Asprin-loaded strontium-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite promotes regeneration of critical bone defects.

Our laboratory originally synthesized strontium(Sr)-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite (Sr-α-CSH/n-HA) and demonstrated its ability to repair critical bone defects. This study attempted to incorporate aspirin into it to produce a better bone graft material for critical bone defects. After 5% Sr-α-CSH was prepared by coprecipitation and hydrothermal methods, it was mixed with aspirin solution of different concentrations (50 µg/ml, 200 µg/ml, 800 µg/ml and 3200 µg/ml) at a fixed liquid-solid ratio (0.54 v/w) to obtain aspirin-loaded Sr-α-CSH/n-HA composite. In vitro experiments were performed on the composite extracts. The tibial defects (3 mm*5 mm) in SD rat model were filled with the composite for 4 weeks and 12 weeks to evaluate its osteogenic capacity in vivo. Our results showed its capability of proliferation, migration and osteogenesis of BMSCs in vitro got improved. In vivo treatment with 800 µg/ml aspirin-loaded Sr-α-CSH/n-HA composite led to significantly more new bone formation in the defects compared with Sr-α-CSH/n-HA composite and significantly promoted the expression of osteogenic-related genes and inhibited osteoclast activity. In general, our research suggests that aspirin-loaded Sr-α-CSH/n-HA composite may have a greater capacity of repairing tibial defects in SD rats than simple Sr-α-CSH/n-HA composite.

Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance.

Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well-defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future.

Nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs with enhanced drug uptake and the activity of overcoming drug resistance.

Here, a nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs [biodegradable polymer-di-cisPt(IV)] for overcoming cisplatin drug resistance is reported. From the MTT assays, lower IC50 values of polymer-di-cisPt(IV) on A2780DDP cells than A2780 were observed with the lowest resistance factor of 0.7. Inductively coupled plasma mass spectroscopy results showed that more drugs were delivered into cancer cells and greater number of Pt-DNA adducts were formed with the use of the polymer-di-cisPt(IV) conjugate nanoparticles. By a mechanistic study with endocytosis inhibitors to treat A2780 cells, we proved that polymer-di-cisPt(IV) conjugate nanoparticles were internalized by the cancer cells through endocytosis rather than through passive diffusion or copper transporter 1-mediated active transportation. This well illustrates the way how the polymer-di-cisPt(IV) micelles overcome cisplatin resistance.