Engineering exosomes as refined biological nanoplatforms for drug delivery

Luan, Xin; Sansanaphongpricha, Kanokwan; Myers, Ila; Chen, Hongwei; Yuan, Hebao; Sun, Duxin

doi:10.1038/aps.2017.12

Cited by 805 publications

(688 citation statements)

References 72 publications

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“…drugs, proteins, RNA, etc.) into targeted MSC‐derived extracellular vesicles or exosomes via active or passive loading mechanisms . Despite these approaches, lung entrapment remains a critical challenge for MSC‐based drug delivery; although evidence suggests this is a surmountable engineering challenge.…”

Section: Msc Homing Mechanismsmentioning

confidence: 99%

“…A significant limitation for many of these strategies has been the lack of robust MSC homing to target tissues . It has been posited that MSCs primarily ‘act at a distance’ via exosomes, polarization of phagocytic monocytes, and other paracrine effects , which may partially overcome poor targeting and broad biodistribution of systemically infused MSCs, particularly when coupled with exosome targeting strategies . However, increased activity directly in target tissue would likely be of significant benefit for many applications, especially for those using MSCs as cell‐based drug delivery vectors; wherein limiting toxicity to peripheral nontarget tissues is of critical importance.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

Krueger

Thorek

Denmeade

et al. 2018

Stem Cells Translational Medicine

195

135

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The development of mesenchymal stem cells (MSCs) as cell‐based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor‐selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i.e., the good). Unfortunately, the lack of robust quantification and widespread adoption of standardized methodologies with high sensitivity and resolution has made accurate comparisons across studies difficult, which has significantly impeded progress (i.e., the ugly). Herein, we provide a concise review of active and passive MSC homing mechanisms and biodistribution postinfusion; in addition to in vivo cell tracking methodologies and strategies to enhance tumor targeting with a focus on MSC‐based drug delivery strategies for cancer therapy. Stem Cells Translational Medicine 2018;1–13

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Section: Msc Homing Mechanismsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

Krueger

Thorek

Denmeade

et al. 2018

Stem Cells Translational Medicine

195

135

View full text Add to dashboard Cite

show abstract

“…Exosomes, a kind of vesicle excreted by normal cells, were engineered to carry KRAS siRNA for the treatment of pancreatic cancer . The naturally expressed proteins (e.g., CD47) on the membrane protected the exosomes from phagocytosis by the monocytes and macrophages . However, biomimetic nanomedicine is still in its early development stage and far from clinical translation.…”

Section: Strategies To Reduce Np Uptake By the Mpsmentioning

confidence: 99%

New Strategies in the Design of Nanomedicines to Oppose Uptake by the Mononuclear Phagocyte System and Enhance Cancer Therapeutic Efficacy

Zhou

Dai

2018

Chemistry An Asian Journal

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The application of nanotechnology in the treatment of tumors has boomed owing to the vigorous development in cancer nanomedicine. Despite the great success achieved in this field, nanomedicine has not realized its full potential owing to a delivery barrier, the mononuclear phagocytic system (MPS), which cuts off more than 95 % of the administrated nanoparticles. This results in an extremely low drug-delivery efficacy to the tumor and leads to poor therapeutic outcomes. Moreover, the injection of excess nanoparticles also raises toxicity concerns induced by the accumulation of nanomaterials in organs, such as the liver and spleen. Therefore, a reduction in the uptake of nanomedicines by the MPS is vital to enhance the cancer therapeutic effect and decrease side effects. In this critical review, we will summarize the new strategies to reduce nanoparticle uptake by the MPS based on current knowledge of the bio-nano interaction. Further directions will also be highlighted for the development of cancer nanomedicine with a lower off-target rate and better therapeutic outcomes.

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“…In the past decade, stem cell‐derived exosomes have gained great importance in regenerative medicine and have exhibited promise for clinical translation. However, one major problem for stem cell‐derived exosome therapies is identifying appropriate source cells .…”

Section: Introductionmentioning

confidence: 99%

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

Zhu

Jia

Wang

et al. 2019

Stem Cells Translational Medicine

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Stem cell‐derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell‐derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC‐exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC‐exos). BMSCs were isolated from rats with streptozotocin‐induced diabetes and normal rats. dBMSC‐exos and nBMSC‐exos were isolated by an ultracentrifugation method and identified. The effects of dBMSC‐exos and nBMSC‐exos on the proliferation and migration of BMSCs and human umbilical vein endothelial cells (HUVECs) were investigated. The effects of exosomes on the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs were compared. Finally, a rat calvarial defect model was used to compare the effects of exosomes on bone regeneration and neovascularization in vivo. In vitro, dBMSC‐exos and nBMSC‐exos both enhanced the osteogenic differentiation of BMSCs and promoted the angiogenic activity of HUVECs, but nBMSC‐exos had a greater effect than dBMSC‐exos. Similarly, in vivo, both dBMSC‐exos and nBMSC‐exos promoted bone regeneration and neovascularization in rat calvarial defects, but the therapeutic effect of nBMSC‐exos was superior to that of dBMSC‐exos. The present study demonstrates for the first time that the bone regenerative effect of exosomes derived from BMSCs is impaired in type 1 diabetes, indicating that for patients with type 1 diabetes, the autologous transplantation of BMSC‐exos to promote bone regeneration may be inappropriate. stem cells translational medicine 2019;8:593–605

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Engineering exosomes as refined biological nanoplatforms for drug delivery

Cited by 805 publications

References 72 publications

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise

New Strategies in the Design of Nanomedicines to Oppose Uptake by the Mononuclear Phagocyte System and Enhance Cancer Therapeutic Efficacy

Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes

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