期刊
JOURNAL OF NANOBIOTECHNOLOGY
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12951-019-0457-3
关键词
Lipo-PEG-PEI complex; Curcumin; Doxorubicin; Herceptin; Drug delivery
资金
- Ministry of Science and Technology of Taiwan [MOST 103-2320-B-009-008, MOST 105-2314-B-341-005, MOST105-2314-B-182A-133]
- Shin Kong Wu Ho-Su Memorial Hospital Foundation [SKH-8302-103-DR-34]
- Chang-Gung Memorial Hospital Research Foundation [CMRPG2F0141-2, CMRPG2D0091-3]
BackgroundA 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 1h.ResultsDrug-loaded LPPC have an average size about 250nm and a zeta potential of about 40mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280nm and the zeta potentials were about 23mV. 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.ConclusionsLPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.
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