MSCs as Tumor-Specific Vectors for the Delivery of Anticancer Agents—A Potential Therapeutic Strategy in Cancer Diseases: Perspectives for Quinazoline Derivatives

Abstract

Mesenchymal stem cells (MSCs) are considered to be a powerful tool in the treatment of various diseases. Scientists are particularly interested in the possibility of using MSCs in cancer therapy. The research carried out so far has shown that MSCs possess both potential pro-oncogenic and anti-oncogenic properties. It has been confirmed that MSCs can regulate tumor cell growth through a paracrine mechanism, and molecules secreted by MSCs can promote or block a variety of signaling pathways. These findings may be crucial in the development of new MSC-based cell therapeutic strategies. The abilities of MSCs such as tumor tropism, deep migration and immune evasion have evoked considerable interest in their use as tumor-specific vectors for small-molecule anticancer agents. Studies have shown that MSCs can be successfully loaded with chemotherapeutic drugs such as gemcitabine and paclitaxel, and can release them at the site of primary and metastatic neoplasms. The inhibitory effect of MSCs loaded with anti-cancer agents on the proliferation of cancer cells has also been observed. However, not all known chemotherapeutic agents can be used in this approach, mainly due to their cytotoxicity towards MSCs and insufficient loading and release capacity. Quinazoline derivatives appear to be an attractive choice for this therapeutic solution due to their biological and pharmacological properties. There are several quinazolines that have been approved for clinical use as anticancer drugs by the US Food and Drug Administration (FDA). It gives hope that the synthesis of new quinazoline derivatives and the development of methods of their application may contribute to the establishment of highly effective therapies for oncological patients. However, a deeper understanding of interactions between MSCs and tumor cells, and the exploration of the possibilities of using quinazoline derivatives in MSC-based therapy is necessary to achieve this goal. The aim of this review is to discuss the prospects for using MSC-based cell therapy in cancer treatment and the potential use of quinazolines in this procedure.

Incorporating Cryopreservation Evaluations Into the Design of Cell-Based Drug Delivery Systems: An Opinion Paper

“…Conventional chemotherapy are still limited by some factors including poor pharmacokinetics, accumulation in noncancerous tissues, and toxicity (18). Stem cells are applicable in overcoming these limitations as they can be engineered and used as carriers or vehicles for targeted drug delivery based on the proposition that mesenchymal stem cells (MSCs) undergo chemotaxis toward tumors following the release of chemoattractants like vascular endothelial growth factor (VEGF) (19). Gao et al showed that MSCs are promising in this regard as the stem cells carrying paclitaxel loaded nanoparticles (NPs) were able to deliver their therapeutic pay-load to murine orthotopic glioma cells (20).…”

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

“…MSCs have some interesting properties, such as their ability to selectively migrate to local and distant tumoral sites and penetrate the tumor stroma after intravenous injection, as demonstrated in pancreas, melanoma, lung, or breast cancer animal models [86][87][88]. As a vehicle, MSCs may deliver drugs, genes, or other therapeutic agents such as cytokines in various cancers, promoting therapeutic properties, comprising anti-tumor, -proliferative, -inflammatory, -oxidative, or -metastatic effects [240,241]. Numerous studies enumerate the potential benefic effects of MSCs transduced/transfected with viral/non-viral constructs involving the overexpression of therapeutic agents [241][242][243].…”

Design, synthesis, in-silico studies and apoptotic activity of novel amide enriched 2-(1H)- quinazolinone derivatives

“…Quinazoline and quinazolinone derivatives have been attracted by biologists and medicinal chemists due to their diverse pharmacological activities [ 19 , 20 ], including anticancer [ [21] , [22] , [23] , [24] ], antitubercular [ [25] , [26] , [27] ], antimalarial [ 28 ], anti-inflammatory [ 29 , 30 ], antimicrobial [ 31 ], anticonvulsant [ 32 ], antihypertensive [ 33 , 34 ], antidiabetic [ 35 ], anti-HIV [ 36 ], antitumor [ [37] , [38] , [39] ], antioxidant [ 40 ], antiviral [ 41 ], kinase inhibitory [ 42 ], sedative-hypnotic, antihistaminic and many other uses [ 43 ]. Quinazoline and its derivatives are promising cancer chemotherapeutic agents for treating solid tumors [ [44] , [45] , [46] , [47] , [48] , [49] , [50] ]. The FDA has approved many quinazoline derivatives for clinical use as cancer treatments.…”