A camptothecin prodrug induces mitochondria-mediated apoptosis in cancer cells with cascade activations

Luo, Xiangjie; Chi, Xiaoqin; Lin, Yaying; Yang, Zhaoxuan; Lin, Hongyu; Gao, Jinhao

doi:10.1039/d1cc04379j

Cited by 20 publications

(18 citation statements)

References 24 publications

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“…The thioketal linkage is one important ROS-cleavable linkage, ROS-cleavable thioketal linker is supposed to undergo an intramolecular nucleophilic substitution and then form a five-membered ring thiolactone after the 1 O 2 deprotection reaction, and releasing protected chemotherapy drugs. [19][20][21] But the intrinsic ROS concentration in the body is too low to cleave it, photosensitizer irradiated by laser can efficiently generate ROS to cleave the thioketal linkage, which can markedly [14] Copyright 2021 Elsevier. (C) The structure of BP 20 -DCM-SCPT.…”

Section: Light-activated Prodrugs With Pdt Activitymentioning

confidence: 99%

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Advances in Multifunctional Chemotherapeutic Prodrugs for Near‐infrared Fluorescence Imaging‐guided Therapy

Zeng

Liu

et al. 2023

ChemBioChem

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Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor‐targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near‐infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real‐time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo‐drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging‐guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging‐guided therapy are provided.

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Section: Light-activated Prodrugs With Pdt Activitymentioning

confidence: 99%

Section: Light-activated Prodrugs With Pdt Activitymentioning

confidence: 99%

Advances in Multifunctional Chemotherapeutic Prodrugs for Near‐infrared Fluorescence Imaging‐guided Therapy

Zeng

Liu

et al. 2023

ChemBioChem

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“…Among the TI category and in the field of anticancer nanomedicines, the natural drug camptothecin (CTP) (see Section 4.4 ) is particularly appealing to be modified and synthetized in the form of prodrugs, often in combination with PSs [ 149 , 150 , 151 ], and to be further utilized for the formation of carrier-free NPs [ 152 , 153 ]. As an example, Chu and co-workers reported on the synthesis of a novel ROS-responsive nanosystem (MPEG-(TK-CPT)-PPa) derived from the self-assembly of a prodrug of CPT and pyropheophorbide (PPa) both conjugated to a PEG methyl ether (MPEG) via a TK and lipid linkage, respectively [ 109 ].…”

Section: Drug Delivery Systems For Pss and Chemotherapeutics: An Over...mentioning

confidence: 99%

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage

Menilli

Milani

Reddi

et al. 2022

Cancers

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The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models.

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“…It inhibits DNA synthesis in cancer cells via inhibiting DNA topoisomerase I, leading to the apoptosis of tumor cells [2,23] . Recently, researchers delivered CPT to mitochondria and achieved satisfactory antitumor efficiency [2,24–26] …”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species‐Responsive Peptide‐Drug Conjugate for Mitochondria‐Specific Chemotherapy

Cheng

et al. 2022

ChemNanoMat

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Chemotherapy is one of the main means in clinical cancer treatment, but the efficient and precise delivery of chemotherapeutic drugs remains a key bottleneck. The precise delivery of nanomedicines to the mitochondria may achieve unexpected therapeutic effect, and peptides are considered as a promising class of mitochondrial targeting molecules. In this paper, we reported a reactive oxygen species (ROS)-responsive peptide-drug conjugate (PDC, CPT-TK-KLAK) self-delivery system, where a mitochondria-targeted peptide (KLAK, sequence: (KLAKLAK) 2 ) is linked to the anticancer drug camptothecin (CPT) via a ROS responsive unit. The release amount of CPT from CPT-TK-KLAK in the 1 mM H 2 O 2 solution was ca. 90% in 24 h, while CPT-CC-KLAK barely released CPT in 1 mM H 2 O 2 solution. Therefore, after targeting to the mitochondria of HeLa cells, CPT-TK-KLAK can specifically release CPT under overproduced ROS, which in turn destroys mitochondria and induces ROS burst, causing HeLa cells apoptosis. As a result, CPT-TK-KLAK exhibits high cytotoxicity to HeLa cells with an IC 50 of 0.37 μM, which is 9fold lower than free CPT. This ROS-responsive PDC can also be applied for the targeted delivery of other chemotherapeutic agents, thereby enhancing therapeutic efficacy.

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A camptothecin prodrug induces mitochondria-mediated apoptosis in cancer cells with cascade activations

Abstract: Mitochondria are crucial regulators of the intrinsic pathway of apoptosis. Herein, we report a photosensitizer-conjugated camptothecin (CPT)-based prodrug for combinative chemo-photodynamic treatment of solid tumors with cascade activations. Upon light...

Cited by 20 publications

References 24 publications

Advances in Multifunctional Chemotherapeutic Prodrugs for Near‐infrared Fluorescence Imaging‐guided Therapy

Advances in Multifunctional Chemotherapeutic Prodrugs for Near‐infrared Fluorescence Imaging‐guided Therapy

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage

Reactive Oxygen Species‐Responsive Peptide‐Drug Conjugate for Mitochondria‐Specific Chemotherapy

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