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

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.

• 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
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 17 Issue 1 Pg. 25 (Feb 06 2019) ISSN: 1477-3155 [Electronic] England
• PMID: 30728015 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Liposomes
• poly(ethylene glycol)-co-poly(ethyleneimine)
• Polyethylene Glycols
• Doxorubicin
• Polyethyleneimine
• ERBB2 protein, human
• Receptor, ErbB-2
• Curcumin
• Trastuzumab

Topics

• Animals
• Antineoplastic Agents (administration & dosage, immunology)
• Breast Neoplasms (drug therapy, immunology, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Curcumin (administration & dosage)
• Doxorubicin (administration & dosage)
• Drug Liberation
• Female
• Heterografts
• Humans
• Liposomes
• MCF-7 Cells
• Mice, Inbred BALB C
• Particle Size
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (analogs & derivatives, chemistry)
• Receptor, ErbB-2 (metabolism)
• Surface Properties
• Trastuzumab (administration & dosage, immunology)