Recent Advances of Platinum‐Based Anticancer Complexes in Combinational Multimodal Therapy

Abstract

Platinum drugs with manifest therapeutic effects are widely used, but their systemic toxicity and the drug resistance acquired by cancer cells limit their clinical applications. Thus, the exploration on appropriate methods and strategies to overcome the limitations of traditional platinum drugs becomes extremely necessary. Combination therapy of platinum drugs can inhibit tumor growth and metastasis in an additive or synergistic manner, and can potentially reduce the systemic toxicity of platinum drugs and overcome platinum‐resistance. This review summarizes the various modalities and current progress in platinum‐based combination therapy. The synthetic strategies and therapeutic effects of some platinum‐based anticancer complexes in the combination of platinum drugs with gene editing, ROS‐based therapy, thermal therapy, immunotherapy, biological modelling, photoactivation, supramolecular self‐assembly and imaging modality are briefly described. Their potential challenges and prospects are also discussed. It is hoped that this review will inspire researchers to have more ideas for the future development of highly effective platinum‐based anti‐cancer complexes.

Cu(ii) flavonoids as potential photochemotherapeutic agents

“…The biphasic mixture was then centrifuged for 5 minutes at ∼3000 rpm to separate the two layers. The concentrations of 1-6 in aqueous [1][2][3][4][5][6] aq and n-octanol [1][2][3][4][5][6] oct layers were determined using a UV-visible spectrophotometer by recording the absorbance of the complexes in the aqueous layer before and after vortex mixing. The partition coefficients were calculated using the equation log P = log{ [1][2][3][4][5][6] oct / [1][2][3][4][5][6] aq }.…”

“…[1][2][3] Nevertheless, their substantial inherent toxicity and tumor resistance impose restrictions on their clinical application, leading to their utilization only in combination therapy alongside other organic anticancer drugs. 4 Recently, other transition metal complexes have gained researchers' attention as next-generation photochemothera-peutics due to their spatiotemporal control, flexible structure, efficient redox chemistry, photo-physical properties and unique mechanism of action. [5][6][7][8] Differing from platinum drugs which establish covalent DNA cross-links, diverse categories of transition metal complexes, encompassing ruthenium, rhodium, iridium, osmium and others, have showcased their promise as potent contenders in the battle against cancer.…”

Antitumor Effect of Platinum-Modified STING Agonist MSA-2

“…Cisplatin is the leading anticancer drug, which is developed into classical Pt­(II) drugs (carboplatin, oxaliplatin, lobaplatin, nedaplatin, etc. ), and nonclassical Pt­(II) drugs (picoplatin, BBR3464, 56MESS) and Pt­(IV) prodrugs (satraplatin and Pt­(IV)-azide complexes) . Various modalities and recent advances in combination with platinum-based antitumor therapy were developed, for instances, platinum drugs combined with surgery, chemotherapy, radiation therapy, thermal therapy, gene editing, ROS-based therapy, and immunotherapy. , The platinum-based drug not only caused tumor cell death and remodeled the immunosuppressive microenvironment but also activated the cGAS-STING pathway in immune cells to enhance the antitumor immune response. , Therefore, we first synthesized a platinum-modified STING agonist MSA-2 (MSA-2-Pt) and supposed that it could induce cell death by Pt and activate the STING pathway by MSA-2.…”

Series of Desloratadine Platinum(IV) Hybrids Displaying Potent Antimetastatic Competence by Inhibiting Epithelial–Mesenchymal Transition and Arousing Immune Response

“…Platinum(II) drugs as the cornerstone of chemotherapies display fascinating antitumor performance in clinics by inducing serious DNA lesions. 22,23 Nevertheless, their effectiveness against metastatic cancers was rather plagued by severe side effects, drug resistance, and the immune suppressive TME. 24−26 The exploration of multifunctional platinum(IV) hybrids by incorporating diverse functional ligands supplies a promising strategy to discover novel antimetastatic platinum drugs.…”

“…Platinum­(II) drugs as the cornerstone of chemotherapies display fascinating antitumor performance in clinics by inducing serious DNA lesions. , Nevertheless, their effectiveness against metastatic cancers was rather plagued by severe side effects, drug resistance, and the immune suppressive TME. − The exploration of multifunctional platinum­(IV) hybrids by incorporating diverse functional ligands supplies a promising strategy to discover novel antimetastatic platinum drugs. − Inspired by these observations, DLT was incorporated into the platinum­(IV) system for the first time in this work with the aim of exploring novel platinum drugs with potent antiproliferative and antimetastatic properties.…”