How can we use the endocytosis pathways to design nanoparticle drug-delivery vehicles to target cancer cells over healthy cells?

Cong, Vu Thanh; Houng, Jacinta; Kavallaris, Maria; Chen, Xin; Tilley, Richard D.; Gooding, J. Justin

doi:10.1039/d1cs00707f

Cited by 52 publications

(32 citation statements)

References 218 publications

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“…2e). Receptor-mediated endocytosis was mostly performed through clathrin or caveolin pathway 31,32 and we used chlorpromazine (clathrin-mediated endocytosis inhibitor) and lipin (caveolin-mediated endocytosis inhibitor) to investigate the exact mechanism of RLP internalization. Filipin signi cantly inhibited SIRPα endocytosis while chlorpromazine had little effect, suggesting that SIRPα-mediated RLP internalization was mainly through caveolin pathway after CD47-SIRPα interaction and cell membrane invagination (Fig.…”

Section: Resultsmentioning

confidence: 99%

Checkpoint Nano-degrader to Transiently Promote Efferocytosis in Acute Myocardial Infarction

Gao

Huang

Wang

et al. 2023

Preprint

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The efferocytosis of apoptotic cardiomyocytes (CMs) after acute myocardial infarction (AMI) is required for inflammation resolution and cardiac repair. However, this process would be impaired by the interaction of elevated CD47 on apoptotic CMs with receptor signal-regulatory protein alpha (SIRPα) on macrophages. Herein, based on receptor-mediated internalization, we developed senescent RBC-mimetic liposome (RLP) as a nano-degrader to promote SIRPα degradation and inhibit CD47-SIRPα axis transiently. After injection, we demonstrated that RLP modified with Ly6G antibody hitchhiked neutrophiles and was released to macrophages in the border area of the infarct heart, which was subsequently internalized by macrophages through SIRPα and degraded in lysosome. CD47-SIRPα axis blockade consequently facilitated the efferocytosis of apoptotic CMs and lead to decreased infarct area and anti-inflammatory microenvironment for improved cardiac remodeling. This nano-degrader presents a practical membrane protein degradation strategy to transiently inhibit CD47-SIRPα axis and boost apoptotic CMs efferocytosis.

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Section: Resultsmentioning

confidence: 99%

Checkpoint Nano-degrader to Transiently Promote Efferocytosis in Acute Myocardial Infarction

Gao

Huang

Wang

et al. 2023

Preprint

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“…It is critical to design an in vivo delivery system that could “turn off” the internalization function in the circulation and non‐tumor tissues, but “turn on” in the tumor, which needs to utilize the special tumor microenvironment. [ 18 ] Previous studies have proven that the imidazole group (pKa≈6) of histidine undergoes a shift from neutral to cationic in the mildly acidic tumor microenvironment. [ 19 ] This change in charge neutralizes the negative charge of the CSS, thereby releasing the electrostatic interactions with cationic residues of the SCP.…”

Section: Resultsmentioning

confidence: 99%

A Versatile Platform for the Tumor‐Targeted Intracellular Delivery of Peptides, Proteins, and siRNA

Yang

Zhu

Liu

et al. 2023

Adv Funct Materials

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The efficient delivery of biologics into cells provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. The supercharged polypeptide (SCP) has become a novel intracellular delivery system due to their special advantages, including enhanced delivery efficiency and serum tolerance. However, owing to their cationic charge and non‐specificity characteristics, the in vivo application of SCP is limited. Here, an activatable SCP (ASCP) with a pH‐sensitive charge shielding sequence (CSS), a protease cleavage site, and SCP are engineered. This system shows the potential to reduce the non‐specific binding and effectively deliver various cargo (peptide, protein, small molecule, and siRNA) into the cytosol not only in vitro but also in vivo. Furthermore, an ASCP fusion protein is designed to co‐delivery of peptide (KLA)/siRNA (IKBKE) with different tumorigenesis pathways to triple negative breast cancer (TNBC) for optimal therapeutic outcomes. It is believed that ASCP delivery system will facilitate the development of bioactive molecules for use against intracellular targets. This simple yet versatile delivery system can also pave the way for the co‐delivery of multiple therapeutic cargos to address the emerging needs of combination cancer therapy.

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“…Nano boyuttaki taşıyıcı sistemlerin kimyasal, fiziksel veya biyolojik özellikleri nedeniyle hastalıklardan korunma, hastalıkların teşhis ve tedavisinde kullanımları giderek önem kazanmaktadır [1][2][3][4][5][6][7][8]. Nanopartiküler sistemler sayesinde, ilacın spesifik organlara, hücrelere ve hatta hücresel organellere hedeflendirilmesi, istenilen düzeyde ve süre boyunca etkin madde salımı sağlanarak ilacın etkinliği artırılmakta ve aynı zamanda yan etkiler en aza indirilmektedir [9][10][11][12].…”

Section: Introductionunclassified

Nanopartiküler İlaç Taşıyıcı Sistemlerinin İncelenmesinde Kullanılan İn Vitro Salım Testi Yöntemlerine Genel Bir Bakış

ÇOBANOGLU

Şenel

2023

HUJPHARM

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Bir ilacın dozaj şeklinden salım özelliklerinin incelenmesinde kullanılan in vitro salım testi sayesinde hem ilacın in vitro yararlanımı hakkında bilgi edinilmesi hem de diğer ürünlerle eşdeğerliğinin karşılaştırması mümkün olmaktadır. Doğru ve güvenilir sonuçlar elde edilmesi için uygun salım testi yönteminin ve uygun salım koşullarının (sıcaklık, salım ortamı, pH, karıştırma /akış hızı vb.) seçilmesi esastır. Farmakopelerde birçok dozaj şekli için in vitro salım testi yöntemleri ve koşulları tanımlanmış olmasına karşın hâlihazırda nanopartiküler ilaç taşıyıcı sistemler için bir test yöntemi farmakopelerde mevcut değildir. Bu derlemede, nanopartiküler sistemlerden ilaç salımının incelenmesinde kullanılan test yöntemleri (örnek alma ve ayırma, membran difüzyon, sürekli akış vb.) ve güncel uygulamalarından bahsedilecek ve birbirlerine olan üstünlükleri ve sakıncaları tartışılacaktır.

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How can we use the endocytosis pathways to design nanoparticle drug-delivery vehicles to target cancer cells over healthy cells?

Abstract: Targeted drug delivery in cancer typically focuses on maximising the endocytosis of drugs into the diseased cells.

Cited by 52 publications

References 218 publications

Checkpoint Nano-degrader to Transiently Promote Efferocytosis in Acute Myocardial Infarction

Checkpoint Nano-degrader to Transiently Promote Efferocytosis in Acute Myocardial Infarction

A Versatile Platform for the Tumor‐Targeted Intracellular Delivery of Peptides, Proteins, and siRNA

Nanopartiküler İlaç Taşıyıcı Sistemlerinin İncelenmesinde Kullanılan İn Vitro Salım Testi Yöntemlerine Genel Bir Bakış

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