Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

Abstract

To develop the next-generation Pt drug with remarkable activity and low toxicity to maximally inhibit tumor growth, we optimized a Pt(II) thiosemicarbazone compound (C4) with remarkable cytotoxicity to SK-N-MC cells and then constructed a new human serum albumin−C4 (HSA− C4) complex delivery system. The in vivo results showed that C4 and the HSA−C4 complex have remarkable therapeutic efficiency and almost no toxicity; they induced apoptosis and inhibited tumor angiogenesis. This system showed potential as a practical Pt drug. This study could pave the way for developing next-generation dual-targeted Pt drugs and achieving their targeting therapy for cancer.

Developing a Hetero-Trinuclear Erbium(III)–Copper(II) Complex Based on Apoferritin: Targeted Photoacoustic Imaging and Multimodality Therapy of Tumor

“…Apoptosis is one of the key mechanisms resulting from chemotherapeutic drugs. ,, Thus, we investigated whether apoptosis was induced by ErCu 2 and ErCu 2 @AFt NPs. Annexin V-FITC/PI staining was used to detect the apoptosis of MDA-MB-231 cells.…”

“…At the same time, we should overcome the shortcomings of metal complexes, such as lack of targeting ability and significant off-target toxicity, which brought out serious systemic toxicity in vivo . At present, protein-based drug delivery systems have been one of the most promising strategies to overcome these shortcomings. − Indeed, apoferritin (AFt) is an ideal candidate due to its nanoscale structure, biocompatibility, biodegradability, and nontoxicity. − …”

Developing a Multitargeted Anticancer Palladium(II) Agent Based on the His-242 Residue in the IIA Subdomain of Human Serum Albumin

“…On the one hand, there is a large flexible hydrophobic cavity in the IIA subdomain of HSA that can allow drugs with different molecular structures to bind; ,− On the other hand, the His-242 residue in the HSA IIA subdomain can replace a leaving group of the metal compound and coordinate with the metal center to form the HSA-metal compound complex. ,− Taking into consideration these factors, to obtain the next-generation metal drugs to overcome the deficiencies of Pt drugs and optimize their antitumor behavior in vivo , we encompassed inorganic medicinal chemistry, structural biology, and pharmaceutics to develop a Pd­(II) thiosemicarbazone agent with multiple actions on different components in the TME based on the His-242 residue of the HSA IIA subdomain (Figure ). First, we designed and synthesized a series of Pd­(II) 2-benzoylpyridine thiosemicarbazone compounds (Figure ), and then obtained a Pd agent (5b) with remarkable cytotoxicity by studying their structure–activity relationships to cancer cells in vitro .…”

Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis

“…Pyroptosis is a type of immunogenic cell death (ICD) that can be induced by caspase-3 and elicits an antitumor immune response, which provides a good opportunity to effectively inhibit primary and metastatic tumor cells in the treatment of solid tumors. − Interestingly, chemotherapy drugs may trigger the gasdermin E (GSDME)-mediated pyroptosis process and an immunological response. , In fact, it has become a promising strategy for inhibiting tumor growth and metastasis by designing novel anticancer drugs based on GSDME-mediated pyroptosis. , In the past several decades, on one hand, ruthenium (Ru) complexes have been extensively studied as a potential class of next-generation metal drugs owing to their low systemic toxicity, limited side effects, high antitumor activity, and more diverse biological activities compared to those of Pt drugs in vitro and in vivo ; − on the other hand, metal thiosemicarbazone complexes have also become promising next-generation metal drugs because of their remarkable inhibitory effect on tumor growth. − Thus, to integrate the inhibition of tumor growth and metastasis, we proposed to design a new Ru­(III) thiosemicarbazone complex to trigger GSDME-mediated pyroptosis and an immunological response.…”