Nanoparticle-mediated targeted drug delivery for breast cancer treatment

Abstract

Breast cancer (BC) is the most common malignancy in women worldwide, and one of the deadliest after lung cancer. Currently, standard methods for cancer therapy including BC are surgery followed by chemotherapy or radiotherapy. However, both chemotherapy and radiotherapy often fail to treat BC due to the side effects that these therapies incur in normal tissues and organs. In recent years, various nanoparticles (NPs) have been discovered and synthesized to be able to selectively target tumor cells without causing any harm to the healthy cells or organs. Therefore, NPs-mediated targeted drug delivery systems (DDS) have become a promising technique to treat BC. In addition to their selectivity to target tumor cells and reduce side effects, NPs have other unique properties which make them desirable for cancer treatment such as low toxicity, good compatibility, ease of preparation, high photoluminescence (PL) for bioimaging in vivo, and high loadability of drugs due to their tunable surface functionalities. In this study, we summarize with a critical analysis of the most recent therapeutic studies involving various NPs-mediated DDS as alternatives for the traditional treatment approaches for BC. It will shed light on the significance of NPs-mediated DDS and serve as a guide to seeking for the ideal methodology for future targeted drug delivery for an efficient BC treatment.

Keywords: Bioimaging; Biomarkers; Breast cancer; Drug delivery; Nanoparticles.

Figure 1.

A diagram of different types of NPs used in BC research for targeted DDS.

Figure 2.

The schematic illustration of the layer-by-layer drug delivery platform of poly-L-arginine NPs. The figure is adapted with permission from ref. ^[15].

Figure 3.

Schematic illustration of the Au-Poly(L-aspartate-DOX)-b-PEG-OH/*FA NP and its pH-triggered drug release (*FA – Folic acid). The figure is adapted with permission from ref.^[84].

Figure 4.

Individual temperature dosages over tumor areas. (a). By using tumor surface temperature during hyperthermia treatment, median temperature dosages were calculated as cumulative equivalent minutes (CEM43T90) and displayed as box plots. (b). Example of a treatment sequence within the alternating magnetic field (AMF), the corresponding temperature distribution over the tumor surface and the effect on tumor volume. (c). Intratumoral distribution of SPIONs (MF66-N6LDOX) was determined using micro computed tomography 24 h prior to the first hyperthermia treatment. The figure is adapted with permission from ref. ^[102].

Figure 5.

Optical properties and potential applications of QDs in BC research studies. Commonly used QDs are core–shell structure encapsulated with amphiphilic polymers carrying chemically active groups. Compared with traditional organic dyes, QDs show excellent optical properties (A). After being coupled with active molecules, QDs can be adapted for tissues imaging, such as studying biomarker interactions (B) and evaluating prognostic biomarkers (C), and for in vivo imaging such as mapping auxiliary lymphatic system (D), showing BC (BC) xenograft (E) and detecting BC metastasis (F) in BC research studies. The figure is adapted with permission from ref. [109]

Figure 6.

Various pore geometrics of mesoporous structure (a) 2D hexagonal p6 mm, (b) bicontinuous cubic Ia3d, (c) bicontinuous cubic pn3 m, (d) cage type pm3n, (e) cage type Im3 m. The figure is adapted with permission from ref. ^[117].

Figure 7.

Tumor growth inhibition of xenografts established from MCF-7/MDR cells in nude mice. (A) MCF-7/MDR cancer cells were subcutaneously injected into mice 7 days before treatment with MSNs (gray boxes). These animals received six i.v. injections (red boxes) every 3-6 days (green boxes) for 30 days as shown. (B) Comparison of the tumor inhibition effect of Dox-loaded MSNs containing Pgp siRNA versus other treatment groups: saline, empty MSNs, free Dox, free siRNA, Dox-loaded MSNs without siRNA, and Dox-loaded MSNs containing scrambled siRNA. Following sacrifice of the animals, tumor tissues were collected and weighed to determine the tumor inhibition rate. (/) p<0.05, compared to saline; (#) p<0.05, compared to Dox-loaded MSNs without siRNA; ($) p<0.05, compared to Dox-loaded MSNs with scramble (X) siRNA. (C) Photograph of the collected tumor tissues for each treatment group. The figure is adapted with permission from ref. ^[119].

Figure 8.

Confocal microscopy images of MCF-7 cells incubated with CDs- Dox (A, B, C and D) and free delivery of Dox (E, F, G and H) for 4 h, respectively. The cell nuclei were stained with DAPI and the concentration of Dox was 1 μg mL⁻¹. The cell nuclei, Dox and CDs exhibited blue, red and green fluorescence, respectively. The scale bars are 25 μm in all the images. The figure is adapted with permission from ref. ^[162].