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Owing to their characteristic structures, metal-organic frameworks (MOFs) are considered as the leading candidate for drug-delivery materials. However, controlling the synthesis of MOFs with uniform morphology and high drug-loading/release efficiencies is still challenging, which greatly limits their applications and promotion. Herein, a multifunctional MOF-based drug-delivery system (DDS) with a controlled pore size of 100-200 nm for both therapeutic and bioimaging purposes was successfully synthesized in one step. Fe-MOF-based microcapsules were synthesized through a competitive coordination method, which was profited from the intrinsic coordination characteristics of the Fe element and the host-guest supramolecular interactions between Fe3+ and polyoxometalates anions. This as-synthesized macroporous DDS could greatly increase the drug-loading/release rate (77%; 83%) and serve as a magnetic resonance (MR) contrast agent. Because an Fe-containing macroporous DDS presents ultrahigh drug loading/release, the obtained 5-FU/Fe-MOF-based microcapsules displayed good biocompatibility, extremely powerful inhibition of tumor growth, and satisfactory MR imaging capability. Given all these advantages, this study integrates high therapeutic effect and diagnostic capability via a simple and effective morphology-controlling strategy, aiming at further facilitating the applications of MOFs in multifunctional drug delivery.

The bioactive lipid sphingosine 1-phosphate (S1P) is implicated in many pivotal processes for the physiological and pathological actions via activating five types of G-protein-coupled S1P receptors (S1PR1-5). The role of S1P in renal cell carcinoma (RCC) and its receptor subtype specific mediating mechanism are poorly studied. So we focus on the regulatory role of S1P in RCC progression and the receptor subtypes involved in S1P-induced actions, intending to further clarify a novel therapeutic target for RCC. Analysis of The Cancer Genome Atlas (TCGA) databases showed that the patients with high expression of S1PR3 had significantly worse overall than with low expression. We further demonstrated that S1P could promote proliferation, migration, and epithelial-mesenchymal transition (EMT) of renal cancer cells in vitro, and the actions were enhanced with the increase of S1PR3 expression. Meanwhile, the results in animal experiments also showed that S1PR3 could accelerate tumorigenesis and metastasis of RCC. Our study also clarified the mechanism for S1P induced cell proliferation is mediated by S1PR3/Gi/p38/Akt/p65/cyclin D1-CDK4 pathway and the main pathway for migration is S1PR3/Gi/q/ERK/p38/p65. In addition, S1PR3 was involved in epidermal growth factor (EGF)-induced actions by enhancing protein expression, not by transactivation of epidermal growth factor receptor (EGFR). These results also further supported our conclusion that the carcinogenic role of S1P/S1PR3 axis. Thus, our findings provide that S1PR3 may be a promising small molecular therapeutic target for S1PR3 expressed cancers.

Lysophosphatidic acid (LPA), as a bioactive lipid, plays a variety of physiological and pathological roles via activating six types of G-protein-coupled LPA receptors (LPA1–6). Our preliminary study found that LPA1 is highly expressed in lung cancer tissues compared with paracancerous tissues, but the role of LPA1 in lung carcinoma is unclear. This study aimed to elucidate the association between LPA1 and lung tumour behaviour at the cellular and animal model levels. We found that LPA promoted the migration, proliferation and colony formation of a lung cancer cell line (A549). LPA1 and LPA3 are preferentially expressed in A549 cells, and both Ki16425 (LPA1 and LPA3 antagonist) and ono7300243 (LPA1 antagonist) completely blocked the LPA-induced actions. These results were further verified by experiments of the LPA1/3 overexpression and LPA1 knockdown A549 cells. Furthermore, LPA1 overexpression and knockdown A549 cells were used to assess the in vivo tumour-bearing animal model and the mechanism underlying LPA-induced actions. In the animal model, A549 cell-derived tumour volume was significantly increased by LPA1 overexpression and significantly decreased by LPA1 knockdown respectively, suggesting that LPA1 is a regulator of in vivo tumour formation. Our results also indicated that the LPA1/Gi/MAP kinase/NF-κB pathway is involved in LPA-induced oncogenic actions in A549 cells. Thus, targeting LPA1 may be a novel strategy for treating lung carcinoma.