Cancer stem cells and nanomedicine: new opportunities to combat multidrug resistance?

Dalpiaz, Alessandro; Paganetto, Guglielmo; Botti, Giada; Pavan, Barbara

doi:10.1016/j.drudis.2020.07.023

Cited by 22 publications

(24 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Elevated expression of ATP-binding cassette (ABC) pumps and detoxifying enzymes to increase the drug’s efflux, which is considered to be an important mechanism for multi-drug resistance (MDR). Multi-drug resistance is either intrinsic and present before the start of treatment or acquired after exposure to treatment [ 25 ]. …”

Section: Cancer Stem Cell Biologymentioning

confidence: 99%

“…The niche is an intrinsically dynamic system formed by the tumor microenvironment, with specific anatomical and functional features to maintain the CSCs [ 17 ]. A common feature of different tumors is hypoxia, which results from the abnormal growth of cancer cells and aberrant angiogenesis [ 25 , 27 ]. The nutrient deficiency created by aberrant cell growth instructs CSCs to activate the autophagy process, namely, type II programmed cell death, to restore the ATP energy level required for the metabolism of other cells [ 12 ].…”

Section: Cancer Stem Cell Biologymentioning

confidence: 99%

See 1 more Smart Citation

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

et al. 2021

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs. This review covers the biology of CSCs and advances in the design and synthesis of NPs as a carrier in targeting cancer drugs to the CSC subpopulation of cancer cells. This review includes the development of synthetic and natural polymeric NPs, lipid NPs, inorganic NPs, self-assembling protein NPs, antibody-drug conjugates, and extracellular nanovesicles for CSC targeting.

show abstract

Section: Cancer Stem Cell Biologymentioning

confidence: 99%

Section: Cancer Stem Cell Biologymentioning

confidence: 99%

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This difficulty can be overcome by coating the nanoparticle surfaces with hydrophilic polymers, such as polyethylene glycol (PEG), able to repel the absorption of opsonin proteins. This strategy allows prolonging the circulation times in the bloodstream of the nanoparticles by several orders of magnitude, such that these nanoparticles are named “stealth” nanoparticles [ 22 , 81 ].…”

Section: The Use Of Nanoparticulate Systems For Drug Delivery Into the Brainmentioning

confidence: 99%

“…In particular, the inhibitory effect on temozolomide-resistant glioblastoma multiforme in orthotopic glioblastoma mice models was attributed to CAT3 following its oral administration [ 102 ]. This effect could be mainly exerted on cancer stem cells that normally lead to recurrent disease and MDR associated with tumors [ 81 ]. CAT3 is a class IV drug in the biopharmaceutics classification system, insoluble in water and with scarce lipid solubility, showing very poor bioavailability following oral administration.…”

Section: The Use Of Nanoparticulate Systems For Drug Delivery Into the Brainmentioning

confidence: 99%

“…Moreover, the drug loading of self-assembled nanoparticles was very high when compared to traditional nanoparticulate systems, the prodrug itself being the unique component of the nanostructures. The system was designed to reach the tumoral tissues by passive targeting through the enhanced permeability and retention (EPR) phenomenon, which is essentially due to large spaces between endothelial cells of tumor vessels and impaired lymphatic drainage caused by compression of intratumor lymphatic vessels [ 81 ]. Interestingly, CPT-ss-triazole-GEM nanoparticles showed a higher cytotoxicity against HepG2 cells when compared to not self-assembled CPT and GEM [ 116 ].…”

Section: The Use Of Nanoparticulate Systems For Drug Delivery Into the Brainmentioning

confidence: 99%

See 1 more Smart Citation

Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration

2021

Self Cite

View full text Add to dashboard Cite

About 40 years ago the lipidization of hydrophilic drugs was proposed to induce their brain targeting by transforming them into lipophilic prodrugs. Unfortunately, lipidization often transforms a hydrophilic neuroactive agent into an active efflux transporter (AET) substrate, with consequent rejection from the brain after permeation across the blood brain barrier (BBB). Currently, the prodrug approach has greatly evolved in comparison to lipidization. This review describes the evolution of the prodrug approach for brain targeting considering the design of prodrugs as active influx substrates or molecules able to inhibit or elude AETs. Moreover, the prodrug approach appears strategic in optimization of the encapsulation of neuroactive drugs in nanoparticulate systems that can be designed to induce their receptor-mediated transport (RMT) across the BBB by appropriate decorations on their surface. Nasal administration is described as a valuable alternative to obtain the brain targeting of drugs, evidencing that the prodrug approach can allow the optimization of micro or nanoparticulate nasal formulations of neuroactive agents in order to obtain this goal. Furthermore, nasal administration is also proposed for prodrugs characterized by peripheral instability but potentially able to induce their targeting inside cells of the brain.

show abstract

Nitric Oxide‐Based Nanomedicines for Conquering TME Fortress: Say “NO” to Insufficient Tumor Treatment

Xiang,

Chen,

Nan

et al. 2023

Adv Funct Materials

View full text Add to dashboard Cite

Almost all cancer treatments are significantly limited by the strong tumor microenvironment (TME) fortress formed by abnormal vasculature, dense extracellular matrix (ECM), multidrug resistance (MDR) system, and immune “cold” environment. In the huge efforts of dismantling the TME fortress, nitric oxide (NO)‐based nanomedicines are increasingly occupying a central position and have already been identified as super “strong polygonal warriors” to dismantle TME fortress for efficient cancer treatment, benefiting from NO's unique physicochemical properties and extremely fascinating biological effects. However, there is a paucity of systematic review to elaborate on the progress and fundamental mechanism of NO‐based nanomedicines in oncology from this aspect. Herein, the key characteristics of TME fortress and the potential of NO in reprogramming TME are delineated and highlighted. The evolution of NO donors and the advantages of NO‐based nanomedicines are discussed subsequently. Moreover, the latest progress of NO‐based nanomedicines for solid tumors is comprehensively reviewed, including normalizing tumor vasculature, overcoming ECM barrier, reversing MDR, and reactivating the immunosuppression TME. Lastly, the prospects, limitations, and future directions on NO‐based nanomedicines for TME manipulation are discussed to provide new insights into the construction of more applicable anticancer nanomedicines.

show abstract

Cancer stem cells and nanomedicine: new opportunities to combat multidrug resistance?

Cited by 22 publications

References 137 publications

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

Targeting Systems to the Brain Obtained by Merging Prodrugs, Nanoparticles, and Nasal Administration

Nitric Oxide‐Based Nanomedicines for Conquering TME Fortress: Say “NO” to Insufficient Tumor Treatment

Contact Info

Product

Resources

About