Stem cells loaded with nanoparticles as a drug carrier for in vivo breast cancer therapy

Abstract

A novel anti-cancer drug carrier, mesenchymal stem cells (MSCs) encapsulating drug-loaded hollow silica nanoparticles, is used to carry a photosensitizer drug and deliver it to breast tumors, due to the natural high tumor affinity of the MSCs, and inhibit tumor growth by photo dynamic therapy. This new strategy for delivering a photo sensitizer to tumors by using tumor-affinitive MSCs addresses the challenge of the accumulation of photosensitizer drugs in tumors in photodynamic therapy.

Keywords: cancer; mesenchymal stem cells (MSCs); nanoparticles; photodynamic therapy; photosensitizers.

Figure 1

Schematic illustration of loading PS-loaded SiO₂NPs into MSCs and using the resultant PS-loaded MSCs to kill cancer cells and inhibit tumor growth by photodynamic therapy (PDT). The natural high tumor affinity of MSCs is exploited to allow the retention of PS-loaded MSCs in tumors and the consequent accumulation of PS in tumors for effective destruction of tumors by PDT. SiO₂ NP: silica nanoparticle; Pp-18: purpurin-18; PS: photosensitizer; ROS: reactive oxygen species.

Figure 2

In vitro cellular uptake of SiO₂NPs loaded with FITC-labeled peptide by MSCs. MSCs without interacted with SiO₂NPs were used as a control. Top: Fluorescence images showing DAPI-stained nuclei and FITC-stained SiO₂NPs internalized in MSCs. Bottom: FACS analysis of MSCs incubated with FITC-stained SiO₂NPs for 6 h, showing more than 90% of the cells were loaded with FITC-stained SiO₂NPs.

Figure 3

In vivo PDT treatment on tumors one day after co-injection of MCF-7 cancer cells and MSCs with (group 1: PS-SiO₂NPs-MSCs group) or without (group 2: control MSCs group) PS-SiO₂NPs loaded. a) Pictures showing the size of tumors isolated from mice (PS-SiO₂NPs-MSCs group: MSCs were loaded with PS-SiO₂NPs and laser light was applied to trigger PDT; MSCs group: control where MSCs were not loaded with PS-SiO₂NPs but laser light was still applied). b) The weight of tumors of PS-SiO₂NPs-MSCs group and control MSCs group. c) A picture of a mouse showing the size of tumors one day after light treatment (the tumor on the left and right side was treated with PS-SiO₂NPs-MSCs and MSCs, respectively. Both tumors were highlighted by an oval). d) H&E stained tissue sections of tumors (left: PS-SiO₂NPs-MSCs group; right: MSCs group). e) TUNEL stained tissue sections of tumors (left: PS-SiO₂NPs-MSCs group; right: MSCs group). The white arrows indicate apoptotic cells stained with TUNEL. The asterisk in (b) indicates significant difference between PS-SiO₂NPs-MSCs group and MSCs group at p < 0.05.