74 delivery of drugs
75 delivery system
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77 dosage
78 drug delivery
79 drug treatment
80 drug/LPPC/Herceptin complexes
81 drugs
82 efficacy
83 epidermal growth factor receptor 2
84 factor receptor 2
85 group
86 growth factor receptor 2
87 human breast tumor regression
88 human epidermal growth factor receptor 2
89 images
90 immunocomplexes
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92 implications
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94 lipoplexes
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