Magnolol-loaded cholesteryl biguanide conjugate hydrochloride nanoparticles for triple-negative breast cancer therapy

Wang, Yanzhi; Sun, Cancan; Huang, Leaf; Liu, Mengqian; Li, Lü; Wang, Linchao; Sun, Shanshan; Xu, Haiwei; Ma, Gege; Zhang, Lei; Zheng, Jiaxin; Liu, Hong‐Min

doi:10.1016/j.ijpharm.2022.121509

Cited by 14 publications

(10 citation statements)

References 52 publications

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“…Additionally, free PHE demonstrated concentration-dependent cytotoxicity against 3T3-L1 cells with fewer cells attached by the end of the experiment, and the cell morphology became smaller and spherical with floating lipids (Figure S10). The CS-PHE conjugates demonstrated dramatically reduced cytotoxicity while retaining the therapeutic efficacy of PHE (Figures c,e, and S10), perhaps due to the cell compatibility of CS, the organelle-specific transport of CS-PHE (Figure e), and the presence of biguanide moieties . At lower concentrations, such as 1 mM, CS-PHE was proven to stimulate adipogenesis ( P < 0.001), whereas, at higher concentrations (2.5–10 mM), CS-PHE dramatically inhibited adipogenesis in 3T3-L1 adipocytes (Figure c,e).…”

Section: Resultsmentioning

confidence: 97%

“…The CS-PHE conjugates demonstrated dramatically reduced cytotoxicity while retaining the efficacy of PHE (Figures 5c,e and S10), possibly due to the impact of CS, 54 the organelle-specific transport of CS-PHE (Figure 3e), and the presence of biguanide moieties. 43 As an AMPK activator, PHE inhibits Complex I of the respiratory chain and induces apoptosis of WATs. 66,67 The cell death observed in PHE-treated 3T3-L1 cells might be related to the inhibition of Complex I, whereas CS-PHE micelles were proven to be much less cytotoxic in 3T3-L1 cells than PHE, possibly due to the reduced distribution to the mitochondria (Figure 3e).…”

Section: Discussionmentioning

confidence: 99%

“…The CS-PHE conjugates demonstrated dramatically reduced cytotoxicity while retaining the therapeutic efficacy of PHE (Figures 5c,e, and S10), perhaps due to the cell compatibility of CS, 54 the organelle-specific transport of CS-PHE (Figure 3e), and the presence of biguanide moieties. 43 such as 1 mM, CS-PHE was proven to stimulate adipogenesis (P < 0.001), whereas, at higher concentrations (2.5−10 mM), CS-PHE dramatically inhibited adipogenesis in 3T3-L1 adipocytes (Figure 5c,e). Additionally, 5 mM CS-PHE was capable of inhibiting lipid accumulation (P < 0.01), and the inhibitory effect was enhanced in a concentration-dependent manner (Figure 5e).…”

Section: Cs-phe Micelles and Coadministration With Cs-pbe/clt Micelle...mentioning

confidence: 95%

“…42 However, biguanides are proven to be an essential family of antidiabetic drugs, and the biguanide moiety is critical to its efficacy. 43 In our study, a facile CS and PHE conjugate was synthesized via an amide linkage that retains the structure of biguanide while rendering the conjugate with amphiphilicity, targetability, and efficacy. The positively charged PHE contains a biguanide structure, which may impact the uptake behavior of CS-PHE.…”

Section: Introductionmentioning

confidence: 99%

“…Previously used for type II diabetes, PHE has now been withdrawn in many countries due to fatal lactic acidosis . However, biguanides are proven to be an essential family of antidiabetic drugs, and the biguanide moiety is critical to its efficacy . In our study, a facile CS and PHE conjugate was synthesized via an amide linkage that retains the structure of biguanide while rendering the conjugate with amphiphilicity, targetability, and efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

Niu,

Gao,

Ouyang

et al. 2024

ACS Appl. Bio Mater.

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Adipose tissue macrophages (ATMs) are crucial in maintaining a low-grade inflammatory microenvironment in adipose tissues (ATs). Modulating ATM polarization to attenuate inflammation represents a potential strategy for treating obesity with insulin resistance. This study develops a combination therapy of celastrol (CLT) and phenformin (PHE) using chondroitin sulfate-derived micelles. Specifically, CLT-loaded 4-aminophenylboronic acid pinacol ester-modified chondroitin sulfate micelle (CS-PBE/CLT) and chondroitin sulfate-phenformin conjugate micelles (CS-PHE) were synthesized, which were shown to actively target ATs through CD44-mediated pathways. Furthermore, the dual micellar systems significantly reduced inflammation and lipid accumulation via protein quantification and Oil Red O staining. In preliminary in vivo studies, we performed H&E staining, immunohistochemical staining, insulin tolerance test, and glucose tolerance test, and the results showed that the combination therapy using CS-PBE/CLT and CS-PHE micelles significantly reduced the average body weight, white adipose tissue mass, and liver mass of high-fat diet-fed mice while improving their systemic glucose homeostasis. Overall, this combination therapy presents a promising alternative to current treatment options for diet-induced obesity.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Cs-phe Micelles and Coadministration With Cs-pbe/clt Micelle...mentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

Niu,

Gao,

Ouyang

et al. 2024

ACS Appl. Bio Mater.

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The development of nanocarriers for natural products

Huang,

Luo,

Tong

et al. 2024

WIREs Nanomed Nanobiotechnol

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Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier‐based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self‐assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long‐term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety.This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Enhancing anti-tumor therapy with agmatine-cholesterol conjugate liposomes: in vitro and in vivo evidence

Wang,

Chang

et al. 2023

Drug Deliv. and Transl. Res.

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In this study, we synthesized a novel compound, agmatine-cholesterol conjugate (AG-Chol), to enhance the anti-tumor activity of liposomes. We used AG-Chol to replace cholesterol in preparing doxorubicin hydrochloride (DOX) liposomes by an active loading method. We assessed the physical and chemical properties of the resulting liposomes (AG-Liposomes) and evaluated their e cacy in vitro and in vivo. The results showed that AG-Liposomes were stable with high encapsulation e ciency. Compared with the control liposomes, AG-Liposomes exhibited a slower release rate in the release medium at pH 6.8. The in vitro cell experiments demonstrated that AG-Liposomes had higher tumor cell uptake, migration inhibition rate, apoptosis rate, anti-clonogenic ability, and lysosome escape ability than the control liposomes. In vivo distribution results demonstrate that liposomes prepared with AG-Chol instead of cholesterol can signi cantly enhance their tumor targeting abilities and reduce their distribution to non-targeted sites. In vivo tumor suppression experiments showed that AG-Liposomes had a higher tumor suppression rate than the control liposomes without apparent toxicity, as evidenced by histological staining. Therefore, substituting cholesterol with AG-Chol in the preparation of liposomes can result in enhanced lysosome escape, improved tumor targeting, and increased e cacy of anti-tumor drugs.

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Magnolol-loaded cholesteryl biguanide conjugate hydrochloride nanoparticles for triple-negative breast cancer therapy

Cited by 14 publications

References 52 publications

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

Chondroitin Sulfate-Derived Micelles for Adipose Tissue-Targeted Delivery of Celastrol and Phenformin to Enhance Obesity Treatment

The development of nanocarriers for natural products

Enhancing anti-tumor therapy with agmatine-cholesterol conjugate liposomes: in vitro and in vivo evidence

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