Molecular recognition-driven supramolecular nanoassembly of a hydrophobic uracil prodrug and hydrophilic cytarabine for precise combination treatment of solid and non-solid tumors

Li, Chang; Wang, Qiu; Li, Dan; Liu, Yubo; Hu, Baichun; Yao, Feng; Zhang, Haotian; Zhang, He; Luo, Cong; Sun, Jin

doi:10.1039/d1nh00590a

Cited by 11 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They can also pass through the BBB into the brain tissues, inhibiting acetylcholinesterase [ 32 ]. Additionally, uracil conjugates with pharmacophores, such as DOX, and demonstrates promising outcomes in terms of cancer cell selectivity and targeted drug delivery [ 33 , 34 , 35 ]. Polyvinyl alcohol (PVA) was applied as an additional emulsifier of the nanoemulsion due to such characteristics as biodegradability, biocompatibility, and nontoxicity [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells

et al. 2023

View full text Add to dashboard Cite

Brain tumor glioblastoma is one of the worst types of cancer. The blood–brain barrier prevents drugs from reaching brain cells and shields glioblastoma from treatment. The creation of nanocarriers to improve drug delivery and internalization effectiveness may be the solution to this issue. In this paper, we report on a new nanocarrier that was developed to deliver the anticancer drug doxorubicin to glioblastoma cells. The nanocarrier was obtained by nanoemulsion polymerization of diallyl disulfide with 1-allylthymine. Diallyl disulfide is a redox-sensitive molecule involved in redox cell activities, and thymine is a uracil derivative and one of the well-known bioactive compounds that can enhance the pharmacological activity of doxorubicin. Doxorubicin was successfully introduced into the nanocarrier with a load capacity of about 4.6%. Biological studies showed that the doxorubicin nanocarrier composition is far more cytotoxic to glioblastoma cells (T98G) than it is to cancer cells (M-HeLa) and healthy cells (Chang liver). The nanocarrier improves the penetration of doxorubicin into T98G cells and accelerates the cells’ demise, as is evident from flow cytometry and fluorescence microscopy data. The obtained nanocarrier, in our opinion, is a promising candidate for further research in glioblastoma therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Cytarabine (Ara-C), a milestone chemotherapeutic agent, has been applied for the treatment of acute myeloid leukemia (AML) and other hematological malignancies over the past few decades . It can also be used for better of solid tumors in combination with other anticancer agents due to its rapid blood clearance. , In recent studies, Ara-C has been reported to possess immunomodulatory properties instead of the direct induction of anticancer immune responses, , suggesting that the immunological potential of Ara-C can be utilized as a means of promoting antitumor immunity in conjunction with other therapeutics, such as PDT. However, to date, to our knowledge, there is no report of the combination of Ara-C and photosensitizers for chemo-photodynamic therapy and subsequent immune responses.…”

Section: Introductionmentioning

confidence: 99%

Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

Tian

Zhang

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for cancer therapy. In this study, we designed a carrier-free chemophotodynamic nanoplatform (A-C/NPs) using a co-assembly strategy with cytarabine (Ara-C) and chlorin e6 (Ce6) to induce pyroptosis and a subsequent immune response against breast cancer. Mechanistically, A-C/NPs can trigger GSDMEmediated pyroptosis in a controllable manner through reactive oxygen species (ROS) accumulation, causing immunogenic cell death (ICD), in which dying cells release high-mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and calcitonin (CRT). Additionally, Ara-C can stimulate the maturation of cytotoxic T lymphocytes to act synergistically with Ce6-mediated immunogenic cell death (ICD), collectively augmenting the anticancer effect of A-C/NPs. The A-C/NPs showed excellent suppressive effects on the growth of orthotopic, abscopal, and recurrent tumors in a breast cancer mouse model. The chemo-photodynamic therapy (PDT) using the proposed nanomedicine strategy could be a novel strategy for triggering pyroptosis and improving the global anticancer immune response.

show abstract

“…[46] Yet, despite the expansion of various strategies to design H-bonded biomaterials, the investigation of nanomedicine within such platform opposing the ordering effects via H-bonding forces is a newly emerging and extremely promising field. [47][48][49] Considering their outstanding potential in clinical research and translation, H-bonded nanomedicine has attracted the growing attention from synthetic chemists, materials scientists, biologists and physicians. [50] Several outstanding reviews have been reported in the field of supramolecular nanotheranostics.…”

Section: Introductionmentioning

confidence: 99%

“…[ 46 ] Yet, despite the expansion of various strategies to design H‐bonded biomaterials, the investigation of nanomedicine within such platform opposing the ordering effects via H‐bonding forces is a newly emerging and extremely promising field. [ 47–49 ]…”

Section: Introductionmentioning

confidence: 99%

Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

Chen

Lortie

et al. 2022

Macromol. Rapid Commun.

View full text Add to dashboard Cite

Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug-and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.

show abstract

Molecular recognition-driven supramolecular nanoassembly of a hydrophobic uracil prodrug and hydrophilic cytarabine for precise combination treatment of solid and non-solid tumors

Abstract: The reduction sensitive supramolecular nanoassembly was based on U-SS-DOX and Ara-C specific molecular recognition. The drug release in the supramolecular nanoassembly was triggered and controlled in tumor cells with low pH and excessive GSH.

Cited by 11 publications

References 30 publications

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells

Thymine-Modified Nanocarrier for Doxorubicin Delivery in Glioblastoma Cells

Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

Contact Info

Product

Resources

About