Eradicating the tumor "seeds": nanomedicines-based therapies against cancer stem cells

Abstract

Objectives: Cancer stem cells (CSCs), a small subpopulation of cells with high tumorigenesis and strong intrinsic drug resistance, exhibit self-renewal and differentiation abilities. CSCs play a crucial role in tumor progression, drug resistance, recurrence and metastasis,and conventional therapy is not enough to eradicate them. Therefore, developing novel therapies targeting CSCs to increase drug sensitivity and preventing relapse is essential. The objective of this review is to present nanotherapies that target and eradicate the tumor "seeds".

Evidence acquisition: Evidence was collected and sorted from the literature ranging from 2000 to 2022, using appropriate keywords and key phrases as search terms within scientific databases such as Web of Science, PubMed and Google Scholar.

Results: Nanoparticle drug delivery systems have been successfully applied to gain longer circulation time, more precise targeting capability and better stability during cancer treatment. Nanotechnology-based strategies that have been used to target CSCs, include (1) encapsulating small molecular drugs and genes by nanotechnology, (2) targeting CSC signaling pathways, (3) utilizing nanocarriers targeting for specific markers of CSCs, (4) improving photothermal/ photodynamic therapy (PTT/PDT), 5)targeting the metabolism of CSCs and 6) enhancing nanomedicine-aided immunotherapy.

Conclusion: This review summarizes the biological hallmarks and markers of CSCs, and the nanotechnology-based therapies to kill them. Nanoparticle drug delivery systems are appropriate means for delivering drugs to tumors through enhanced permeability and retention (EPR) effect. Furthermore, surface modification with special ligands or antibodies improves the recognition and uptake of tumor cells or CSCs. It is expected that this review can offer insights into features of CSCs and the exploration of targeting nanodrug delivery systems.

Keywords: Cancer stem cells; Cancer therapy; Drug delivery system; Nanomedicine.

Fig. 1

Possible therapies and strategies that can eliminate CSCs

Fig. 2

Chemical structures of several compounds targeting Wnt and Notch signaling pathways of CSCs

Fig. 3

Anti-ALDH and Sialic acid co-modified PLGA nanoparticles for targeting brain CSCs. Adapted from [60]

Fig. 4

Mesoporous silica nanoparticles co-loaded cisplatin and HNF4α DNA plasmid to reduce the portion of liver CSCs. Adapted from [63]

Fig. 5

Different types of photothermal agents used for PTT

Fig. 6

Combination of PTT with other antitumor therapies. Photodynamic therapy (PDT), Chemotherapy (CT), Immunotherapy (IT)

Fig. 7

Schematic illustration of exosome-sheathed porous silicon nanoparticles (PSiNPs) as nano-carriers for CSCs targeting delivery. Permission by Creative Commons CC BY [93]

Fig. 8

Schematic illustration of nanodiscs against ALDH^high CSCs. Adapted from [98]