Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Abstract

Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

Enhancing cancer therapy: the integration of oncolytic virus therapy with diverse treatments

“…Developing novel delivery systems to enhance the stability and delivery efficiency of oncolytic virus is another crucial research area. For instance, employing nanotechnology and biomaterials [ 69 , 72 ] can help improve the persistence and targeting of viruses in the body, leading to more effective treatments [ 78 , 79 ]. Additionally, exploring combination therapies that integrate oncolytic virus with immunotherapies, targeted therapies, or radiotherapy could yield synergistic effects, thereby improving overall treatment outcomes.…”

The investigation of oncolytic viruses in the field of cancer therapy

“…MSCs possess low immunogenicity, inherent tumor tropism, multi-lineage differentiation potential, excellent migratory capacity ( 147 ), homing ability, and other therapeutic properties. These innate characteristics make them ideal candidates for drug delivery and OV vectors ( 148 , 149 ). Utilizing MSCs as carriers of OVs for tumor therapy can enhance viral delivery efficiency, augment the antitumor effect of viruses on cancer cells, enable precise drug targeting, and mitigate systemic side effects ( 150 ).…”

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

“…Notwithstanding, several strategies are currently being developed to use MSCs as anti-cancer cell therapeutics. These include bioengineering MSCs to enhance their tumour homing and anti-tumour properties, or to carry as a "Trojan horse" some therapeutic agents that target and eliminate cancer cells more efficiently [24][25][26][27][28]. The development of such strategies requires a deep understanding of the interactions between MSCs, tumour microenvironment and immune system and calls for an interdisciplinary approach combining insights from cell biology, oncology and cell bioengineering to overcome current challenges and fully exploit the therapeutic potential of MSCs in cancer treatment.…”