Enhanced photodynamic therapy for overcoming tumor hypoxia: From microenvironment regulation to photosensitizer innovation

Du, Jianjun; Shi, Tiancong; Long, Saran; Chen, Pengzhong; Sun, Wen; Fan, Jiangli; Peng, Xiaojun

doi:10.1016/j.ccr.2020.213604

Cited by 131 publications

(66 citation statements)

References 120 publications

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“…However,t he hypoxic microenvironment of solid tumor (pO 2 < 5mmHg) severely reduces the therapeutic effect of Ty pe-II PSs in PDT because such treatment is heavily dependent on O 2 concentration. [18][19][20][21] This has been recognized as am ajor bottleneck of PDT in the clinical transformation. [22] Unfortunately,r apid O 2 consumption and vascular damage during the type-II PDT further worsen its shortage.…”

Section: Introductionmentioning

confidence: 99%

BODIPY‐Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen

et al. 2021

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Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy(PDT) for hypoxic tumors.However,it remains ac hallenge to design photosensitizers for generating reactive oxygen species by the Type-I process.H erein, we report aseries of a,b-linked BODIPY dimers and atrimer that exclusively generate superoxider adical (O 2 À C)b yt he Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S 1 )t ot riplet (T 1 )s tates via an intermediate triplet (T 2 )s tate.T he lowr eduction potential and ultralong lifetime of the T 1 state facilitate the efficient generation of O 2 À C by inter-molecular charge transfer to molecular oxygen. The energy gap of T 1 -S 0 is smaller than that between 3 O 2 and 1 O 2 therebyp recluding the generation of singlet oxygen by the Type-II process.T he trimer exhibits superior PDT performance under the hypoxic environment.

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Section: Introductionmentioning

confidence: 99%

BODIPY‐Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen

et al. 2021

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“…[ 82 ] In particular, the TME presents a physiological environment different from normal tissues with lower O 2 content, lower pH, vascular abnormality, immunosuppressive features and higher interstitial pressures. [ 199 ] All these characteristics are normal impede effectiveness in tumor therapy. Specially, the lack of O 2 can severely restrict the efficacy of O 2 ‐dependent treatments such as PDT.…”

Section: Reversing Tme To Relieve Hypoxiamentioning

confidence: 99%

Conquering the Hypoxia Limitation for Photodynamic Therapy

et al. 2021

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Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due to the hypoxic nature characteristic of many solid tumors, PDT is frequently limited in therapeutic effect. Moreover, the consumption of O2 during PDT may further aggravate the tumor hypoxic condition, which promotes tumor proliferation, metastasis, and invasion resulting in poor prognosis of treatment. Therefore, numerous efforts have been made to increase the O2 content in tumor with the goal of enhancing PDT efficacy. Herein, these strategies developed in past decade are comprehensively reviewed to alleviate tumor hypoxia, including 1) delivering exogenous O2 to tumor directly, 2) generating O2 in situ, 3) reducing tumor cellular O2 consumption by inhibiting respiration, 4) regulating the TME, (e.g., normalizing tumor vasculature or disrupting tumor extracellular matrix), and 5) inhibiting the hypoxia‐inducible factor 1 (HIF‐1) signaling pathway to relieve tumor hypoxia. Additionally, the O2‐independent Type‐I PDT is also discussed as an alternative strategy. By reviewing recent progress, it is hoped that this review will provide innovative perspectives in new nanomaterials designed to combat hypoxia and avoid the associated limitation of PDT.

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“…However, free Hb with a very short circulation time and poor stability in vivo will cause severe side effects in patients. Therefore, chemical conjugation or physical encapsulation is usually adopted to modify free Hb to overcome these shortcomings [ 39–41 ] Platelet (PLT) membrane with excellent biocompatibility and tumor targetability is identified as one of the best options. Xia et al.…”

Section: O2 Carrier Strategiesmentioning

confidence: 99%

Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials

Jin

Zhao

Yuan

et al. 2021

Macromolecular Bioscience

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Hypoxia as one of the most prominent features in tumors, has presented negative effects on tumor therapies including photodynamic therapy, radiotherapy, and chemotherapies, leading to the tumor regeneration and metastasis. Recently, nanomedicines have been proposed to handle the hypoxia dilemma. Some nanomedicines alleviated hypoxia to enhance the therapeutic effect, others used hypoxia‐sensitive substances to treat tumor. Among them, macromolecular nanomaterials‐based nanomedicine has attracted increased research interest. However, the complicated tumor microenvironment disturbs the practical application of macromolecular nanomaterials to deal with hypoxia. This review highlights the influence of hypoxia on tumor therapy and some new strategies of using macromolecular nanomaterials to overcome hypoxia for effective tumor therapy.

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Enhanced photodynamic therapy for overcoming tumor hypoxia: From microenvironment regulation to photosensitizer innovation

Cited by 131 publications

References 120 publications

BODIPY‐Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen

BODIPY‐Based Photodynamic Agents for Exclusively Generating Superoxide Radical over Singlet Oxygen

Conquering the Hypoxia Limitation for Photodynamic Therapy

Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials

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