Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

Xiangyu Zhang; Qingbin Liu; Tingting Zhang; Pei Gao; Hui Wang; Lu Yao; Jingwen Huang; Shulong Jiang

doi:10.1080/10717544.2022.2050845

Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

Drug Deliv. 2022 Dec;29(1):889-905. doi: 10.1080/10717544.2022.2050845.

Authors

Xiangyu Zhang^{1

2}, Qingbin Liu³, Tingting Zhang⁴, Pei Gao⁴, Hui Wang⁴, Lu Yao⁴, Jingwen Huang⁵, Shulong Jiang³

Affiliations

¹ Postdoctoral of Shandong University of Traditional Chinese Medicine, Jinan, China.
² Department of Pathology, Jining No. 1 People's Hospital, Jining Medical University, Jining, China.
³ Clinical Medical Laboratory Center, Jining No. 1 People's Hospital, Jining Medical University, Jining, China.
⁴ Jining No. 1 People's Hospital, Jining Medical University, Jining, China.
⁵ The First Affiliated Hospital of Bengbu Medical College, Tumor Hospital Affiliated to Bengbu Medical College, Bengbu, China.

Abstract

As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good in vitro cellular uptake, the NPs-ALN also inhibited tumor growth both in vitro and in vivo by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.

Keywords: Prostate cancer; bone metastasis; bone microenvironment; calcium phosphate nanoparticle; sonic hedgehog (SHH) protein.

MeSH terms

Bone Neoplasms* / drug therapy
Bone Neoplasms* / secondary
Docetaxel / pharmacology
Humans
Male
Prostate / metabolism
Prostatic Neoplasms* / pathology
Tumor Microenvironment

Substances

Docetaxel

Grants and funding

This research was supported through grants from the National Natural Science Foundation of China (Grant Nos. 81803097, 81873249, and 82074360), the Natural Science Foundation of Shandong Province (No. ZR2017QH005), the Young Taishan Scholars Program of Shandong Province (Grant No. tsqn201909200), and University Natural Science Research Project of Anhui Province (No. KJ2019A0313).