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Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

ABSTRACT: The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.

SUBMITTER: Hao Y

PROVIDER: S-EPMC7578901 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

Hao Ying Y Chen Yuwen Y He Xinlong X Yu Yongyang Y Han Ruxia R Li Yang Y Yang Chengli C Hu Danrong D Qian Zhiyong Z

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200906 20

The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ...[more]

PMID: 33101874

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Project description:The combination of chemotherapy and photodynamic therapy (PDT) based on nanoparticles (NPs) has been extensively developed to improve the therapeutic effect and decrease the systemic toxicity of current treatments. However, overexpressed glutathione (GSH) in tumor cells efficiently scavenges singlet oxygens (1O2) generated from photosensitizers and results in the unsatisfactory efficacy of PDT. To address this obstacle, here we design H2O2-responsive polymer prodrug NPs with GSH-scavenger (Ce6@P(EG-a-CPBE) NPs) for chemo-photodynamic synergistic cancer therapy. They are constructed by the co-self-assembly of photosensitizer chlorin e6 (Ce6) and amphiphilic polymer prodrug P(EG-a-CPBE), which is synthesized from a hydrophilic alternating copolymer P(EG-a-PD) by conjugating hydrophobic anticancer drug chlorambucil (CB) via an H2O2-cleavable linker 4-(hydroxymethyl)phenylboronic acid (PBA). Ce6@P(EG-a-CPBE) NPs can efficiently prevent premature drug leakage in blood circulation because of the high stability of the PBA linker under the physiological environment and facilitate the delivery of Ce6 and CB to the tumor site after intravenous injection. Upon internalization of Ce6@P(EG-a-CPBE) NPs by tumor cells, PBA is cleaved rapidly triggered by endogenous H2O2 to release CB and Ce6. Ce6 can effectively generate abundant 1O2 under 660 nm light irradiation to synergistically kill cancer cells with CB. Concurrently, PBA can be transformed into a GSH-scavenger (quinine methide, QM) under intracellular H2O2 and prevent the depletion of 1O2, which induces the cooperatively strong oxidative stress and enhanced cancer cell apoptosis. Collectively, such H2O2-responsive polymer prodrug NPs loaded with photosensitizer provide a feasible approach to enhance chemo-photodynamic synergistic cancer treatment. Graphical abstract Schematic diagram of the H2O2-responsive P(EG-a-CPBE) prodrug with GSH-scavenger to encapsulate Ce6 for enhanced chemo-photodynamic synergistic cancer therapy.Image 1 Highlights • Polymer prodrug P(EG-a-CPBE) was synthesized by conjugating the chemodrug CB to the hydrophilic alternating copolymer P(EG-a-PD) via a H2O2-cleavable linker 4-(hydroxymethyl)phenylboronic acid (PBA).• H2O2-responsive P(EG-a-CPBE) prodrug with GSH-scavenger was used to encapsulate photosensitizer Ce6 to form the Ce6@P(EG-a-CPBE) NPs for chemo-photodynamic synergistic cancer therapy.• Upon irradiation by 660 nm laser, the Ce6@P(EG-a-CPBE) NPs showed superior synergistic therapeutic effect and excellent biosafety.

Dataset Information

Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

Publications

Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

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