Background: Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment. Purpose: The 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. Methods: Ptx-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. Results: The 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. Conclusion: Based 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.

Mesenchymal stem cell (MSC)-based biomimetic delivery has been actively explored for drug accumulation and penetration into tumors by taking advantage of the tumor-tropic and penetration properties of MSCs. In this work, we further demonstrated the feasibility of MSC-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport via an endocytosis–exocytosis–endocytosis process between MSCs and cancer cells. Chlorin e6 (Ce6)-conjugated polydopamine nanoparticles (PDA-Ce6) were developed and loaded into the MSCs. Phototherapeutic agents are safe to the MSCs, and their very low dark toxicity causes no impairment of the inherent properties of MSCs, including tumor-homing ability. The MSCs loaded with PDA-Ce6 (MSC-PDA-Ce6) were able to target and penetrate into tumors and exocytose 60% of the payloads in 72 h. The released PDA-Ce6 NPs could penetrate deep and be re-endocytosed by the cancer cells. MSC-PDA-Ce6 tended to accumulate in the lungs and delivered PDA-Ce6 into the tumors after intravenous injection in the mouse model with lung melanoma metastasis. Phototoxicity can be selectively triggered in the tumors by sequentially treating with near-infrared irradiation to induce photodynamic therapy (PDT) and photothermal therapy (PTT). The MSC-based biomimetic delivery of PDA-Ce6 nanoparticles is a potential method for dual phototherapy against lung melanoma metastasis.

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.

A systematic study showcasing a library of multi-component gels using the novel gelator C14-FF and various biocomponents for the development of tuneable matrices.

Cryptotanshinone (CTS) is a plant product extracted from Salvia miltiorrhiza Bunge with various pharmacological significances. In addition to its activities against coronary heart disease, hyperlipidemia, stroke, hepatitis and chronic renal failure, it demonstrates antimetastatic effects. However, its clinical use is limited due to its poor aqueous solubility and oral bioavailability. Herein, CTS nanocrystals were prepared with the precipitation method followed by high-pressure homogenization using Poloxamer 407 as the stabilizer. A stable product was further obtained by lyophilization. The particle size of the CTS nanocrystals was 315.67 ± 11.02 nm, and the zeta potential was near 0 mV. The crystallinity was confirmed by DSC and PXRD. The saturation solubility was substantially increased from 0.97 ± 0.12 μg/ml to 62.29 ± 1.91 μg/ml, and the dissolution rate was also significantly accelerated. A pharmacokinetic study in rats revealed an improvement in oral bioavailability (2.87-fold) with CTS nanocrystals compared to the raw drug. In conclusion, the results of this study suggest a feasible formulation for the oral delivery of CTS.