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Theranostics 2022Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used for chemotherapeutic eradication of cancer. However, the side effects of platinum drugs,... (Review)
Review
Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used for chemotherapeutic eradication of cancer. However, the side effects of platinum drugs, such as lack of selectivity, high systemic toxicity, and drug resistance, seriously limit their clinical application. With advancements in nanotechnology and chemical synthesis, Pt-based anti-cancer drugs have made great progress in cancer therapy in recent years. Many strategies relied on the anti-cancer mechanism similar to cisplatin and achieved some success by modifying existing platinum drugs. Pt-based nanodrugs, such as platinum nanoclusters, have novel anti-cancer mechanisms and great potential in tumor-targeted therapy and have shown promising results in clinical application. In this review, we systematically explored the development of first-line platinum chemotherapy drugs in the clinic and their anti-cancer mechanisms. We also summarize the progress of Pt-based anti-cancer drug application in cancer therapy, emphasizing their modification to enhance the anti-tumor effect. Finally, we address challenges faced by platinum chemotherapy drugs, especially Pt nanocluster-based nanodrugs, in cancer treatment. The new platinum drugs and their targeted modifications undoubtedly provide a promising prospect for improving the current anti-cancer treatments.
Topics: Antineoplastic Agents; Carboplatin; Cisplatin; Humans; Neoplasms; Oxaliplatin; Platinum
PubMed: 35265202
DOI: 10.7150/thno.69424 -
Angewandte Chemie (International Ed. in... Jan 2023Triggering receptor expressed on myeloid cells-2 (TREM2) is a key pro-tumorigenic marker of tumor-infiltrating macrophages, showing potent immunosuppressive activity in...
Triggering receptor expressed on myeloid cells-2 (TREM2) is a key pro-tumorigenic marker of tumor-infiltrating macrophages, showing potent immunosuppressive activity in tumor microenvironment. A platinum(IV) complex OPA derived from oxaliplatin (OP) and artesunate (ART) exhibited direct cytotoxicity against human colon cancer cells and immunomodulatory activity to inhibit TREM2 on macrophages in vitro and vivo. Furthermore, OPA deterred the tumor growth in mouse models bearing MC38 colorectal tumor by reducing the number of CD206 and CX CR1 immunosuppressive macrophages; it also promoted the expansion and infiltration of immunostimulatory dendritic, cytotoxic T, and natural killer cells. OPA is the first small-molecular TREM2 inhibitor capable of relieving immunosuppressive tumor microenvironment and enhancing chemical anticancer efficiency of a platinum drug, thus showing typical characteristics of a chemoimmunotherapeutic agent.
Topics: Animals; Mice; Humans; Platinum; Antineoplastic Agents; Myeloid Cells; Macrophages; Immunosuppressive Agents; Colonic Neoplasms; Tumor Microenvironment; Membrane Glycoproteins; Receptors, Immunologic
PubMed: 36259513
DOI: 10.1002/anie.202213337 -
Journal of Controlled Release :... Dec 2022Platinum (Pt)-based chemotherapy has been necessary for clinical cancer treatment. However, traditional bivalent drugs are hindered by poor physicochemical properties,... (Review)
Review
Platinum (Pt)-based chemotherapy has been necessary for clinical cancer treatment. However, traditional bivalent drugs are hindered by poor physicochemical properties, severe toxic side effects, and drug resistance. Currently, elemental Pt(0) nanotherapeutics (NTs) have emerged to tackle the dilemma. The inherent acid-responsiveness of Pt(0) NTs could help to improve tumor selectivity and alleviate toxic effects. Moreover, the metal nature of Pt facilitates the great combination of Pt(0) NTs with photothermal and photodynamic therapy and imaging-guided diagnosis. Based on recent important researches, this review provides an updated introduction to Pt(0) NTs. First, the challenges of traditional Pt-based chemotherapy have been outlined. Then, Pt(0) NTs with multiple applications of tumor theranostics have been overviewed. Furthermore, the combinations of Pt(0) NTs with other therapeutical modalities are introduced. Last but not least, we envision the possible challenges and prospects associated with Pt(0) NTs.
Topics: Platinum; Cell Line, Tumor; Photochemotherapy; Neoplasms
PubMed: 36273531
DOI: 10.1016/j.jconrel.2022.10.021 -
Biomolecules Dec 2019Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these... (Review)
Review
Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells' fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints' expression.
Topics: Animals; Antineoplastic Agents; Humans; Immune System; Immunologic Factors; Neoplasms; Platinum
PubMed: 31861811
DOI: 10.3390/biom10010013 -
Medycyna Pracy Jul 2019Platinum nanoparticles (PtNPs) have been widely used not only in industry, but above all in medicine and diagnostics. However, there are disturbing reports related to... (Review)
Review
Platinum nanoparticles (PtNPs) have been widely used not only in industry, but above all in medicine and diagnostics. However, there are disturbing reports related to the toxic effects of nanoplatinum, which is the main reason why the authors of this study have decided to review and analyze literature data related to its toxicity and impact on human health. While PtNPs may be absorbed by the respiratory and digestive tract, and can penetrate through the epidermis, there is no evidence concerning their absorption through the skin. Platinum nanoparticles accumulate mainly in the liver and spleen although they also reach other internal organs, such as lungs, kidneys or heart. Toxicokinetics of platinum nanoparticles depends strongly on the particle size. Only few studies regarding platinum nanoparticles toxicity have been conducted. Animals intratracheally exposed to platinum nanoparticles have demonstrated an increased level of proinflammatory cytokines in bronchoalveolar lavage which confirms inflammatory response in the lungs. Oral administration of PtNPs can cause inflammatory response and induce oxidative stress. Nanoplatinum has been found to induce hepatotoxicity and nephrotoxicity via the intravenous route. It can cause DNA damage and cellular apoptosis without significant cytotoxicity. There are no research studies on its carcinogenicity. Fetal or maternal toxicity has not been observed, but an increased mortality and a decreased growth of the offspring have been demonstrated. Platinum nanoparticles may permeate the skin barrier but there is no evidence for their absorption. Due to the insufficient number of tests that have been carried out to date, it is not possible to clearly determine the occupational exposure limit value; however, caution is recommended to employees exposed to their effects. Med Pr. 2019;70(4):487-95.
Topics: Animals; Humans; Inflammation; Metal Nanoparticles; Occupational Exposure; Oxidative Stress; Particle Size; Platinum
PubMed: 31162484
DOI: 10.13075/mp.5893.00847 -
International Journal of Clinical... Mar 2023Platinum drugs, as a class of widely used chemotherapy agents, frequently appear in the treatment of cancer at different phrases. However, platinum resistance is the... (Review)
Review
Platinum drugs, as a class of widely used chemotherapy agents, frequently appear in the treatment of cancer at different phrases. However, platinum resistance is the major bottleneck of platinum drugs for exerting anti-tumor effect. At present, the mechanism of platinum resistance has been thoroughly explored in terms of drug delivery methods, DNA damage repair function, etc., but it has not yet been translated into an effective weapon for reversing platinum resistance. Recently, autophagy has been proved to be closely related to platinum resistance, and the involved molecular mechanism may provide a new perspective on platinum resistance. The aim of this review is to sort out the studies related to autophagy and platinum resistance, and to focus on summarizing the relevant molecular mechanisms, so as to provide clues for future studies related to autophagy and platinum resistance.
Topics: Humans; Platinum; Drug Resistance, Neoplasm; Antineoplastic Agents; Neoplasms; Autophagy
PubMed: 36705869
DOI: 10.1007/s10147-023-02301-5 -
Wiley Interdisciplinary Reviews.... Mar 2017Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse... (Review)
Review
Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier-based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor-specific localization as well as tumor cell uptake. The introduction of stimuli-responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor-localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real-time monitoring the distribution of drug-loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum-based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Metal Nanoparticles; Mice; Neoplasms; Platinum; Theranostic Nanomedicine
PubMed: 27094725
DOI: 10.1002/wnan.1410 -
Metallomics : Integrated Biometal... Apr 2023Platinum(II) coordination compounds are widely applied in clinics as anticancer drugs. In this review, we provide a summary of the reports on cytotoxic properties of... (Review)
Review
Platinum(II) coordination compounds are widely applied in clinics as anticancer drugs. In this review, we provide a summary of the reports on cytotoxic properties of platinum(II) complexes of selenium donor ligands along with a brief description of their structural features. It has been observed that the platinum(II) complexes of selenones and selenoethers display reasonable antitumor properties and in some cases their cytotoxic activity is greater than cisplatin. The complexes containing NH3 ligands along with selenones were found to exhibit better cytotoxicity compared to the binary Pt-selenone complexes. The mechanistic insights showed that these complexes exert antitumor activity through reactive oxygen species (ROS) generation and induction of apoptosis. The platinum-selenoether coordination compounds can self-assemble into spherical aggregates capable of self-delivery. The self-assembled Pt-selenium aggregates induce cell apoptosis via ROS, which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays.
Topics: Platinum; Selenium; Ligands; Reactive Oxygen Species; Organoplatinum Compounds; Antineoplastic Agents
PubMed: 36918206
DOI: 10.1093/mtomcs/mfad020 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2024Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy.... (Review)
Review
Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy. Increasing evidences indicate that the antitumor activity of platinum complexes is not limited to chemical killing effects, but also extends to immunomodulatory actions. This review introduced the general concept of chemoimmunotherapy and summarized the progress of platinum complexes as chemoimmunotherapeutic agents in recent years. Platinum complexes could be developed into inducers of immunogenic cell death, blockers of immune checkpoint, regulators of immune signaling pathway, and modulators of tumor immune microenvironment, etc. The synergy between chemotherapeutic and immunomodulatory effects reinforces the antitumor activity of platinum complexes, and helps them circumvent the drug resistance and systemic toxicity. The exploration of platinum complexes for chemoimmunotherapy may create new opportunities to revive the discovery of metal anticancer drugs.
Topics: Humans; Platinum; Antineoplastic Agents; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 38171804
DOI: 10.1002/chem.202302948 -
Molecules (Basel, Switzerland) Feb 2017Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be... (Review)
Review
Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation reaction kinetics) that determine site-specific toxicity; second, the impact on RNA molecules. Knowledge of the 'RNA world' has dramatically changed our understanding of cellular and molecular biology. The inherent RNA-crosslinking properties should make platinum-based drugs interact with coding and non-coding RNAs. Third, we will discuss the impact on the immune system, which is now recognized to substantially contribute to chemotherapy efficacy. Together, platinum drugs are in fact old drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave the way to new drugs or an improved application of the already existing compounds.
Topics: Animals; Antineoplastic Agents; DNA Damage; Gene Expression Regulation; Humans; Hydrolysis; Immune System; Neoplasms; Platinum; Signal Transduction; Structure-Activity Relationship; Tissue Distribution
PubMed: 29760371
DOI: 10.3390/molecules22030382