Disrupting stromal barriers to enhance photothermal-chemo therapy using a halofuginone-loaded Janus mesoporous nanoplatform.

Abstract

Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 μg/mg). The antitumor experiments showed that the survival rate of 4 T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 μg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p < 0.0001) and HF (152 vs. 419 mm3, p = 0.0208). In addition, immunohistochemistry of tumor tissues indicated that JPMO-Pt-HF obviously reduced the relative collagen and α-smooth muscle actin (α-SMA) area fraction. Taken together, this research designs a new platform that not only possesses the ability to degrade the tumor matrix but also combines PTT and chemotherapeutic effects, and holds promise for effective tumor treatment.

• Authors: Rui Tang, Meng Dang, Xiaojun Zhang, Jun Tao, Wenhui Shi, Wei Lu, Ruifa Yu, Xiaodan Su, Yuxia Tang, Zhaogang Teng
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 610 Pg. 313-320 (Mar 15 2022) ISSN: 1095-7103 [Electronic] United States
• PMID: 34923269 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Piperidines
• Quinazolinones
• Doxorubicin
• halofuginone

Topics

• Animals
• Cell Line, Tumor
• Doxorubicin
• Drug Delivery Systems
• Humans
• Hyperthermia, Induced
• Mice
• Mice, Inbred BALB C
• Nanoparticles
• Phototherapy
• Photothermal Therapy
• Piperidines
• Quinazolinones