<p>Dual targeting curcumin loaded alendronate-hyaluronan- octadecanoic acid micelles for improving osteosarcoma therapy</p>

Abstract

Introduction Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity. Methods The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied. Results The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR. Conclusion The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.

GO-Y078, a Curcumin Analog, Induces Both Apoptotic Pathways in Human Osteosarcoma Cells via Activation of JNK and p38 Signaling

“…Curcumin is a well-known potential anti-cancer drug but with poor bioavailability due to its low aqueous solubility and the body’s rapid metabolism and systemic elimination. In the past decade, multifunctional micelles, liposomal nanoparticles, and liposomes followed by 3D printed scaffolds in a controlled delivery of curcumin to osteosarcoma cells were developed to accumulate targeting capacity for improving the therapeutic effect [ 31 , 32 , 33 ]. Moreover, several curcumin analogs have been also developed to improve poor bioavailability for chemotherapy in various cancers [ 27 ].…”

<p>^99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation</p>

“…HA can target to CD44-overexpressed solid cancer and cancer stem cells, such as breast, lung, and prostate cancers. [23][24][25][26][27][28] By modifying hydrophobic segments, HA-derivatives could self-assemble into nanoparticles that could be used for chemotherapeutics delivery. 29,30 For instance, Jeannot et al reported HA-b-poly(γ-benzyl-L-glutamate) nanoparticles that could actively target to the CD44 receptor for delivery of vorinostat and gefitinib with strong tumor growth inhibition.…”

Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Human Osteosarcoma

“…Nanomicelles adhered to the bone because of the composition and released curcumin in a sustained manner. The cytotoxic effect of the nanostructures was pronounced [ 156 ]. Polymeric micelles are now being explored for photodynamic therapy by using potential photosensitizers for OSA.…”