Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption
The “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic str...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520306158 |
| _version_ | 1818380798640783360 |
|---|---|
| author | Yanjuan Huang Zhanghong Xiao Zilin Guan Zishan Zeng Yifeng Shen Xiaoyu Xu Chunshun Zhao |
| author_facet | Yanjuan Huang Zhanghong Xiao Zilin Guan Zishan Zeng Yifeng Shen Xiaoyu Xu Chunshun Zhao |
| author_sort | Yanjuan Huang |
| collection | DOAJ |
| description | The “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn2+ crosslinking for combination therapy was reported. The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo. Additionally, DZ@ALN could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro. Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo, eventually leading to the breakdown of “vicious cycle” without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis. |
| first_indexed | 2024-12-14T02:24:25Z |
| format | Article |
| id | doaj.art-31a80dbe3f834c2c93082bcad00fd8b7 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-14T02:24:25Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-31a80dbe3f834c2c93082bcad00fd8b72022-12-21T23:20:25ZengElsevierActa Pharmaceutica Sinica B2211-38352020-12-01101223842403Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorptionYanjuan Huang0Zhanghong Xiao1Zilin Guan2Zishan Zeng3Yifeng Shen4Xiaoyu Xu5Chunshun Zhao6School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaCorresponding author. Tel./fax: +86 20 39943118.; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaThe “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn2+ crosslinking for combination therapy was reported. The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo. Additionally, DZ@ALN could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro. Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo, eventually leading to the breakdown of “vicious cycle” without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis.http://www.sciencedirect.com/science/article/pii/S2211383520306158Bone metastasisBone targetingOsteolysisZoledronateCisplatin |
| spellingShingle | Yanjuan Huang Zhanghong Xiao Zilin Guan Zishan Zeng Yifeng Shen Xiaoyu Xu Chunshun Zhao Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption Acta Pharmaceutica Sinica B Bone metastasis Bone targeting Osteolysis Zoledronate Cisplatin |
| title | Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| title_full | Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| title_fullStr | Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| title_full_unstemmed | Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| title_short | Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| title_sort | bone seeking nanoplatform co delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption |
| topic | Bone metastasis Bone targeting Osteolysis Zoledronate Cisplatin |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520306158 |
| work_keys_str_mv | AT yanjuanhuang boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT zhanghongxiao boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT zilinguan boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT zishanzeng boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT yifengshen boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT xiaoyuxu boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption AT chunshunzhao boneseekingnanoplatformcodeliveringcisplatinandzoledronateforsynergistictherapyofbreastcancerbonemetastasisandboneresorption |