Peptide-modified bioresponsive chondroitin sulfate micelles for targeted doxorubicin delivery in triple-negative breast cancer

Wang, Liangliang; Ling, Yun; Xiao, Xia; Gong, Jianfeng; Jin, Hongguang; Xu, Jing; Chen, P.; Xie, Xin; Zhang, Lei

doi:10.1016/j.colsurfb.2023.113381

Cited by 11 publications

(4 citation statements)

References 60 publications

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“…The clinical application of nanoplatforms has been restricted due to significant concerns regarding their toxicity. 71 In order to address this issue, three major parameters, including body weight changes, pathological toxicity, and systematic distribution of treatment agents, were analyzed to assess the toxicity and biosafety of candidate formulations in immunocompromised C57BL/6 mice. Throughout the treatments, no significant weight loss was observed in all experimental groups (Fig.…”

Section: Resultsmentioning

confidence: 99%

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents

Iranpour,

Bahrami,

Dayyani

et al. 2024

J. Mater. Chem. B

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Section: Resultsmentioning

confidence: 99%

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents

Iranpour,

Bahrami,

Dayyani

et al. 2024

J. Mater. Chem. B

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“…We hypothesize that our drug 9S1R-NulloPT targets mitochondrial ATP production and ribosome biogenesis leading to a loss of metabolic activity of the cells. To ensure more efficient killing of these aggressive TNBC cells in vivo and to enable tumor size reduction, we plan to use our drug synergistically along with other anticancer drugs that act through different cytotoxic pathways [ 58 – 61 ].…”

Section: Discussionmentioning

confidence: 99%

Nullomer peptide increases immune cell infiltration and reduces tumor metabolism in triple negative breast cancer mouse model

Ali

Wolf

Kanchan

et al. 2023

Preprint

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Background Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group of species. Primes are those nullomers that have not been detected in the genome of any species. 9S1R is a 5-aa peptide derived from a prime sequence that is tagged with 5 arginine aa, used to treat triple negative breast cancer (TNBC) in an in vivo TNBC mouse model. 9S1R is administered in trehalose (9S1R-NulloPT), which enhances solubility and exhibits some independent effects against tumor growth and is thus an important component in the drug preparation. Method We examined the effect of 9S1R-NulloPT on tumor growth, metabolism, metastatic burden, necrosis, tumor immune microenvironment, and the transcriptome of aggressive mouse TNBC tumors. Results The peptide-treated mice had smaller tumors in the initial phase of the treatment, as compared to the untreated control, and reduced in vivo bioluminescence at later stages, which is indicative of metabolically inactive tumors. A decrease in ex vivo bioluminescence was also observed in the excised tumors of treated mice, but not in the secondary metastasis in the lungs. The treatment also caused changes in tumor immune microenvironment with increased infiltration of immune cells and margin inflammation. The treatment upregulated 365 genes and downregulated 710 genes in tumors compared to the untreated group. Consistent with in vitro findings in breast cancer cell lines, downregulated genes in the treated TNBC tumors include Cellular Metabolic Process Related genes (179), specifically mitochondrial genes associated with TCA cycle/oxidative phosphorylation (44), and translation machinery/ribosome biogenesis genes (45). Among upregulated genes, the Developmental Pathway (13), ECM Organization (12) and Focal Adhesion Related Pathways (7) were noteworthy. We also present data from a pilot study using a bilateral BC mouse model, which supports our findings. Conclusion In conclusion, although 9S1R-NulloPT was moderate at reducing the tumor volume, it altered the tumor immune microenvironment as well as the tumor transcriptome, rendering tumors metabolically less active by downregulating the mitochondrial function and ribosome biogenesis. This corroborates previously published in vitro findings.

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“…Designing nanomicelles with targeting effect can solve the problem of toxic side effects of DOX on normal tissues and cells in the treatment of TNBC. For example, Yu et al ( Yu J et al, 2023 ) prepared a high drug loading micelle (C-TCSSD-DOX) with a targeted peptide (CDVEWVDVS) grafted with chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and loaded with DOX ( Figure 4A ). The DOX in the drug-loaded micelles was rapidly released in a release medium containing 20 mM of GSH, the cumulative release rate could reach 73.8% ± 3.11% at 96 h. The reason was the introduction of disulfide bonds in the system, under the stimulation of high GSH in the tumor site, the disulfide bonds were broken, the rapid release of DOX in the tumor cells exerted the anti-tumor effect.…”

Section: Novel Nano-drug Delivery Systemsmentioning

confidence: 99%

Section: Novel Nano-drug Delivery Systemsmentioning

confidence: 99%

Advances in Doxorubicin-based nano-drug delivery system in triple negative breast cancer

Zeng,

Luo,

Gan

et al. 2023

Front. Bioeng. Biotechnol.

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Triple positive breast cancer (TPBC) is one of the most aggressive breast cancer. Due to the unique cell phenotype, aggressiveness, metastatic potential and lack of receptors or targets, chemotherapy is the choice of treatment for TNBC. Doxorubicin (DOX), one of the representative agents of anthracycline chemotherapy, has better efficacy in patients with metastatic TNBC (mTNBC). DOX in anthracycline-based chemotherapy regimens have higher response rates. Nano-drug delivery systems possess unique targeting and ability of co-load, deliver and release chemotherapeutic drugs, active gene fragments and immune enhancing factors to effectively inhibit or kill tumor cells. Therefore, advances in nano-drug delivery systems for DOX therapy have attracted a considerable amount of attention from researchers. In this article, we have reviewed the progress of nano-drug delivery systems (e.g., Nanoparticles, Liposomes, Micelles, Nanogels, Dendrimers, Exosomes, etc.) applied to DOX in the treatment of TNBC. We also summarize the current progress of clinical trials of DOX combined with immune checkpoint inhibitors (ICIS) for the treatment of TNBC. The merits, demerits and future development of nanomedicine delivery systems in the treatment of TNBC are also envisioned, with the aim of providing a new class of safe and efficient thoughts for the treatment of TNBC.

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Peptide-modified bioresponsive chondroitin sulfate micelles for targeted doxorubicin delivery in triple-negative breast cancer

Cited by 11 publications

References 60 publications

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents

Nullomer peptide increases immune cell infiltration and reduces tumor metabolism in triple negative breast cancer mouse model

Advances in Doxorubicin-based nano-drug delivery system in triple negative breast cancer

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