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The development of PtIV prodrugs which are selectively reduced within cancerous cells into their PtII therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep‐seated or large tumors is limited. To overcome this limitation, herein, the example of PtIV‐functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self‐assemble into nanoparticles was functionalized with PtIV complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer‐targeting peptides. Upon irradiation, the PtIV center is reduced to PtII and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple‐negative breast cancer tumor inside a mouse model. [ABSTRACT FROM AUTHOR]

Die Entwicklung von PtIV‐Prodrugs, die in Krebszellen selektiv in ihre therapeutisch wirksamen PtII‐Spezies reduziert werden, hat in den letzten Jahrzehnten zunehmend an Bedeutung gewonnen. Trotz jüngster Fortschritte in der Forschung werden die meisten untersuchten Verbindungen mit ultraviolettem oder blauem Licht angeregt. Da die Eindringtiefe des Lichts bei diesen Wellenlängen gering ist, ist die Behandlung von tiefsitzenden oder großen Tumoren begrenzt. Um diese Einschränkung zu überwinden, wird hier über ein Beispiel von PtIV‐funktionalisierten Nanopartikeln berichtet, die im NIR‐Bereich bei 808 nm angeregt werden können. Das Polymer‐Grundgerüst, das sich selbst zu Nanopartikeln zusammensetzen kann, wurde mit PtIV‐Komplexen für die Chemotherapie, Photosensibilisatoren für die photodynamische Immuntherapie und Kern‐/Krebs suchenden Peptiden funktionalisiert. Bei der Aussetzung zu Licht wird das PtIV‐Zentrum zu PtII reduziert und die axial koordinierten Liganden freigesetzt, was eine multimodale Behandlung ermöglicht. Die Nanopartikel reichern sich selektiv im Tumorgewebe an und haben in einem Mausmodell einen dreifach‐negativen Brustkrebstumor vernichtet. [ABSTRACT FROM AUTHOR]

Chemotherapy remains the primary treatment method for osteosarcoma after surgery. However, the lack of selectivity of chemotherapy for osteosarcoma leads to unpredictable therapeutic effects, undesirable side effects, and drug resistance. A platinum(IV) (Pt IV ) prodrug amphiphile (ALN-Pt IV -Lipo) covalently bound to alendronate (ALN) and a lipid tail is designed to overcome these limitations. ALN-Pt IV -Lipo can self-assemble into Pt IV lipid nanoparticles (APt IV ) for osteosarcoma targeting chemotherapy and bone destruction inhibition. It is demonstrated that APt IV achieved an eightfold increase in the eradication of osteosarcoma cells compared to cisplatin and threefold selective inhibition of osteosarcoma cells over breast cancer cells via APt IV in vitro. After intravenous injection, APt IV effectively accumulates at the osteosarcoma site in vivo, resulting in significantly suppressed primary osteosarcoma growth, and alleviation of bone destruction. Therefore, APt IV delivers a promising solution for enhanced chemotherapy targeting and bone destruction inhibition in osteosarcoma., (© 2023 Wiley-VCH GmbH.)

Patients treated with Pt-based anticancer drugs (Pt II ) often experience severe side effects and are susceptible to cancer recurrence due to the limited bioavailability of Pt II and tumor-induced immunosuppression. The exposure of phosphatidylserine on the cell's outer surface induced by Pt II results in profound immunosuppression through the binding of phosphatidylserine to its receptors on immune cells. Here, we report a novel approach for enhanced cancer chemoimmunotherapy, where a novel nuclear-targeting lipid Pt IV prodrug amphiphile was used to deliver a small interfering RNA (siXkr8) to simultaneously amplify Pt-DNA adducts and reduce the level of exposure of phosphatidylserine. This drug delivery vehicle is engineered by integrating the Pt IV prodrug with self-assembly performance and siXkr8 into a lipid nanoparticle, which shows tumor accumulation, cancer cell nucleus targeting, and activatable in a reduced microenvironment. It is demonstrated that nuclear-targeting lipid Pt IV prodrug increases the DNA cross-linking, resulting in increased Pt-DNA adduct formation. The synergistic effects of the Pt IV prodrug and siXkr8 contribute to the improvement of the tumor immune microenvironment. Consequently, the increased Pt-DNA adducts and immunogenicity effectively inhibit primary tumor growth and prevent tumor recurrence. These results underscore the potential of utilizing the nuclear-targeting lipid Pt IV prodrug amphiphile to enhance Pt-DNA adduct formation and employing siXkr8 to alleviate immunosuppression during chemotherapy.

Photodynamic therapy has been used as a treatment option for cancer; however, the existing TiO 2 photosensitizer does not have the ability to specifically target cancer cells. This lack of selectivity reduces its effectiveness in overcoming cancer resistance. To improve photodynamic therapy outcomes, an innovative solution is proposed. In this study, we report on the compounding of a zwitterionic covalent organic polymer (COP) with a TiO 2 photosensitizer for the first time. The aim is to overcome cancer cellular resistance. A one-pot synthetic strategy, which includes the construction of a porphyrin-based COP has been employed. This strategy has also been applied to the rapid preparation of anatase defective TiO 2 (TiO 2- x ). To improve the hydrophilic and antifouling properties of the polymer, zwitterion L-cysteine has been conjugated with a porphyrin-based COP using a thiol-ene "click chemistry" reaction. The novel zwitterionic porphyrin-based COP has the ability to trigger biodegradation under the acid microenvironment due to the presence of acid-sensitive β-thioether esters. When combined with TiO 2- x , the resultant nanocomposite produces an enhanced photodynamic therapy effect for drug-resistant cancer cells under NIR laser irradiation. This is due to the strong mutual sensitization of zwitterionic porphyrin-based COP and TiO 2- x . Importantly, the nanocomposite delivery system exhibits excellent cytocompatibility in the dark and has the potential to improve the accuracy of cancer diagnosis through fluorescence imaging. The results of this study demonstrate the potential application of this alternative nanocomposite delivery system for remote-controllable photodynamic therapy of tumors.

The development of Pt IV prodrugs which are selectively reduced within cancerous cells into their Pt II therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep-seated or large tumors is limited. To overcome this limitation, herein, the example of Pt IV -functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self-assemble into nanoparticles was functionalized with Pt IV complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer-targeting peptides. Upon irradiation, the Pt IV center is reduced to Pt II and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple-negative breast cancer tumor inside a mouse model., (© 2022 Wiley-VCH GmbH.)