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Cisplatin is one of the most widely used chemotherapeutic agents for various solid tumors in the clinic due to its high efficacy and broad spectrum. The antineoplastic activity of cisplatin is mainly due to its ability to cross-link with DNA, thus blocking transcription and replication. Unfortunately, the clinical use of cisplatin is limited by its severe, dose-dependent toxic side effects. There are approximately 40 specific toxicities of cisplatin, among which nephrotoxicity is the most common one. Other common side effects include ototoxicity, neurotoxicity, gastrointestinal toxicity, hematological toxicity, cardiotoxicity, and hepatotoxicity. These side effects together reduce the life quality of patients and require lowering the dosage of the drug, even stopping administration, thus weakening the treatment effect. Few effective measures exist clinically against these side effects because the exact mechanisms of various side effects from cisplatin remain still unclear. Therefore, substantial effort has been made to explore the complicated biochemical processes involved in the toxicology of cisplatin, aiming to identify effective ways to reduce or eradicate its toxicity. This review summarizes and reviews the updated advances in the toxicological research of cisplatin. We anticipate to provide insights into the understanding of the mechanisms underlying the side effects of cisplatin and designing comprehensive therapeutic strategies involving cisplatin. OVERVIEW OF CISPLATIN1.1. Chemistry of Cisplatin. Cisplatin, chemically named cis-diamminedichloroplatinum (CDDP), was synthesized by M. Peyrone in 1844 for the first time. However, this compound did not gain much scientific attention until 1965. In this year, Rosenberg found that the electrolytic product of platinum electrodes can inhibit the growth of Escherichia coli and was later characterized to be CDDP. 1 After more than 10 years of bench and preclinic research as well as clinical trials, CDDP was approved by the FDA in 1978 for clinical use as a chemotherapeutic agent with the name cisplatin. Since then, cisplatin has been used to treat various human malignancies, including ovarian cancer, cervical cancer, testicular cancer, head and neck cancer, nonsmall cell lung cancer, and many other solid tumors. 2−4 Cisplatin is centered on a platinum atom which coordinates with two chlorine atoms and two ammonia groups to form a planar quadrilateral compound. The two chlorine atoms are on the same side (Figure 1). Initially, it was widely accepted that cisplatin enters cells by passive transport. However, studies in recent years have shown that the copper transport protein CTR1 and organic cation transporters (OCTs) also play important roles in the transport of cisplatin. 5,6 Outside cells, cisplatin is not susceptible to hydrolysis due to the high concentration of chloride ions (approximately 100 mM) in blood. Once in cells, cisplatin undergoes slow hydrolysis to form the cationic monoaqua and/or diaqua complexes (Figure 1) due to a

Defect passivation is an effective method to improve the performance of perovskite solar cells. In this study, four phenethylammonium iodides featuring different functional groups directly linking to the benzene ring are introduced on the surface of perovskite films ((FAPbI3)1–x (MAPbBr3–y Cl y ) x ) to investigate their passivation effects. It is found that the electron density of the benzene ring has significant influence on the interfacial passivation: phenethylammonium iodide with electron-donating groups (methoxyl and methyl) present favorable passivation effects, while the salt with electron-withdrawing group (nitro) delivers undesirable impacts. The passivation is attributed to the electrostatic interaction between the benzene ring and the undercoordinated Pb2+ ions. The salt-treated films are employed to fabricate solar cells, and an efficiency of 22.98% is achieved. In addition, the treated device shows good long-term stability for 1000 h of storage in a dark, ambient environment.

Although outstanding power conversion efficiency (PCE) has been achieved in flexible perovskite solar cells, unsatisfactory operational stability and toxicity caused by the moisture transmittance of polymer packaging are still the bottleneck challenges that limit their applications. Herein, inspired by the non-selective permeability of inactivated cell membrane, the diphosphatidyl-glycerol (Di-g) is tactfully introduced as a self-shield interface upon the perovskite layer. 96% of lead leakage is suppressed because the amphipathic Di-g can simultaneously bind tightly to the divalent lead ion and afford an interfacial water-resistance. More importantly, the gradient distribution of lattice residual stress perpendicular to the substrate are optimized. The resultant flexible devices achieve a PCE of 20.29% and 15.01% at effective areas of 1.01 and 21.82 cm 2 respectively, yielding excellent environmental and mechanical stability. This strategy exhibits the feasibility of developing interfacial encapsulation to stabilize scalable PSCs with negligible lead leakage.