Recent advances in liposome formulations for breast cancer therapeutics

Abstract

Among many nanoparticle-based delivery platforms, liposomes have been particularly successful with many formulations passed into clinical applications. They are well-established and effective gene and/or drug delivery systems, widely used in cancer therapy including breast cancer. In this review we discuss liposome design with the targeting feature and triggering functions. We also summarise the recent progress (since 2014) in liposome-based therapeutics for breast cancer including chemotherapy and gene therapy. We finally identify some challenges on the liposome technology development for the future clinical translation.

Keywords: Breast cancer; Cancer therapy; Liposomal delivery; Triggerable liposomes.

Fig.1

Schematic diagram of liposome-based delivery systems with various functions

Fig.2

a Drug release from thermo-sensitive liposomes incorporating DTX (DTX-TL) over time determined at 37 °C and 42 °C, respectively. When temperature was achieved the phase transition temperature (42 °C) of DTX-TL, release of DTX was increased due to thermosensitivity of DTX-TL. b Tumour growth of mice bearing MCF-7 breast carcinoma (n = 9) after the treatment with saline, DTX injection (DTX-I) (5.0 mg/kg) or DTX-TL injection (2.5, 5.0, and 10.0 mg/kg) for every 4 days (a total of four injections). The tumour was then heated at 42 °C for 30 min after the injection. The volume of tumour treated with DTX-TL (10.0 mg/kg) was significantly reduced, suggesting the highest treatment efficacy of the DTX-TL. c Photograph of tumours collected from the mice treated with the same conditions as b, adapted from ref. [123]

Fig.3

a Schematic illustration of anti-CD44 aptamer (Apt-1) conjugated liposomes loaded with siRNA–protamine complex (siRNA/prot). b In vitro Luc2 gene silencing in MDA-MB-231-Luc2-GFP cells after the treatments with scramble siRNA and anti-luc2 siRNA in different forms: free, siRNA–proamine complex (siRNA/prot), loaded in liposomes (siRNA/prot ⊂ lip), and loaded in Apt1-functionalized liposomes (siRNA/prot ⊂ lip-Apt1). Only siRNA/prot ⊂ lip and siRNA/prot ⊂ lip-Apt1 induced specific Luc2 gene expression reduction. Among these two groups, siRNA/prot ⊂ lip-Apt1 exhibited higher inhibiting capability, which may be attributed to its higher cellular uptake compared with non-functionalised liposomes. c Q-Polymerise Chain Reaction (qPCR) results demonstrated the Luc gene silencing effect in a mouse model bearing MDA-MB-231-Luc2-GFP cells treated with PBS, liposomes loaded with scrambled siRNA/prot (scr siRNA ⊂ lip), liposomes loaded with luc2 siRNA/prot (luc2-siRNA/prot ⊂ lip), aptamer-functionalized liposomes loaded with scrambled siRNA/prot (scr siRNA ⊂ lip-Apt1), and aptamer-functionalized liposomes loaded with Luc2 siRNA/prot (Luc2-siRNA ⊂ lip-Apt1). d Bioluminescence signals from tumours of mice treated with different siRNA formulations as c, adapted from ref. [167]

Fig.4

a Schematic diagram of the engineered liposome–hydrogel structure and CRISPR Cas9 genetic materials. In vitro Lnc2 gene editing efficacy of liposome-formulated CRISPR in b MDA-MB-231 cells and c MDA-MB-436 cells. Cells were treated with PBS, free Lcn2 CRISPR knockout plasmid (free Lcn2KO), tNLGs encapsulating scrambled CRISPR plasmid (tNLG-SCR), a complex of ultracruz and Lcn2 CRISPR knockout plasmid (Ultracruz-Lcn2KO), a nonspecific liposome–hydrogel encapsulating Lcn2 CRISPR knockout plasmid (nNLGLcn2KO), and a TNBC-specific liposome–hydrogel encapsulating Lcn2 CRISPR knockout plasmid (tNLG-Lcn2KO). d Weekly tumour volume measurement demonstrating tumour progression over 84 days after the different treatments indicated in the figure, adapted from ref. [200]