A dual-response drug delivery system with X-ray and ROS to boost the anti-tumor efficiency of TPZ <i>via</i> enhancement of tumor hypoxia levels

Han, Panli; Zhang, Lianxue; Fu, Yanwei; You-yu, FU; Huang, Jianxiang; He, Jinlin; Ni, Peihong; Khan, Taimoor; Jiao, Yang; Yang, Zaixing; Zhou, Ruhong

doi:10.1039/d2nr04021b

Cited by 5 publications

(3 citation statements)

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“…However, the dose-dependent toxicity of TPZ was shown in the hypoxic environment. In fact, TPZ can be activated by various intracellular reductases to produce cytotoxic free radical intermediate [ 1 ], which tends to be oxidized rapidly into the non-toxic parent molecule in the presence of O 2 . Whereas in the absence of O 2 , the highly reactive TPZ free radicals snatch hydrogen atoms from the biomacromolecules around them and lead to structural damage of cells.…”

Section: Resultsmentioning

confidence: 99%

“…Cancer is still a major problem plaguing human life and health. The therapeutic efficacy of traditional treatment methods, such as chemotherapy, radiotherapy and surgery, are still not satisfactory, and the side effects are more damaging to the human body [ [1] , [2] , [3] ]. The development of treatment strategies that can effectively induce tumor cell death is a goal that people have been pursuing.…”

Section: Introductionmentioning

confidence: 99%

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Liposome encapsulated polydopamine nanoparticles: Enhancing ferroptosis and activating hypoxia prodrug activity

Guo,

Luo,

Jiang

et al. 2024

Materials Today Bio

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Liposome encapsulated polydopamine nanoparticles: Enhancing ferroptosis and activating hypoxia prodrug activity

Guo,

Luo,

Jiang

et al. 2024

Materials Today Bio

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“…Interestingly, feedback from many experimental data elaborated that most systems can indeed notably reduce the side effects aroused by the off-target of free drugs. [4][5][6][7][8][9] Nevertheless, they usually only showed a very limited treatment benefit. [3,[10][11][12] A major reason is the underestimation of the influence of aberrant tumor stromal microenvironments (TSMs) on NP transportation.…”

Section: Introductionmentioning

confidence: 99%

A pH‐responsive nanoparticle delivery system containing dihydralazine and doxorubicin‐based prodrug for enhancing antitumor efficacy

Zhang,

Huang,

Buratto

et al. 2023

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The efficacy of nanoparticle (NP)‐based drug delivery technology is hampered by aberrant tumor stromal microenvironments (TSMs) that hinder NP transportation. Therefore, the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance. Herein, we propose a potential solution using a dihydralazine (HDZ)‐loaded nanoparticle drug delivery system containing a pH‐responsive, cyclic RGD peptide‐modified prodrug based on doxorubicin (cRGD‐Dex‐DOX). With a combined experimental and theoretical approach, we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues. HDZ can notably downregulate the expression levels of hypoxia‐inducible factor 1α (HIF1α), α‐smooth muscle actin, and fibronectin through the dilation of tumor blood vessels. These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors, suggesting that such a system may offer an effective “multifunctional therapy” through both improving the chemotherapeutic effect and enhancing the immune response to tumors. In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens, with the lowest side effects as well.

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Enhancing X‐Ray Sensitization with Multifunctional Nanoparticles

Liu,

Wu,

Chen

et al. 2024

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In the progression of X‐ray‐based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

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A dual-response drug delivery system with X-ray and ROS to boost the anti-tumor efficiency of TPZ via enhancement of tumor hypoxia levels

Abstract: The selective anti-tumor activity and less toxic nature of hypoxia-activated pro drugs including tirapazamine (TPZ) is harbored by hypoxic insufficiency in tumors leading to failure in clinical trials. Thus, the...

Cited by 5 publications

References 46 publications

Liposome encapsulated polydopamine nanoparticles: Enhancing ferroptosis and activating hypoxia prodrug activity

Liposome encapsulated polydopamine nanoparticles: Enhancing ferroptosis and activating hypoxia prodrug activity

A pH‐responsive nanoparticle delivery system containing dihydralazine and doxorubicin‐based prodrug for enhancing antitumor efficacy

Enhancing X‐Ray Sensitization with Multifunctional Nanoparticles

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