Ultrasmall platinum nanoclusters: A potent chemotherapeutic drug for cancer-specific DNA damage with optimizing therapeutic efficacy while minimizing systemic toxicity

被引：7

作者：

Zhang, Chunyu ^{[1
,2
]}

Zhang, Na ^{[5
]}

Niu, Wenchao ^{[3
]}

Li, Ruihan ^{[1
,2
]}

Liu, Yanna ^{[1
,2
]}

Mu, Yanling ^{[1
,2
]}

Xu, Chao ^{[4
]}

Yao, Qingqiang ^{[1
,2
]}

Gao, Xueyun ^{[3
]}

机构：

[1] Shandong First Med Univ & Shandong Acad Med Sci, Key Lab Biotechnol Drugs Natl Hlth Commiss, Natl Key Lab Adv Drug Delivery Syst,Shandong Acad, Sch Pharmaceut Sci,Key Lab Rare & Uncommon Dis Sh, Jinan 250117, Shandong, Peoples R China

[2] Shandong First Med Univ & Shandong Acad Med Sci, Key Lab Biotechnol Drugs Natl Hlth Commiss, Natl Key Lab Adv Drug Delivery Syst,Shandong Acad, Inst Mat Med,,Key Lab Rare & Uncommon Dis Shandon, Jinan 250117, Shandong, Peoples R China

[3] Beijing Univ Technol, Dept Chem, Beijing 100124, Peoples R China

[4] Shandong Agr Univ, Coll Chem & Mat Sci, Shandong 271018, Peoples R China

[5] Jinan Second Peoples Hosp, Dept Internal Med, Jinan 250000, Shandong, Peoples R China

来源：

NANO TODAY | 2024年 / 55卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Platinum nanocluster; Anticancer therapy; Systemic toxicity; Mechanism; DNA damage; IN-VIVO; CISPLATIN; DELIVERY; NANOPARTICLE; PRODRUGS; GROWTH; LHRH;

D O I：

10.1016/j.nantod.2024.102195

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Platinum chemotherapy drugs, represented by cisplatin, have been widely used in cancer therapy. While they are effective, their use is limited by their adverse effects in long-term administration, especially the lack of selectivity and high systemic toxicity. Encouragingly, molecular-like platinum nanoclusters, as a bridge between nanomedical and small molecular drugs, provide an attractive opportunity to completely change the current status of cancer treatment, mainly due to their unique structural advantages, making them highly efficient and low toxic. Functional modifications offer a promising avenue to enhance template-modified platinum nanoclusters' selectivity and safety, addressing systemic toxicity concerns. Concurrently, leveraging tumor heterogeneity facilitates drug bioactivity via metabolism, thereby augmenting therapeutic efficacy. Herein, we utilized iRGD-modified bovine serum albumin (BSA-iRGD) as the protective molecule to construct platinum nanoclusters drug (PtNC@BSA-iRGD) directly under mild conditions. The new type of chemotherapeutic drug PtNC@BSA-iRGD exhibits excellent antitumor activity in vitro/vivo, in comparison to clinical commercial first-line carboplatin. This powerful antitumor effect is attributed to its selective uptake by tumor cells through receptor-mediated endocytosis. The release of platinum ions inhibits DNA replication by forming DNA-Pt complexes, activates apoptosis pathways, and ultimately induces tumor cell apoptosis. More impressively, compared to first-line platinum chemotherapy drugs, PtNC@BSA-iRGD has superior biocompatibility while possessing higher tumor inhibitory activity in vivo during medication treatment. This feature compensates for the shortcomings of clinical chemotherapy platinum-based drugs. This study provides novel insights into exploring new forms of metal cluster-based platinum drugs with high efficiency for optimizing therapeutic efficacy while minimizing systemic toxicity.

引用

页数：12