Nano-engineered mesenchymal stem cells as targeted therapeutic carriers

Sadhukha, Tanmoy; O’Brien, Timothy; Prabha, Swayam

doi:10.1016/j.jconrel.2014.10.015

Cited by 97 publications

(115 citation statements)

References 39 publications

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“…These results are in agreement with previous studies using MSCs and nanoparticles. 80,81 In vivo migration results with SCID mice revealed that most MSCs were located in tumor tissue in comparison to healthy organs and MSC injection site. The highest number of MSCs was detected in the tumor 24 h postinjection, suggesting that short periods are sufficient and most suitable for MSCs to reach the tumor.…”

mentioning

confidence: 99%

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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Purpose Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs). Materials and methods Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used. Results QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver). Conclusion Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy.

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mentioning

confidence: 99%

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dapkutė¹,

Steponkienė²,

Bulotienė³

et al. 2017

IJN

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“…Instead, the most exciting and clinically relevant finding is that MSCs possess unique tumor-trophic, drug-resistant and migratory properties and overexpress efflux transporters such as P-glycoproteins [125]. These features have founded the rationale to develop MSCs as vehicles to deliver specific anti-angiogenic and anti-tumor agents [127,128]. These genetically engineered MSCs can successfully deliver an antagonist of the hepatocyte growth factor, the TNF-related apoptosis-inducing ligand (TRAIL) and IFN-a with potent anti-tumor effects both in vitro and in vivo [128][129][130].…”

Section: Potential Targetsmentioning

confidence: 99%

Therapeutically targeting SELF‐reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?

et al. 2016

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A tight relationship between the acute myeloid leukemia (AML) population and the bone marrow (BM) microenvironment has been convincingly established. The AML clone contains leukemic stem cells (LSCs) that compete with normal hematopoietic stem cells (HSCs) for niche occupancy and remodel the niche; whereas, the BM microenvironment might promote AML development and progression not only through hypoxia and homing/adhesion molecules, but also through genetic defects. Although it is still unknown whether the niche influences treatment results or contains any potential target for treatment, this dynamic AML-niche interaction might be a promising therapeutic objective to significantly improve the AML cure rate.

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“…Furthermore, stem cells are highly resistant to anticancer drugs compared with normal and cancer cells. 7,8 However, excessive dosing with unrationalized drug design will eventually degrade the functions of stem cells and induce unexpected side effects (such as unexpected orphan diseases).…”

Section: Introductionmentioning

confidence: 99%

“…This study examined hMSC uptake of biocompatible polymer-based NP (PLGA) (rather than conjugated NP on the extracellular membrane), but did not observe any alteration in MSC viability, differentiation, or migration ability. 7 Cytotoxic drug (eg, paclitaxel) showed poor intracellular accumulation in hMSCs because MSCs have active drug efflux transporters, such as P-glycoprotein. Selective accumulation of hMSCs (with polymeric NP uptake) in the lungs was observed, while free polymer NPs (without hMSCs) mainly accumulated in the liver and spleen (Figure 3).…”

mentioning

confidence: 99%

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Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

Kim¹,

Khang²

2015

IJN

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Over the past 60 years, numerous medical strategies have been employed to overcome neoplasms. In fact, with the exception of lung, bronchial, and pancreatic cancers, the 5-year survival rate of most cancers currently exceeds 70%. However, the quality of life of patients during chemotherapy remains unsatisfactory despite the increase in survival rate. The side effects of current chemotherapies stem from poor target efficiency at tumor sites due to the uncontrolled biodistribution of anticancer agents (ie, conventional or current approved nanodrugs). This review discusses the effective physiochemical factors for determining biodistribution of nanocarriers and, ultimately, increasing tumor-targeting probability by avoiding the reticuloendothelial system. Second, stem cell-conjugated nanotherapeutics was addressed to maximize the tumor searching ability and to inhibit tumor growth. Lastly, physicochemical material properties of anticancer nanodrugs were discussed for targeting cellular organelles with modulation of drug-release time. A better understanding of suggested topics will increase the tumor-targeting ability of anticancer drugs and, ultimately, promote the quality of life of cancer patients during chemotherapy.

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Nano-engineered mesenchymal stem cells as targeted therapeutic carriers

Cited by 97 publications

References 39 publications

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Therapeutically targeting SELF‐reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?

Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

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