Mesenchymal stem cell (MSC) based therapy holds great potential for treating numerous diseases owing to their capability to heal injured tissue/organs through paracrine factors secretion and immunomodulation. Despite the high hopes, the low viability of transplanted cells in the injured tissues due to the elevated oxidative stress levels remains the largest obstacle in MSC-based cell therapy. To achieve desired therapeutic efficiency, the survival of the transplanted MSCs in the high oxidative stress environment needs to be ensured. Herein, we proposed the use of a ROS-scavenging nanozyme to protect transplanted MSCs from oxidative stress-mediated apoptosis and thereby improve the therapeutic effect. Prussian blue (PB) nanoparticles as a biocompatible ROS-scavenging nanozyme were incorporated into the MSCs without affecting the stemness and differentiation potential of MSCs. The nanozyme impregnation significantly improved the survival of MSCs in a high oxidative stress condition as well as augmented their paracrine effect and anti-inflammatory properties, resulting in a profound therapeutic effect in vivo in the liver ischemia-reperfusion (I/R) injury animal model. Our results indicated that the nanozyme incorporation into MSCs is a simple but efficient way to improve the therapeutic potential of MSC-based cell therapy.

Nanozyme Impregnated Mesenchymal Stem Cells for Hepatic Ischemia-Reperfusion Injury Alleviation.

Current advances and challenges of mesenchymal stem cells-based drug delivery system and their improvements.

Cell-based drug delivery systems have shown tremendous advantages in cancer treatment due to their distinctive properties. For instance, delivery of therapeutics using tumor-tropic cells like neutrophils, lymphocytes and mesenchymal stem cells can achieve specific tumor targeting due to the "Trojan Horse" effect. Other circulatory cells like erythrocytes and platelets can greatly improve the circulation time of nanoparticles due to their innate long circulation property. Adipocytes, especially cancer-associated adipocytes, play key roles in tumor development and metabolism, therefore, adipocytes are regarded as promising bio-derived nanoplatforms for anticancer targeted drug delivery. Nanomaterials are important participants in cell-based drug delivery because of their unique physicochemical characteristics. Therefore, the integration of various nanomaterials with different cell types will endow the constructed delivery systems with many attractive properties due to the merits of both. In this review, a number of strategies based on nanomaterial-involved cell-mediated drug delivery systems for cancer treatment will be summarized. This review discusses how nanomaterials can be a benefit to cell-based therapies and how cell-derived carriers overcome the limitations of nanomaterials, which highlights recent advancements and specific biomedical applications based on nanomaterial-mediated, cell-based drug delivery systems.

Combination of Nanomaterials in Cell-Based Drug Delivery Systems for Cancer Treatment.

Introduction Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene- or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

https://www.tandfonline.com/doi/pdf/10.1080/17425247.2021.1960309

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Targeted drug and gene delivery is the key for precision therapy. Lipid nanoparticles as non-viral vectors have attracted extensive attentions in treating a variety of diseases, such as cancer, immune disease, cardiac diseases and pathogen infection. They exhibit low immunogenicity and low cytotoxicity, which make them as the most-commonly used vectors. More importantly, their surfaces could be functionalized, which provide a platform to improve targeting and pharmacokinetic/pharmacodynamic properties. Although there has been great success to synthesize lipid nanoparticles, it remains as a challenge to produce active targeting lipid nanoparticles especially with definable targetability, high quality and good translation reproducibility. This review focus on the techniques to fabricate active targeting lipid nanoparticles. We start with a brief introduction of targeting lipid nanoparticles, followed by a focused discussion of various preparation approaches including one-pot assembly and post-insertion functionalization. The methods, mechanism and representative examples are introduced, together with the comparison of their advantages and restrictions. Finally, challenges facing formulation screening and clinical translation are discussed. • Active targeting lipid nanoparticle is a clinical-available platform for precision nanomedicine. • One-pot assembly strategy allows for feasible fabrication and modulation of targeting ligand density. • Post-insertion strategy makes it possible to conjugate antibodies and other fragile targeting ligands. • Challenges facing clinical translations of active targeting lipid nanoparticles exist. 

Ikumi Kiyama

Papers

Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy.