An intelligent cell-selective polymersome-DM1 nanotoxin toward triple negative breast cancer

Zhang, Yifan; Yue, Shujing; Haag, Rainer; Sun, Huanli; Zhong, Zhiyuan

doi:10.1016/j.jconrel.2021.11.014

Cited by 23 publications

(20 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…637 polymer chains in each polymersome. 38 By facilely adding DM1 in the course of assembly, N 3 -P-DM1 with covalently conjugated DM1 via disulfide linkages can be conveniently prepared in a relatively large scale. In brief, 2.23 mL of DM1 solution (10 mg/mL) in N,N-dimethylformamide (DMF) was added into 93 mL of phosphate buffer (PB, 10 mM, pH 7.4) and stirred at 37 °C, followed by continuous injection of 200 mg of polymers dissolved in 5 mL of DMF.…”

Section: Methodsmentioning

confidence: 99%

“…Here, PBS-treated mice were shared with our another work. 38 Tumor length (L) and width (W) were measured every 2 days using calipers to calculate the tumor volumes (V = 0.5 × L × W 2 ). Body weights of mice were recorded every 2 days and compared to their initial data on day 0.…”

Section: Methodsmentioning

confidence: 99%

“…36,37 DM1 can be facilely and covalently conjugated to the polymersomal membrane via disulfide linkage. 38,39 Notably, by incorporating azide-functionalized PEG-P(TMC-DTC) into the polymersomes, cetuximab can be engineered at their surface via click chemistry. C-P-DM1 represents an innovative EGFR-specific nanotoxin that elegantly combines the advantages of ADCs and nanomedicines for treating TNBC and NSCLC tumors.…”

Section: Introductionmentioning

confidence: 99%

“…Herein, we developed a robust cetuximab–polymersome–DM1 nanodrug (C-P-DM1) with high drug to antibody ratio (DAR), minimum DM1 leakage, and glutathione (GSH)-triggered DM1 release for highly potent and targeted therapy of EGFR-positive solid tumors in vivo (Scheme ). The polymersomes based on poly(ethylene glycol)- b -poly(trimethylene carbonate- co -dithiolane trimethylene carbonate) [PEG-P(TMC-DTC)] have shown a high stability owing to disulfide crosslinking of the membrane. , DM1 can be facilely and covalently conjugated to the polymersomal membrane via disulfide linkage. , Notably, by incorporating azide-functionalized PEG-P(TMC-DTC) into the polymersomes, cetuximab can be engineered at their surface via click chemistry. C-P-DM1 represents an innovative EGFR-specific nanotoxin that elegantly combines the advantages of ADCs and nanomedicines for treating TNBC and NSCLC tumors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cetuximab–Polymersome–Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers

et al. 2021

Self Cite

View full text Add to dashboard Cite

Targeted nanomedicines particularly armed with monoclonal antibodies are considered to be the most promising advanced chemotherapy for malignant cancers; however, their development is hindered by their instability and drug leakage problems. Herein, we constructed a robust cetuximab−polymersome−mertansine nanodrug (C-P-DM1) for highly potent and targeted therapy of epidermal growth factor receptor (EGFR)-positive solid tumors. C-P-DM1 with a tailored cetuximab surface density of 2 per P-DM1 exhibited a size of ca. 60 nm, high stability with minimum DM1 leakage, glutathione-triggered release of native DM1, and 6.0−11.3-fold stronger cytotoxicity in EGFR-positive human breast (MDA-MB-231), lung (A549), and liver (SMMC-7721) cancer cells (IC 50 = 27.1−135.5 nM) than P-DM1 control. Notably, intravenous injection of C-P-DM1 effectively repressed subcutaneous MDA-MB-231 breast cancer and orthotopic A549-Luc lung carcinoma in mice without inducing toxic effects. Strikingly, intratumoral injection of C-P-DM1 completely cured 60% of mice bearing breast tumor without recurrence. This robust cetuximab−polymersome−mertansine nanodrug provides a promising new strategy for targeted treatment of EGFR-positive solid malignancies.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cetuximab–Polymersome–Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Drug/antibody ratio could be heightened more easily simply by regulating primary feed ratio. To date, several kinds of antibodies have been utilized to develop polymersome‐based targeted delivery system, including anti‐EGFR antibody (cetuximab, trastuzumab) (Lale et al, 2015; Liu et al, 2014; Yue et al, 2021), anti‐CD44 antibody (Zhang et al, 2021), Anti‐PSCA antibody (Ling et al, 2011) and anti‐EpCAM antibody (Chen et al, 2015). Since antibodies are unstable in critical conditions and will be inactivated in some organic solvents, they are mostly conjugated to polymersomes after the self‐assembly process.…”

Section: Intelligent Design Of Polymersomes For Improved Cancer Therapymentioning

confidence: 99%

Intelligent design of polymersomes for antibacterial and anticancer applications

Wang

Qin

Cheng

et al. 2022

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Polymersomes (or polymer vesicles) have attracted much attention for biomedical applications in recent years because their lumen can be used for drug delivery and their coronas and membrane can be modified with a variety of functional groups. Thus, polymersomes are very suitable for improved antibacterial and anticancer therapy. This review mainly highlighted recent advances in the synthetic protocols and design principles of intelligent antibacterial and anticancer polymersomes. Antibacterial polymersomes are divided into three categories: polymersomes as antibiotic nanocarriers, intrinsically antibacterial polymersomes, and antibacterial polymersomes with supplementary means including photothermal and photodynamic therapy. Similarly, the anticancer polymersomes are divided into two categories: polymersomes-based delivery systems and anticancer polymersomes with supplementary means. In addition, the bilateral relationship between bacteria and cancer is addressed, since more and more evidences show that bacteria may cause cancer or promote cancer progression. Finally, prospective on next-generation antibacterial and anticancer polymersomes are discussed.

show abstract

Nanoparticle‐Mediated STING Activation for Cancer Immunotherapy

et al. 2023

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway has attracted much attention because of the secretion of various proinflammatory cytokines and chemokines. Many STING agonists have been identified and applied into preclinical or clinical trials for cancer immunotherapy. However, the fast excretion, low bioavailability, nonspecificity, and adverse effects of the small molecule STING agonists limit their therapeutic efficacy and in vivo application. Nanodelivery systems with appropriate size, charge, and surface modification are capable of addressing these dilemmas. In this review, the mechanism of the cGAS-STING pathway is discussed and the STING agonists, focusing on nanoparticle-mediated STING therapy and combined therapy for cancers, are summarized. Finally, the future direction and challenges of nano-STING therapy are expounded, emphasizing the pivotal scientific problems and technical bottlenecks and hoping to provide general guidance for its clinical application.

show abstract

An intelligent cell-selective polymersome-DM1 nanotoxin toward triple negative breast cancer

Cited by 23 publications

References 47 publications

Cetuximab–Polymersome–Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers

Cetuximab–Polymersome–Mertansine Nanodrug for Potent and Targeted Therapy of EGFR-Positive Cancers

Intelligent design of polymersomes for antibacterial and anticancer applications

Nanoparticle‐Mediated STING Activation for Cancer Immunotherapy

Contact Info

Product

Resources

About