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

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

doi:10.1021/acs.biomac.1c01065

Cited by 13 publications

(10 citation statements)

References 67 publications

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“…Nanoparticles functionalized with specific molecules such as proteins [ 42 ], antibodies [ 43 ], RNA [ 44 ] may modulate pharmacokinetics and targeting recognition, and increase the efficacy of targeted drugs [ 17 , 45 ]. Cet is a specific EGFR antibody for clinical cancer therapy [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Lin

Raj

et al. 2022

Pharmaceutics

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Nanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo. The optimal fluorescent intensities of ND particles were observed in the human lung cancer cells and nude mice under in vivo imaging system. The fluorescence signal of ND particles can be real-time detected in the xenografted human lung tumor formation of nude mice. Moreover, the ND-conjugated specific EGFR antibody cetuximab (Cet) can track the location and distribution of EGFR proteins of lung cancer cells in vitro and in vivo. ND-Cet treatment increased cellular uptake ability of nanocomposites in the EGFR-expressed cells but not in the EGFR-negative lung cancer cells. Interestingly, single ND-Cet complex can be directly observed on the protein G bead by immunoprecipitation and confocal microscopy. Besides, the EGFR proteins were transported to lysosomes for degradation. Together, this study demonstrates that ND-conjugated Cet can apply for targeting EGFR and monitoring tumorigenesis during lung cancer progression and therapy.

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Section: Discussionmentioning

confidence: 99%

“…However, EGFR mutations did not disturb the sensitivity of Cet on targeting EGFR [ 48 , 49 ]. A range of EGFR-targeted nanoparticles has been engineered via tethering the Cet [ 43 , 50 , 51 ]. In this study, ND-Cet can target EGFR in lung cancer with or without EGFR mutations.…”

Section: Discussionmentioning

confidence: 99%

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Lin

Raj

et al. 2022

Pharmaceutics

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“…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%

“…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. Yue and co‐workers reported a cetuximab‐conjugated mertansine‐encapsulated polymersome nanocarrier (Yue et al, 2021). As shown in Figure 8b, mertansine is an anticancer drug; cetuximab is an anti‐EGFR antibody which can target epidermal growth factor receptors overexpressed in cancer cells.…”

Section: Intelligent Design Of Polymersomes For Improved Cancer Therapymentioning

confidence: 99%

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Intelligent design of polymersomes for antibacterial and anticancer applications

Wang

Qin

Cheng

et al. 2022

WIREs Nanomed Nanobiotechnol

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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.

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Fabrication of GSH‐Responsive Poly(Tertiary Amine‐Oxide)‐Based Nanomedicines for Enhanced Anticancer Drug Release

Zhang,

Ma,

Wang

et al. 2023

Macro Chemistry & Physics

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Poly(tertiary amine‐oxide)‐based polymeric nanocarriers have showed more functionalities than stealthy PEG‐based analogs due to the structure of phospholipid affinitive N‐oxides groups, which has attracted considerable attention to the synthesis of various zwitterionic copolymers with tertiary amine‐oxide grafts for enhanced anticancer drug delivery. However, poly(tertiary amine‐oxide)‐based amphiphilic copolymers with tumor intracellular microenvironment sensitivities, to the knowledge, have been rarely reported likely due to the lack of a controlled synthetic strategy. Herein, a reducible zwitterionic copolymer, poly(ε‐caprolactone)25‐SS‐poly(2‐(N‐oxide‐N,N‐diethylamino)ethyl methacrylate)30 (PCL25‐SS‐OPDEA30) is designed and synthesized successfully via combination of controlled polymerization techniques and post polymerization modification. Specifically, postoxidation of poly(tertiary amine) is confirmed to be a better synthetic strategy toward a well‐defined polymer structure relative to direct polymerization of N,N‐diethylaminoethyl methacrylate (ODEA). The effect of disulfide bridges on the self‐assembly behaviors, in vitro drug loading and drug release properties is investigated in detail. Notablely, the resulting micelles self‐assembled from PCL25‐SS‐OPDEA30 show much greater colloidal stability, higher drug loading content (DLC), and better in vitro tumor cell inhibition than the reduction‐insensitive counterparts. Overall, this study reports a robust strategy toward zwitterionic nanomedicines for on‐demand anticancer drug delivery.

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

Cited by 13 publications

References 67 publications

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Intelligent design of polymersomes for antibacterial and anticancer applications

Fabrication of GSH‐Responsive Poly(Tertiary Amine‐Oxide)‐Based Nanomedicines for Enhanced Anticancer Drug Release

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