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

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

doi:10.1186/s12951-019-0457-3

Abstract

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 1 h.ResultsDrug-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.ConclusionsLPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.

Highlights

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
Characteristics of drug loaded LPPC/Herceptin Anti-tumor drugs such as curcumin are loaded into LPPC by incubation at room temperature and remove the non-encapsulated curcumin by centrifugation
The LPPC bound Herceptin was stable on the LPPC or Curcumin/LPPC (Additional file 1: Figure S1)

Summary

Introduction

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. Covalent conjugation of the targeting molecules, such as with cell-specific peptides (RGD and GE11 peptides) [5,6,7] and monoclonal antibodies (anti-HER2/ neu and anti-EGFR antibodies) [1, 8,9,10], has further improved the efficacy compared with drug-encapsulated particles. Cationic P(MDS-co-CES) micelles were developed, which bind Herceptin or TRAIL via hydrogen bonds and/or hydrophobic interactions and encapsulates doxorubicin or paclitaxel to target cancer cells in vitro [19,20,21]. The in vivo efficacy of this approach has not yet been displayed

Methods

Results

Conclusion