The Implications and Future Perspectives of Nanomedicine for Cancer Stem Cell Targeted Therapies

Abstract

Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs. In recent years, many reports have shown the use of CSCs-specific approaches such as ATP-binding cassette (ABC) transporters, blockade of self-renewal and survival of CSCs, CSCs surface markers targeted drugs delivery and eradication of the tumor microenvironment. Also, various therapeutic agents such as small molecule drugs, nucleic acids, and antibodies are said to destroy CSCs selectively. Targeted drug delivery holds the key to the success of most of the anti-CSCs based drugs/therapies. The convention CSCs-specific therapeutic agents, suffer from various problems. For instance, limited water solubility, small circulation time and inconsistent stability of conventional therapeutic agents have significantly limited their efficacy. Recent advancement in the drug delivery technology has demonstrated that specially designed nanocarrier-based drug delivery approaches (nanomedicine) can be useful in delivering sufficient amount of drug molecules even in the most interiors of CSCs niches and thus can overcome the limitations associated with the conventional free drug delivery methods. The nanomedicine has also been promising in designing effective therapeutic regime against pump-mediated drug resistance (ATP-driven) and reduces detrimental effects on normal stem cells. Here we focus on the biological processes regulating CSCs' drug resistance and various strategies developed so far to deal with them. We also review the various nanomedicine approaches developed so far to overcome these CSCs related issues and their future perspectives.

Keywords: CSCs; autophagy; drug resistance of CSC; immunotherapy of cancer; nanocarrier; nanomedicine; tumor suppressor protein p53.

Figure 1

Illustration of various anti-CSCs modalities to cure different types of cancers. There have been accumulating study and clinical report about the various mechanism for targeting CSCs and other cancer cells as indicated above. Various research/clinicians have also demonstrated different molecules or strategies with variable efficiencies.

Figure 2

Various roles of CSCs in tumor progression. There are different types of roles which CSCs might play in tumor progression and cause them to become resistant to the most of the conventional therapeutic modalities. Tumor progression: The inherent properties of CSCs to self-renew, proliferate, and differentiation makes them eligible to support tumor progression. Drug resistance: the abilities of CSCs to survive against various cytotoxic insults including chemotherapy/radiotherapy through different mechanism may cause the accumulation of them resulting in enrichment of CSCs within tumors making it harder to cure cancers. Metastasis onset: Acquisition of mesenchymal cell-like features by CSCs it impossible that tumor cell starts migrating to the local and distant locations causing the onset of metastases. Relapse: the remaining CSCs that may survive the anti-tumor treatment remedy can increase their population by proliferating and may result to the relapse after an initial therapeutic success.

Figure 3

Illustration of various types of nanoparticles being explored for their efficiency to carry desired anti-CSCs/anti-cancer drug molecules. These nanocarriers are often equipped with targeting moieties, e.g., antibodies, antigen, etc. the different types of nanoparticles are developed from many types of biomaterial, e.g., lipids, metals, carbon, polymeric substances, etc. Acknowledgment: The various nanoparticles SEM/TEM figures are taken from the previously published work with prior permission/OR accessible under open access. Carbon Nanotubes: Eatemadi et al. (2014) (Open Access). Dendrimers: Abd-El-Aziz et al. (2016) (Permission granted by author). Liposomal: Lim et al. (2013) (Permission granted by author). Hybrid solid-liquid particles: Patel et al. (2016) (Open access). Polymeric particles: Halayqa and Domańska (2014) (Open Access). Metal nanoparticles: Raj and Jayalakshmy (2015).