ROS Responsive Nanoparticles Encapsulated with Natural Medicine Remodel Autophagy Homeostasis in Breast Cancer

Zhang, Xinhui; Hong, Gao; Wei, Daohe; Pei, Xiaoying; Zhang, Yue; Wang, Jian; Chang, Jin; Wu, Xiaoli

doi:10.1021/acsami.3c03068

Cited by 21 publications

(7 citation statements)

References 47 publications

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“…This might be attributed to the weaker lipophilicity of DSPE-PEG 2000 -OH compared with DSPE-PEG 2000 -OA-Tig, potentially leading to the formation of a hydration protective film on the nanoparticle surface, reducing cellular uptake . Moreover, increased ROS-activated tumor cell protective autophagy, which could be inhibited to starve cells, increased cell sensitivity, and improved uptake efficiency . Therefore, we speculate that the enhanced uptake described above may also be related to the ROS-responsive nature of DSPE-PEG 2000 -OA-Tig.…”

Section: Resultsmentioning

confidence: 96%

Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

Zou,

Sun,

et al. 2023

ACS Appl. Mater. Interfaces

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The increased risk of breast cancer metastasis is closely linked to the effects of platelets. Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this study, we devised an innovative system by combining cell membrane fusion liposomes (CML) loaded with the light-switchable transgene DTA (pDTA) and a ticagrelor (Tig) prodrug. This innovative system, named the sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML), aims to achieve targeted pDTA delivery while concurrently inhibiting platelet activity through the sequential release of Tig triggered by reactive oxygen species with the tumor microenvironment. In vitro investigations have indicated that pDTA-Tig@CML, with its ability to sequentially release Tig and pDTA, effectively suppresses platelet activity, resulting in improved therapeutic outcomes and the mitigation of platelet driven metastasis in breast cancer. Furthermore, pDTA-Tig@CML exhibits enhanced tumor aggregation and successfully restrains tumor growth and metastasis. It also reduces the levels of ADP, ATP, TGF-β, and P-selectin both in vitro and in vivo, underscoring the advantages of combining the bioactivating Tig prodrug nanoplatform with the LightOn system. Consequently, pDTA-Tig@CML emerges as a promising light-switchable DTA transgene system, offering a novel bioactivating prodrug platform for breast cancer treatment.

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Section: Resultsmentioning

confidence: 96%

Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

Zou,

Sun,

et al. 2023

ACS Appl. Mater. Interfaces

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“…Earlier works have shown that nanoparticles can be designed for autophagy induction via designed surface chemistry, 42−44 modular cytotoxicity, 39 modular ROS generation property, 45,46 and mitochondrial membrane damage property. 47 Here we have demonstrated that rapid cell uptake of the arginineterminated nanoparticle can lead to cellular ATP depletion and autophagy induction.…”

Section: Lowering Of Arginine Surface Density Shifts the Nanoparticle...mentioning

confidence: 99%

Arginine Surface Density of Nanoparticles Controls Nonendocytic Cell Uptake and Autophagy Induction

Ray,

Ghosh,

Maity

et al. 2024

ACS Appl. Mater. Interfaces

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Nonendocytic cell uptake of nanomaterials is challenging, which requires specific surface chemistry and smaller particle size. Earlier works have shown that an arginine-terminated nanoparticle of <10−20 nm size shows nonendocytic uptake via direct membrane penetration. However, the roles of surface arginine density and the argininearginine distance at the nanoparticle surface in controlling such nonendocytic uptake mechanism is not yet explored. Here we show that a higher arginine density at the nanoparticle surface with an arginine-arginine distance of <3 nm is the most critical aspect for such nonendocytic uptake. We have used quantum dot (QD)-based nanoparticles as a model for fluorescent tracking inside cells and for quantitative estimation of cellular uptake. We found that arginine-terminated nanoparticles of 10 nm size can opt for the energydependent endocytosis pathway if the arginine-arginine distance is >3 nm. In contrast, nanoparticles with <3 nm arginine-arginine distance rapidly enter into the cell via the nonendocytic approach, are freely available in the cytosol in large amounts to capture the cellular adenosine triphosphate (ATP), generate oxidative stress, and induce ATP-deficient cellular autophagy. This work shows that arginine-arginine distance at the nanoparticle surface is another fundamental parameter, along with the particle size, for the nonendocytic cell uptake of foreign materials and to control intracellular activity. This approach may be utilized in designing nanoprobes and nanocarriers with more efficient biomedical performances.

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“… 136 Similarly, Zhang X et al co-delivered photosensitizer aggregation induced emission (AIE) and autophagy inhibitor triptolide (TP) through (TP+A) @TkPEG nanoparticles to generate ROS by laser irradiation, and then TP inhibited the antioxidant pathway mediated by Nrf2, while inhibiting the protective autophagy, significantly enhancing the therapeutic efficacy in breast cancer. 137 Besides, Li N et al co-delivered photosensitizer CONs and autophagy inhibitor pTRPM2 through CONs/pTRPM2 nanoparticles, inhibiting autophagy by TRPM2-mediated Ca 2+ influx, significantly improving the efficacy of ROS mediated apoptosis in prostate cancer. 138 In addition, researchers pointed out that autophagy inhibition can significantly improve the efficiency of photothermal cancer therapy.…”

Section: Application Of Nanomedicine Combined With Autophagy Regulato...mentioning

confidence: 99%

Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors

Yang,

Ding,

Mao

et al. 2024

IJN

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The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment.

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ROS Responsive Nanoparticles Encapsulated with Natural Medicine Remodel Autophagy Homeostasis in Breast Cancer

Cited by 21 publications

References 47 publications

Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

Arginine Surface Density of Nanoparticles Controls Nonendocytic Cell Uptake and Autophagy Induction

Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors

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