Engineering of Amphiphilic Erlotinib Analogue as Novel Nanomedicine for Non-Small Cell Lung Cancer Therapy DOI Creative Commons

Mei Cong,

Houjun Pang,

Guangxing Xie

et al.

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 6367 - 6377

Published: Nov. 1, 2023

Purpose: Molecular targeted therapy is one of the most pivotal strategies in treatment non-small cell lung cancer, yet its curative effect severely compromised by poor aqueous solubility, low bioavailability and inadequate tumor accumulation agents. To enhance efficacy agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment. Methods: An composed hydrophobic hydrophilic biotin block was synthesized characterized nuclear magnetic resonance (NMR) well high-resolution mass spectrometry (HRMS). Then, nanoassemblies molecules are formulated using nanoprecipitation method. Subsequently, size, morphology, uptake, anticancer activity vivo distribution newly constructed were systematically assessed some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, imaging system etc. Results: We developed nanoformulation erlotinib, which possesses high drug loading 45%. With features well-defined structure small obtained could be effectively accumulated sites rapidly internalized cancer cells. Finally, erlotinib-based showed considerably better compared to free both vitro vivo. Moreover, displayed great tolerability. Conclusion: Combining advantageous nanotechnology self-assemble, this nanomedicine constitutes promising therapeutic candidate This study also underlines potential use improving reducing toxicity, become general strategy preparation nanodrugs active Keywords: molecule, self-assembling, self-delivery system,

Language: Английский

Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System DOI Creative Commons
Weiran Ma, Xiaoying Wang, Dongqi Zhang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 7547 - 7566

Published: July 1, 2024

Abstract: Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, narrow therapeutic window, unfavorable pharmacokinetic properties. To solve above problems, target drug delivery tumor cells, reduce side effects drugs, an anti-tumor system based on microenvironment has become focus research in recent years. The construction reduction-sensitive nanomedicine disulfide bonds attracted much attention. Disulfide good reductive responsiveness can effectively high glutathione (GSH) levels environment, enabling precise delivery. further enhance targeting accelerate release, are often combined with pH-responsive nanocarriers highly expressed ligands cells construct systems. connect molecules polymer system, as well between different carrier molecules. This article summarized systems (DDS) that researchers constructed years bond microenvironment, cleavage-triggering conditions, various loading strategies, design. In this review, we also discuss controlled release mechanisms these DDS clinical applicability challenges faced translation. Keywords: bond, systems, GSH/ROS

Language: Английский

Citations

18
Research Progress of SN38 Drug Delivery System in Cancer Treatment DOI Creative Commons

Qing-rui Qi,

Huan Tian,

Baosen Yue

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 945 - 964

Published: Jan. 1, 2024

Abstract: The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN38), is 100– 1000 times more than CPT-11 and has shown inhibitory effects on a range cancer cells, including those from the rectal, small cell lung, breast, esophageal, uterine, ovarian malignancies. Despite SN38's potent anticancer properties, its hydrophobicity pH instability have caused substantial side activity loss, which make it difficult to use in clinical settings. To solve above problems, construction SN38-based drug delivery systems one most feasible methods improve solubility, enhance stability, increase targeting ability, bioavailability, therapeutic efficacy reduce adverse reactions. Therefore, based mechanism systems, this paper reviews SN38 polymeric micelles, liposomal nanoparticles, protein conjugated targeted by aptamers ligands, antibody-drug couplings, magnetic targeting, photosensitive redox-sensitive multi-stimulus-responsive co-loaded systems. focus review nanocarrier-based We hope provide reference for translation application novel medications. Keywords: SN38, system,

Language: Английский

Citations

13
Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol DOI
C. Pan, Chi Zhang, Zonghan Lin

et al.

Combinatorial Chemistry & High Throughput Screening, Journal Year: 2024, Volume and Issue: 27(11), P. 1611 - 1628

Published: Jan. 12, 2024

Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related disulfidptosis, a newly discovered cell death mechanism, remains unclear.

Language: Английский

Citations

6
Preparation and Antitumor Activity of Reduction-sensitive Pre-drug Micelles Loaded with Paclitaxel DOI
Yu Yang,

Lixin Fan,

Chunling Gao

et al.

Colloids and Surfaces A Physicochemical and Engineering Aspects, Journal Year: 2025, Volume and Issue: unknown, P. 136376 - 136376

Published: Feb. 1, 2025

Language: Английский

Citations

0
Carrier-free nano-prodrugs for enhanced cancer therapy: stimuli-responsive design and applications DOI
Yoshitaka Koseki

Polymer Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

Citations

0
Facile synthesis and polymerization of 1,4,5-oxadithiepan-2-one for disulfide-based redox-responsive drug delivery DOI
Debojit Chakraborty, Anindita Sengupta, Jayanta Bhattacharyya

et al.

Polymer, Journal Year: 2024, Volume and Issue: 298, P. 126920 - 126920

Published: March 18, 2024

Language: Английский

Citations

3
HSA-nanobinders crafted from bioresponsive prodrugs for combined cancer chemoimmunotherapy–an in vitro exploration DOI Creative Commons
Matilde Tubertini, Luca Menilli, Celeste Milani

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: March 27, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype of still lacking effective treatment options. Chemotherapy in combination with immunotherapy can restrict tumor progression and repolarize the microenvironment towards anti-tumor milieu, improving clinical outcome TNBC patients. The chemotherapeutic drug paclitaxel has been shown to induce immunogenic cell death (ICD), whereas inhibitors indoleamine 2,3- dioxygenase 1 (IDO1) enzyme, whose expression shared immune regulatory cells, have revealed enhance response. However, poor bioavailability pharmacokinetics, off-target effects hurdles achieving therapeutic concentrations at target tissue often limit effectiveness therapies. This work describes development novel biomimetic carrier-free nanobinders (NBs) loaded both IDO1 inhibitor NLG919 form bioresponsive prodrugs. A fine tuning preparation conditions allowed identify NB@5 as most suitable nanoformulation terms reproducibility, stability vitro effectiveness. Our data show that effectively binds HSA cell-free experiments, demonstrating its protective role controlled release drugs suggesting potential exploit protein endogenous vehicle for targeted delivery site. study successfully proves encapsulated within NBs are preferentially released under altered redox commonly found microenvironment, thereby inducing death, promoting ICD, inhibiting IDO1.

Language: Английский

Citations

2
Structural Modification Endows Small-Molecular SN38 Derivatives with Multifaceted Functions DOI Creative Commons

Yi Dai,

Qian Meng,

Yan Li

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(13), P. 4931 - 4931

Published: June 22, 2023

As a camptothecin derivative, 7-ethyl-10-hydroxycamptothecin (SN38) combats cancer by inhibiting topoisomerase I. SN38 is one of the most active compounds among derivatives. In addition, also theranostic reagent due to its intrinsic fluorescence. However, poor water solubility, high systemic toxicity and limited action against drug resistance metastasis tumor cells indicates that there great space for structural modification SN38. From perspective chemical modification, this paper summarizes progress in improving increasing activity, reducing possessing multifunction analyzes strategies structure provide reference development based on

Language: Английский

Citations

5
Deciphering the Comprehensive Structure–Activity Relationship of Sunshinamide for Breast Cancer Therapy through Dual Modulation of Apoptotic and Ferroptotic Pathways via TrxR1 and Gpx4 Inhibition DOI

Akash Chatterjee,

Joyanta Mondal, Subhojit Paul

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Sunshinamide, a cyclodepsipeptide, has demonstrated significant potential in inhibiting cancer cell proliferation. Our prior research established the total synthesis and anticancer properties of sunshinamide. However, deeper understanding structure–activity relationship (SAR) sunshinamide remained imperative. In this study, we aimed to elucidate SAR mechanistic insights underlying action, both vitro vivo. studies confirm crucial roles bicyclic-ring disulfide moiety activity recent findings unveil that targets TrxR1, leading ROS generation ER-stress-mediated apoptosis, while also promoting lipid peroxidation by targeting Gpx4, rendering cells vulnerable ferroptosis. vivo, experiments effectiveness reducing tumor growth inducing apoptosis The dual efficacy eliciting ferroptosis positions it as promising candidate for breast therapy, addressing challenge chemoresistance.

Language: Английский

Citations

1
Advances in the treatment of pancreatic cancer with traditional Chinese medicine DOI Creative Commons

Zhang Yan-hua,

Hui Xu,

Yue Li

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 7, 2023

Pancreatic cancer is a common malignancy of the digestive system. With high degree and poor prognosis, it called “king cancers.” Currently, Western medicine treats pancreatic mainly by surgical resection, radiotherapy, chemotherapy. However, curative effect not satisfactory. The application Traditional Chinese Medicine (TCM) in treatment has many advantages becoming an important facet comprehensive clinical treatment. In this paper, we review current therapeutic approaches for cancer. We also protective effects shown TCM different models discuss potential molecular mechanisms these.

Language: Английский

Citations

2