First, proteins such as serum albumin in blood deactivate cisplatin. [5] Second, cisplatin cannot be efficiently taken up by cisplatin-resistant cancer cells. [6] Third, intracellular biomolecules such as metallothionein (MT) and glutathione (GSH) may strongly bind and sequester cisplatin. [7] Fourth, the DNA of cancer cells that are damaged by cisplatin, can be repaired by proteins. [8] All these deactivation pathways hinder the curative effects of cisplatin. Some strategies have been developed to overcome the abovementioned deactivation pathways. For example, Pt(IV) prodrugs, which release cisplatin in cancer cells, have been developed. [9-12] Pt(IV) prodrugs are more resistant to ligand substitution reactions than cisplatin because Pt(IV) centers are saturated and kinetically more inert. [1] Thus, Pt(IV) can minimize unwanted side reactions with biomolecules prior to DNA binding. Another strategy to overcome deactivation is to combine cisplatin with other anticancer agents such as paclitaxel, 5-fluorouracil, gemcitabine or ruthenium complexes. [13-16] Mixtures of anticancer agents possess multiple targets and actions; this strategy strengthens the therapeutic effects via the different anticancer mechanisms of the different agents. [14] A third strategy to overcome deactivation is to use nanocarriers for the delivery of cisplatin. [17,18] Some Drug resistance is a major problem in cancer treatment. Herein, the design of a dual-responsive Pt(IV)/Ru(II) bimetallic polymer (PolyPt/Ru) to treat cisplatin-resistant tumors in a patient-derived xenograft (PDX) model is reported. PolyPt/Ru is an amphiphilic ABA-type triblock copolymer. The hydrophilic A blocks consist of biocompatible poly(ethylene glycol) (PEG). The hydrophobic B block contains reduction-responsive Pt(IV) and red-light-responsive Ru(II) moieties. PolyPt/Ru self-assembles into nanoparticles that are efficiently taken up by cisplatin-resistant cancer cells. Irradiation of cancer cells containing PolyPt/Ru nanoparticles with red light generates 1 O 2 , induces polymer degradation, and triggers the release of the Ru(II) anticancer agent. Meanwhile, the anticancer drug, cisplatin, is released in the intracellular environment via reduction of the Pt(IV) moieties. The released Ru(II) anticancer agent, cisplatin, and the generated 1 O 2 have different anticancer mechanisms; their synergistic effects inhibit the growth of drugresistant cancer cells. Furthermore, PolyPt/Ru nanoparticles inhibit tumor growth in a PDX mouse model because they circulate in the bloodstream, accumulate at tumor sites, exhibit good biocompatibility, and do not cause side effects. The results demonstrate that the development of stimuli-responsive multi-metallic polymers provides a new strategy to overcome drug resistance.
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the "therapeutic window" would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru-containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru-containing block, which contains red-light-cleavable (650-680 nm) drug-Ru complex conjugates. The block copolymer self-assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug-Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru-containing polymer for photoactivated chemotherapy in a tumor-bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red-light-responsive Ru-containing polymer provides a new platform for phototherapy against hypoxic tumors.
A new class of organic cathode interfacial layer (CIL) materials based on isoindigo derivatives (IID) substituted with pyridinium or sulfonate zwitterion groups were designed, synthesized, and applied in polymer solar cells (PSCs) with PTB7:PCBM (PTB7: polythieno[3,4-b]-thiophene-co-benzodithiophene and PCBM: [6,6]-phenyl C71-butyric acidmethyl ester) as an active layer. Compared with the control device, PSCs with an IID-based CIL show simultaneous enhancement of open-circuit voltage (V), short-circuit current (J), and fill factor (FF). Systematic optimizations of the central conjugated core and side flexible alcohol-soluble groups demonstrated that isoindigo-based CIL material with thiophene and sulfonate zwitterion substituent groups can efficiently enhance the PSC performance. The highest power conversion efficiency (PCE) of 9.12%, which is 1.75 times that of the control device without CIL, was achieved for the PSC having an isoindigo-based CIL. For the PSCs with an isoindigo-based CIL, the molecule-dependent performance property studies revealed that the central conjugated core with D-A-D characteristics and the side chains with sulfonate zwitterions groups represents an efficient strategy for constructing high performance CILs. Our study results may open a new avenue toward high performance PSCs.
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