Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

Xiao, Yong; Li, Xun; Mao, Jiahui; Zheng, Hong; Ji, Rui; Wang, Zhice; Guo, Mengyu; Xu, Jiyu; Anwar, Arfidin; Chen, Chunying; Liu, Xingjun; Liu, Jing

doi:10.1039/d2nr02064e

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…As it has been confirmed that Cela can play an apoptosis inducing role in a variety of tumor cells (Medatwal et al., 2020 ; Xiao et al., 2022 ), Annexin V/PI staining was adopted to evaluate the apoptosis-inducing effect of free Cela and C-TL/HA on HepG2 cells. As shown in Figure 5D , the apoptosis rate of C-TL/HA group was significantly higher than that of free Cela group ( p < 0.001), indicating that the enhanced proapoptotic effect of C-TL/HA might be related to the higher cellular uptake of Cela and the effective initiation of apoptosis induced by mitochondrial pathway.…”

Section: Resultsmentioning

confidence: 99%

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery

et al. 2023

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In order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo , but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy.

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Section: Resultsmentioning

confidence: 99%

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery

et al. 2023

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“… 14 , 15 In order to improve antitumor efficacy, there is an increasing emphasis on combination therapy, ie, the use of two or more drugs with different therapeutic mechanisms to enhance antitumor efficacy through synergistic effects. 16 , 17 The efficacy of free drug combinations is usually compromised by insufficient bioavailability, and nanocarrier co-delivery systems are potentially advantageous in combination therapy. To date, many nanosystems have been proposed to deliver two or more molecules with synergistic pharmacological activity to different cellular targets in the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

“…To date, many nanosystems have been proposed to deliver two or more molecules with synergistic pharmacological activity to different cellular targets in the tumor microenvironment. 16 , 17 For example, small dendritic macromolecules loaded with adriamycin (PAMAM-ss-DOX) (DP) were synthesized and encapsulated into pH-responsive nanoliposomes along with adjuvants toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and losartan (LOS). 18 Among them, LOS effectively reduced the activity of CAF.…”

Section: Introductionmentioning

confidence: 99%

Efficient Sequential Co-Delivery Nanosystem for Inhibition of Tumor and Tumor-Associated Fibroblast-Induced Resistance and Metastasis

Li,

Wang,

Zhang

et al. 2024

IJN

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Purpose Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them. Methods Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model. Results In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies. Conclusion Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.

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“…[ 42–44 ] Recent research found that advanced catalytic nanomaterials (including nanozymes) not only have the characteristics of high drug payload, low toxicity, good biocompatibility, and specific drug delivery through passive (enhanced permeability and retention, EPR) or active targeting but also own the capability of continuous releasing NO through catalytic reaction, which might significantly increase the feasibility of NO‐based therapies. [ 45–48 ] Within this context, there have been many efforts in designing and fabricating NO‐releasing platforms based on catalytic nanomaterials, and therefore, significant progress has been achieved in many biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Functional Nanomaterials for Catalytic Generation of Nitric Oxide: A Mini Review

Wang

Gan

et al. 2023

Small

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As a gaseous second messenger, nitric oxide (NO) plays an important role in a series of signal pathways. Research on the NO regulation for various disease treatments has aroused wide concern. However, the lack of accurate, controllable, and persistent release of NO has significantly limited the application of NO therapy. Profiting from the booming development of advanced nanotechnology, a mass of nanomaterials with the properties of controllable release have been developed to seek new and effective NO nano‐delivery approaches. Nano‐delivery systems that generate NO through catalytic reactions exhibit unique superiority in terms of precise and persistent release of NO. Although certain achievements have been made in the catalytically active NO delivery nanomaterials, some basic but critical issues, such as the concept of design, are of low attention. Herein, an overview of the generation of NO through catalytic reactions and the design principles of related nanomaterials are summarized. Then, the nanomaterials that generate NO through catalytic reactions are classified. Finally, the bottlenecks and perspectives are also discussed in depth for the future development of catalytical NO generation nanomaterials.

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Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

Abstract: CNPs synthesized by a simple and convenient method without involve any nano-carrier and toxicity organic solvent. Meanwhile, the functional CNPs with chitosan could be endocytosed by their nano-characterization to realize drug resistance reversal.

Cited by 12 publications

References 33 publications

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery

The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery

Efficient Sequential Co-Delivery Nanosystem for Inhibition of Tumor and Tumor-Associated Fibroblast-Induced Resistance and Metastasis

Recent Advances in Functional Nanomaterials for Catalytic Generation of Nitric Oxide: A Mini Review

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