BackgroundMesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.PurposeThe objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.MethodsPtx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.ResultsThe optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.ConclusionBased on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

A cell-based biomimetic delivery system characterized by its “Trojan horse” property is developed, in which the PDA-Ce6 nanoparticles were loaded in the MSCs for tumor-targeted delivery and combination PDT/PTT for retarding lung melanoma metastasis.

Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development.

Aim: A photomedicine consisting of a core for photothermal therapy, a photosensitizer for photodynamic therapy, and a cancer-targeting moiety was fabricated to improve photosensitizer selectivity and antitumor efficiency. Materials & methods: Hyaluronic acid-decorated polydopamine nanoparticles with conjugated chlorin e6 (HA–PDA–Ce6) were synthesized and characterized. Cell uptake, phototoxicity, penetration, distribution and therapeutic effects were evaluated. Results: HA–PDA–Ce6 had high photoactivities for photodynamic therapy/photothermal therapy and was readily internalized via CD44-mediated endocytosis. Enhanced accumulation and deeper penetration into tumors were achieved by the diffusion molecular retention tumor targeting effect following peritumoral injection. In the combination therapy, HA–PDA–Ce6 displayed the highest tumor growth inhibition in HCT-116 tumor-bearing mice. Conclusion: HA–PDA–Ce6 is promising for targeted colorectal cancer therapy.

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Correction for ‘A Trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy against lung melanoma metastasis’ by Xumei Ouyang et al., Biomater. Sci., 2020, DOI: 10.1039/c9bm01401b.

To simplify the preparation of dendritic materials, host–guest molecular recognition and self‐assembly are utilized to form a supramolecular dendritic gene vector (DNCVP). DNCVP is constructed from an amino dendron‐conjugated naphthol, viologen containing pH‐sensitive hydrazone‐bond‐linked PEG, and CB[8] with a molar ratio of 1:1:1. The pH‐ and reducing‐sensitivity of DNCVP is verified, and the stimuli‐responsive capacity enables the vector tumor targeting gene delivery ability. Owing to the protection of surface PEG, the supramolecular engineering endows the delivery vector with low cytotoxicity and good biocompatibility that are confirmed by the MTT assay. The excellent delivery ability of genes is investigated by in vitro transfection of pEGFP, pGL3, and silencing of siGAPDH. In vivo studies demonstrate promoted tumor accumulation of genes mediated by the dual‐responsive DNCVP and the transfection efficiency at the tumor site is greatly improved benefiting from the dynamic nature of noncovalent interactions. This study reveals DNCVP is a promising supramolecular dendritic gene delivery vector, providing a sophisticated strategy for precise gene therapy.