Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: An intelligent tumor-targeted delivery nanoplatform

Huang, Yushu; Zhang, Wanli; Xu, Yanyun; Zhu, Shulei; Wu, Yanqian; Chen, Tiandong; Xiao, Yi; Lü, Wei; Zhang, Xiongwen; Yu, Jiahui

doi:10.1016/j.ijpharm.2020.119250

Cited by 17 publications

(8 citation statements)

References 43 publications

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“…This enabled superior internalization of loaded doxorubicin into the cell nuclei and consequent dislodgement of target cells from spheroids. Premature drug release during transport through the tumor interstitium can be avoided by designing micellar formulations capable of dissociating under tumor-relevant conditions, as demonstrated in [ 11 ]. Here, PBA was linked with the shell-forming block, whereas the drug was attached to the core-forming counterpart using reduction-sensitive thiol linkage.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

et al. 2020

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This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14–20 nm) which remained stable against temperature (ca. 25–45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π–π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

et al. 2020

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“…As a natural product, Camptothecin (CPT) is derived from Camptotheca acuminata and exhibits anti‐cancer activity by inhibiting topoisomerase I, which causes DNA damage 150 . Although CPT has significant tumour inhibition ability, it is too hydrophobic to be soluble in water, which limits its further clinical application 151 . By designing a novel pH‐activatable CPP, LHHLLHHLHHLLHH‐NH 2(LH), the conjugate showed more significant pH‐dependent anti‐cancer activity than free CPT after binding CPT to LH 152 …”

Section: Cpps and Anti‐cancer Cargoes Deliverymentioning

confidence: 99%

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Zhou

Zou

Cheng

et al. 2022

Clinical & Translational Med

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Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti‐cancer drugs are severely restricted from reaching the tumour site. Cell‐penetrating peptides (CPPs) are typically made up of 5–30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti‐cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs‐based drug delivery strategy could be improved by clever design or chemical modifications to develop the next‐generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

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“…Moreover, studies showed that treatment with different CPT prodrugs (CCLM and RGD-prodrug) led to tumor elimination and suppressing tumor progression and growth in HepG2 and H22 tumor-bearing mice [ 109 , 110 ]. These prodrug nano-platforms showed considerable in vivo anticancer efficacy, without displaying considerable systemic toxicity.…”

Section: Anticancer Activities Of Camptothecin Nano-formulationsmentioning

confidence: 99%

Recent Advances in Improved Anticancer Efficacies of Camptothecin Nano-Formulations: A Systematic Review

Ghanbari-Movahed

Kaceli

Mondal³

et al. 2021

Biomedicines

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Camptothecin (CPT), a natural plant alkaloid, has indicated potent antitumor activities via targeting intracellular topoisomerase I. The promise that CPT holds in therapies is restricted through factors that include lactone ring instability and water insolubility, which limits the drug oral solubility and bioavailability in blood plasma. Novel strategies involving CPT pharmacological and low doses combined with nanoparticles have indicated potent anticancer activity in vitro and in vivo. This systematic review aims to provide a comprehensive and critical evaluation of the anticancer ability of nano-CPT in various cancers as a novel and more efficient natural compound for drug development. Studies were identified through systematic searches of PubMed, Scopus, and ScienceDirect. Eligibility checks were performed based on predefined selection criteria. Eighty-two papers were included in this systematic review. There was strong evidence for the association between antitumor activity and CPT treatment. Furthermore, studies indicated that CPT nano-formulations have higher antitumor activity in comparison to free CPT, which results in enhanced efficacy for cancer treatment. The results of our study indicate that CPT nano-formulations are a potent candidate for cancer treatment and may provide further support for the clinical application of natural antitumor agents with passive targeting of tumors in the future.

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Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: An intelligent tumor-targeted delivery nanoplatform

Cited by 17 publications

References 43 publications

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Recent Advances in Improved Anticancer Efficacies of Camptothecin Nano-Formulations: A Systematic Review

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