Engineering Remotely Triggered Liposomes to Target Triple Negative Breast Cancer

Abstract

Triple Negative Breast Cancer (TNBC) continues to present a challenge in the clinic, as there is still no approved targeted therapy. TNBC is the worst sub-type of breast cancer in terms of prognosis and exhibits a deficiency in estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. One possible option for the treatment of TNBC is chemotherapy. The issue with many chemotherapy drugs is that their effectiveness is diminished due to poor water solubility, and the method of administration directly or with a co-solvent intravenously can lead to an increase in toxicity. The issues of drug solubility can be avoided by using liposomes as a drug delivery carrier. Liposomes are engineered, biological nanoconstructs that possess the ability to encapsulate both hydrophobic and hydrophilic drugs and have been clinically approved to treat cancer. Specific targeting of cancer cell receptors through the use of ligands conjugated to the surface of drug-loaded liposomes could lessen damage to normal, healthy tissue. This study focuses on polyethylene glycol (PEG)-coated, folate conjugated, benzoporphyrin derivative (BPD)-loaded liposomes for treatment via photodynamic therapy (PDT). The folate receptor is over expressed on TNBC cells so these liposomes are targeted for greater uptake into cancer cells. PDT involves remotely irradiating light at 690 nm to trigger BPD, a hydrophobic photosensitive drug, to form reactive oxygen species that cause tumor cell death. BPD also displays a fluorescence signal when excited by light making it possible to image the fluorescence prior to PDT and for theranostics. In this study, free BPD, non-targeted and folate-targeted PEGylated BPD-loaded liposomes were introduced to a metastatic breast cancer cell line (MDA-MB-231) in vitro. The liposomes were reproducibly synthesized and characterized for size, polydispersity index (PDI), zeta potential, stability, and BPD release kinetics. Folate competition tests, fluorescence confocal imaging, and MTT assay were used to observe and quantify targeting effectiveness. The toxicity of BPD before and after PDT in monolayer and 3D in vitro cultures with TNBC cells was observed. This study may contribute to a novel nanoparticle-mediated approach to target TNBC using PDT.

Photodynamic therapy in cancer treatment - an update review

“…One more example of how the use of a targeting agent would ideally improve the selectivity of PDT for the tumor tissue has been shown in a recent study. By using polyethylene glycol-coated, folate conjugated, benzoporphyrin derivative-loaded liposomes for PDT treatment of breast cancer cells, the researchers have reported that these liposomes are targeted for are greater uptake into TNBC cancer cells [136] . Therefore, focusing on the molecular differences of cell death mechanisms induced by PDT, starting with an optimized PS choice and conditions of its delivery and activation, will certainly provide valuable clues for the development of new therapeutic strategies aiming at improving the efficacy of PDT against cancer cells [7,15] .…”

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy

“…Other recent publications using PMs as delivery carrier for PDT or for a combined therapy confirmed the high efficiency of this type of nanocarriers (Dehghankelishadi and Dorkoosh 2016, Pellosi et al 2016a, b, 2017. …”

“…Additionally, their nanometric size (classically 60-120 nm) confer them a high loading capacity of the therapeutic agent. All these properties make this type of systems effective vehicles for the delivery of drugs in PDT (Banerjee 2001, Chen et al 2005, Sneider et al 2017. Certain improvements in liposomal technology and molecular biology have been done, allowing them to have targeting power in order to achieve selective delivery to specific biological targets (Medina et al 2004).…”

Liposomes Aid Curcumin's Combat with Cancer in a Breast Tumor Model

“…While extensive work has been conducted with the liposomal CUR formulation, our study focused on aiding the selectivity of CUR by actively targeting the liposomes to the overexpressed receptors on cancer cells. This was achieved by surface modification of liposomes with folic acid which binds to overexpressed folate receptors (FRα) on tumor cells [51][52][53][54][55][56]. FRα, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, belongs to the folate receptor family which uses unidirectional transport of folate into cells [52,56,57].…”

“…To our knowledge, a direct comparative results showing the difference in curcumin efficiency between non-malignant and cancer cells using folate decorated liposomes has not been demonstrated thus far. To test this comparison in vitro and challenge the selective attribute of curcumin when encapsulated in a targeted liposomal modality, we decided to conduct a parallel study using non-malignant mammary epithelial cells, MCF-12A, and triple negative breast cancer cells (TNBC), MDA-MB-231 [51,[59][60][61][62][63].…”