Corrosion‐Activated Chemotherapeutic Function of Nanoparticulate Platinum as a Cisplatin Resistance‐Overcoming Prodrug with Limited Autophagy Induction

Abstract

Despite nanoparticulate platinum (nano-Pt) has been validated to be acting as a platinum-based prodrug for anticancer therapy, the key factor in controlling its cytotoxicity remains to be clarified. In this study, it is found that the corrosion susceptibility of nano-Pt can be triggered by inducing the oxidization of superficial Pt atoms, which can kill both cisplatin-sensitive/resistance cancer cells. Direct evidence in the oxidization of superficial Pt atoms is validated to observe the formation of platinum oxides by X-ray absorption spectroscopy. The cytotoxicity is originated from the dissolution of nano-Pt followed by the release of highly toxic Pt ions during the corrosion process. Additionally, the limiting autophagy induction by nano-Pt might prevent cancer cells from acquiring autophagy-related drug resistance. With such advantages, the possibility of further autophagy-related drug resistance could be substantially reduced or even eliminated in cancer cells treated with nano-Pt. Moreover, nano-Pt is demonstrated to kill cisplatin-resistant cancer cells not only by inducing apoptosis but also by inducing necrosis for pro-inflammatory/inflammatory responses. Thus, nano-Pt treatment might bring additional therapeutic benefits by regulating immunological responses in tumor microenvironment. These findings support the idea that utilizing nano-Pt for its cytotoxic effects might potentially benefit patients with cisplatin resistance in clinical chemotherapy.

Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy

“…Extant literature reports that cellular response to the cytotoxic agents (e.g., doxorubicin and cisplatin) includes life cycle inhibition or induction of death by apoptosis. Moreover, excessively high concentrations of such cytotoxic substances can induce cell death by necrosis [69][70][71]. The hybrid membrane-coated nanoparticle system-based specific internalization is expected to increase the intracellular concentration of drugs that might act synergistically to exhibit enhanced anticancer effects.…”

Near Infrared‐Activatable Platinum‐Decorated Gold Nanostars for Synergistic Photothermal/Ferroptotic Therapy in Combating Cancer Drug Resistance

“…Moreover, STEM images of the supernatants (Figure S4, Supporting Information) also suggested a disassembly of smaller nanoclusters (<5 nm) and/or metal ions from the Pt‐AuNS after efficient photothermal heating, which enabled the detection of a greater number of oxidized metallic species. [ 20 ] By contrast, NIR irradiation led to a variety of irregular and fragmented nanoparticles from the AuNS. The formation of larger sized Au nanoparticles may yield less activities in the subsequent reactions.…”

Microwave-Synthesized Platinum-Embedded Mesoporous Silica Nanoparticles as Dual-Modality Contrast Agents: Computed Tomography and Optical Imaging

“…Our preliminary results implicated that MSNs-Pt have much higher therapeutic efficacy than PEG-MSNs-Pt in both in vitro and in vivo experiments. Likewise, it was demonstrated that nano-Pt triggered the autophagy and immunological responses in the tumor area [41]. These preclinical experiments are currently ongoing; we are focusing on the underlying molecular mechanisms of therapeutic effects rendered by MSNs-Pt with the nPtNP distributions on the different topological domains of MSNs, i.e., nPtNPs reduced on the MSN surface and surface/channels, etc.…”

“…It is worth noting that PtNPs exhibit high catalytic activity, scavenging the singlet oxygen and superoxide to protect cells [36,37,38]. On the other hand, nanoparticulate Pt (nano-Pt) showed cisplatin-like function to inhibit cancer cell progression, cytotoxicity and less drug resistance [41]. Previous reports also used microwave-assisted methods to synthesize mesoporous silica aerogel-supported PtNPs (SAP) for a proton exchange membrane fuel cell [42].…”