An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response

Wang, Na; Deng, Zhiqin; Zhu, Qi; Zhao, Jianxiong; Xie, Kai; Shi, Peng; Wang, Zhigang; Chen, Xianfeng; Wang, Feng; Shi, Jiahai; Zhu, Guangyu

doi:10.1039/d1sc02941j

Cited by 20 publications

(21 citation statements)

References 56 publications

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“…For example, small-molecule Pt(IV) prodrugs may not be stable enough in the circulation system and are also limited by an insufficient circulatory half-life, which reduces Pt accumulation in tumor tissues, and thus, restricts the drug efficacy [ 29 , 30 ]. Additionally, conventional Pt(IV) prodrugs do not have the property of controllable activation, leading to adverse effects in off-target tissues [ 129 , 130 , 131 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Recently the Pt(IV) prodrug trans, trans, trans-[Pt(pyridine)2(N3)2(OH)2] (Pt1) and its coumarin derivative trans, trans, trans-[Pt(pyridine)2(N3)2(OH)(coumarin-3-carboxylate)] (Pt2) were discovered as agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells [ 129 , 130 , 131 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

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Metallo-Drugs in Cancer Therapy: Past, Present and Future

et al. 2022

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Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. For these reasons, the identification of new drug designs and therapeutic strategies that could target cancer cells while leaving normal cells unaffected still continues to be a challenge. Despite advances that have led to the development of new therapies, treatment options are still limited for many types of cancers. This review provides an overview of platinum, copper and ruthenium metal based anticancer drugs in clinical trials and in vitro/in vivo studies. Presumably, copper and ruthenium complexes have greater potential than Pt(II) complexes, showing reduced toxicity, a new mechanism of action, a different spectrum of activity and the possibility of non-cross-resistance. We focus the discussion towards past, present and future aspects.

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Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Metallo-Drugs in Cancer Therapy: Past, Present and Future

et al. 2022

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“…In the subsequent study, Phorbiplatin 8 prodrug was loaded onto NaYbF4:Er@NaYF4:Yb/ Nd@NaYF4:Ca nanocrystals (NCs) via linkage with amine groups ( Figure 6 ) to increase the Pt(IV) prodrug 8 stability in blood and shift the activation wavelength further in the deeply-penetrating NIR region [ 61 ]. Using ESI-MS, Pt(II) release from nanocrystals under NIR irradiation (808 nm) in the presence of ascorbate was confirmed.…”

Section: Light-controlled Activation Of Pt(iv) Prodrugsmentioning

confidence: 99%

“…Moreover, two of the five mice in the group were tumor-free by the end of the experiment. Thus, the unique antitumor properties of the Pt(IV) nanoprodrug 12 modified with an erythrocyte-binding vector were shown by Wang et al [ 61 ].…”

Section: Light-controlled Activation Of Pt(iv) Prodrugsmentioning

confidence: 99%

Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs

Spector

Pavlov

Белоглазкина

et al. 2022

IJMS

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Pt(IV) prodrugs remain one of the most promising alternatives to conventional Pt(II) therapy due to their versatility in axial ligand choice and delayed mode of action. Selective activation from an external source is especially attractive due to the opportunity to control the activity of an antitumor drug in space and time and avoid damage to normal tissues. In this review, we discuss recent advances in photoabsorber-mediated photocontrollable activation of Pt(IV) prodrugs. Two main approaches developed are the focus of the review. The first one is the photocatalytic strategy based on the flavin derivatives that are not covalently bound to the Pt(IV) substrate. The second one is the conjugation of photoactive molecules with the Pt(II) drug via axial position, yielding dual-action Pt(IV) molecules capable of the controllable release of Pt(II) cytotoxic agents. Thus, Pt(IV) prodrugs with a light-controlled mode of activation are non-toxic in the absence of light, but show high antiproliferative activity when irradiated. The susceptibility of Pt(IV) prodrugs to photoreduction, photoactivation mechanisms, and biological activity is considered in this review.

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“…Certain Pt(IV) prodrugs, such as Pt(IV) with promising drug uptake capability via albumin binding, have been reported. , Certain Pt(IV) prodrugs could be activated by light, electricity, or a tumor microenvironment. Once activated, these prodrugs are able to selectively stimulate the release of Pt(II) complexes. − Other inhibitor-conjugated Pt(IV) prodrugs are designed to substitute the combination of inhibitors with platinum. − Therefore, Pt(IV) prodrugs are also known as next-generation platinum drugs and have now shown particular potential in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Pt(IV) Prodrug as a Potential Antitumor Agent with APE1 Inhibitory Activity

Yuan

et al. 2022

J. Med. Chem.

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The base excision repair (BER) pathway is essential for cancer cells to resist chemotherapeutic treatment, but its significance is underrated. The present study describes a novel Pt(IV) prodrug, AP1, targeting a critical BER protein, apurinic/apyrimidinic endonuclease 1 (APE1). AP1 induces intracellular accumulation of platinum and activates DNA damage response and apoptosis signals. AP1 can strongly inhibit the growth of malignant cells, including cisplatin-resistant cancer cells, with up to 18.11 times inhibition compared with cisplatin. Moreover, it is as toxic to normal cells as cisplatin. In a xenograft model, AP1 is 3.86-fold more potent than cisplatin without adverse effects. Intriguingly, AP1 can directly inhibit the AP endonuclease activity of APE1, leading to an interruption of miRNA processing and upregulation of the tumor suppressor PTEN. Our findings shed light on a mode of Pt(IV) interaction with a target protein and highlight the critical role of BER in platinum-based cancer treatment.

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An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response

Abstract: The outcome of conventional platinum (Pt)-based chemotherapy is limited by reduced circulation, failure to accumulate in the tumor, and dose-limiting toxicity arising from non-controllable activation. To address these limitations, we...

Cited by 20 publications

References 56 publications

Metallo-Drugs in Cancer Therapy: Past, Present and Future

Metallo-Drugs in Cancer Therapy: Past, Present and Future

Recent Advances in Light-Controlled Activation of Pt(IV) Prodrugs

Pt(IV) Prodrug as a Potential Antitumor Agent with APE1 Inhibitory Activity

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