Near-infrared photoactivatable semiconducting polymer nanocomplexes with bispecific metabolism interventions for enhanced cancer immunotherapy

Yu, Ningyue; Ding, Mengbin; Wang, Fengshuo; Zhou, Jianhui; Shi, Xiangyang; Cai, Rong; Li, Jingchao

doi:10.1016/j.nantod.2022.101600

Cited by 40 publications

(23 citation statements)

References 71 publications

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“…ROS‐cleavable linker with terminal carboxyl groups on each side was synthesized according to previous work. [ 7c ]…”

Section: Methodsmentioning

confidence: 99%

“…The evaluations of ATP, CRT, and HMGB1 levels in tumor tissues were conducted according to previous work. [ 7d ]…”

Section: Methodsmentioning

confidence: 99%

“…To address the concern of uncontrolled release of immunotherapeutic agents, activatable immunotherapeutic nanoparticles that can specifically unleash cargo upon response to different stimuli have been widely developed. [ 7 ] For example, a second near‐infrared (NIR‐II) photoactivatable organic polymer nanoparticle with conjugation of an A2AR antagonist has been reported to improve the efficacy and safety of photothermal‐immunotherapy. [ 8 ] Nevertheless, the applications of photoactivatable nanosystems are more suitable for superficial tumors as the tissue penetration depths are limited.…”

Section: Introductionmentioning

confidence: 99%

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Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors

et al. 2023

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Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual-cascade activatable nanopotentiator for sonodynamic therapy (SDT) and chemodynamic therapy (CDT)-cooperated immunotherapy of deep tumors via reshaping adenosine metabolism is herein reported. This nanopotentiator (NP MCA ) is constructed through crosslinking adenosine deaminase (ADA) with chlorin e6 (Ce6)-conjugated manganese dioxide (MnO 2 ) nanoparticles via a reactive oxygen species (ROS)-cleavable linker. In the tumor microenvironment with ultrasound (US) irradiation, NP MCA mediates CDT and SDT concurrently in deep tumors covered with 2-cm tissues to produce abundant ROS, which results in dual-cascade scissoring of ROS-cleavable linkers to activate ADA within NC MCA to block adenosine metabolism. Moreover, immunogenic cell death (ICD) of dying tumor cells and upregulation of the stimulator of interferon genes (STING) is triggered by the generated ROS and Mn 2+ from NP MCA , respectively, leading to activation of antitumor immune response. The potency of immune response is further reinforced by reducing the accumulation of adenosine in tumor microenvironment by the activated ADA. As a result, NP MCA enables CDT and SDT-cooperated immunotherapy, showing an obviously improved therapeutic efficacy to inhibit the growths of bilateral tumors, in which the primary tumors are covered with 2-cm tissues.

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“…ROS‐cleavable linker with terminal carboxyl groups on each side was synthesized according to previous work. [ 7c ]…”

Section: Methodsmentioning

confidence: 99%

“…The evaluations of ATP, CRT, and HMGB1 levels in tumor tissues were conducted according to previous work. [ 7d ]…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors

et al. 2023

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“…PDT is a promising approach for cancer therapy through generating ROS. − In addition to directly inducing cell death, the generated ROS during PDT can destroy ROS-responsive elements in gene carriers to achieve controlled gene delivery in targeted sites, thus regulating gene expression.…”

Section: Photodynamic Regulation Of Gene Expressionmentioning

confidence: 99%

Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression

et al. 2023

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Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.

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“…Light-responsive nanosystems provide a powerful tool for specific delivery of drugs into target sites. − These nanosystems enable on-demand release of cargos upon the stimulation by light and thus display high selectivity and specificity . Ultraviolet/visible light are generally utilized for causing the release of drugs from photoresponsive nanosystems, while their limited tissue penetrating ability and potential phototoxicity should be concerned. − Near-infrared (NIR) light showing much greater tissue penetration depths and negligible damages to normal tissues have been adopted to achieve controlled drug release. − Currently, NIR light-responsive nanosystems have been extensively explored for precision cancer therapy. − Therefore, specific delivery of metastasis inhibitors to targeting sites using NIR light-responsive nanosystems should be a promising strategy for effective tumor metastasis, which however has been poorly reported.…”

Section: Introductionmentioning

confidence: 99%

Inhibitor-Decorated Nanoscale Semiconducting Polymer Prodrugs for Photodynamically Amplified Chemotherapy and Metastasis Inhibition

Cheng

Zhang

et al. 2022

ACS Appl. Nano Mater.

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Although photodynamic therapy (PDT) can be adopted for treating malignant tumors, the therapeutic outcome is dissatisfactory due to the hypoxia state of solid tumors and tumor metastasis after treatment. To conquer these issues, the preparation of nanoscale semiconducting polymer prodrugs with decoration of a metastasis inhibitor for photodynamic-amplified chemotherapy and metastasis inhibition is reported. The inhibitordecorated semiconducting polymer nanoprodrugs (SPN ST ) are formed through nanoprecipitation of a semiconducting polymer, metastasis inhibitor (SIS3), and hypoxia-responsive prodrug (tirapazamine, TPZ) in the presence of a singlet oxygen ( 1 O 2 )cleavable amphiphilic polymer. In the tumor sites with accumulation of nanoparticles, SPN ST produce 1 O 2 via PDT effect under near-infrared (NIR) laser irradiation, leading to apoptosis of partial tumor cells and destruction of 1 O 2 -cleavable amphiphilic polymers for light-activated release of SIS3 and TPZ. The hypoxia of tumors is aggravated due to oxygen consumption during PDT, triggering the activation of TPZ into a toxic form for chemotherapy, which results in photodynamic-amplified chemotherapy. Moreover, the released SIS3 can inhibit the metastasis of tumor cells into lungs. As a result, SPN ST exhibit an enhanced efficacy for treating subcutaneous 4T1 tumors and suppressing lung metastasis. Thus, this study reports an NIR photoresponsive drug delivery nanosystem for simultaneous effective treatment of hypoxic tumor and metastasis inhibition.

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Near-infrared photoactivatable semiconducting polymer nanocomplexes with bispecific metabolism interventions for enhanced cancer immunotherapy

Cited by 40 publications

References 71 publications

Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors

Dual‐Cascade Activatable Nanopotentiators Reshaping Adenosine Metabolism for Sono‐Chemodynamic‐Immunotherapy of Deep Tumors

Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression

Inhibitor-Decorated Nanoscale Semiconducting Polymer Prodrugs for Photodynamically Amplified Chemotherapy and Metastasis Inhibition

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