Peptide-mediated cationic micelles drug-delivery system applied on a VEGFR3-overexpressed tumor.

Copolymers as a kind of drug delivery carrier always lack targeting efficiency. So a peptide conjugated to a drug delivery system has attracted much attention for tumor-targeted nanomedicine. Thus, we here report a conjugation compound consisting of a copolymer (PEG-b-PLL) and a peptide (Cys-Ile-Gln-Pro-Phe-Tyr-Pro, CP7). For receptor-mediated endocytosis by this peptide, the CP7-PEG-b-PLL conjugation significantly enhanced the chemotherapeutic efficacy as a potent nanocarrier compared with free DOX. The CP7-PEG-b-PLL exhibited excellent pharmacokinetic behavior via a radioactive iodine-131 (I) tracing method. With this, the CP7-PEG-b-PLL/DOX system showed better tumor growth inhibition when studied on A549 cell lines and subcutaneous tumor models, but with less toxicity than free DOX. All these results suggest that the CP7-modified drug cationic micelles could represent a novel platform for successful drug delivery toward VEGFR3-overexpressed tumors.

[1]  Weng Lin Tang,et al.  Practical Asymmetric Synthesis of a Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Ubrogepant , 2017 .

[2]  L. Trnková,et al.  Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and Challenges. , 2017, Chemical reviews.

[3]  Jie Liu,et al.  Novel small peptides derived from VEGF125-136: potential drugs for radioactive diagnosis and therapy in A549 tumor-bearing nude mice , 2017, Scientific Reports.

[4]  T. Lu,et al.  De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation. , 2017, Molecular pharmaceutics.

[5]  J. Rainey,et al.  Pyrene-Apelin Conjugation Modulates Fluorophore- and Peptide-Micelle Interactions. , 2017, The journal of physical chemistry. B.

[6]  Lei Yu,et al.  iNGR-Modified Liposomes for Tumor Vascular Targeting and Tumor Tissue Penetrating Delivery in the Treatment of Glioblastoma. , 2017, Molecular pharmaceutics.

[7]  Fan Huang,et al.  Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy. , 2017, ACS applied materials & interfaces.

[8]  Liangzhu Feng,et al.  Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy. , 2017, ACS nano.

[9]  M. Xie,et al.  Mannose Receptor Mediates the Immune Response to Ganoderma atrum Polysaccharides in Macrophages. , 2017, Journal of agricultural and food chemistry.

[10]  Diwei Ho,et al.  Colloidal Polymeric Platform for Facile Click-Assisted Ligand Functionalization and Receptor Targeting , 2016, ACS omega.

[11]  Jian Zhang,et al.  An Integrative Folate-Based Metal Complex Nanotube as a Potent Antitumor Nanomedicine as Well as an Efficient Tumor-Targeted Drug Carrier. , 2016, Bioconjugate chemistry.

[12]  Xiangliang Yang,et al.  Self-Assembled PAEEP-PLLA Micelles with Varied Hydrophilic Block Lengths for Tumor Cell Targeting. , 2016, ACS applied materials & interfaces.

[13]  Emma Gordon,et al.  Mechanisms and regulation of endothelial VEGF receptor signalling , 2016, Nature Reviews Molecular Cell Biology.

[14]  K. Ulbrich,et al.  Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies. , 2016, Chemical reviews.

[15]  A. Indra,et al.  A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[16]  R. Hargest,et al.  MTA1 Is Up-regulated in Colorectal Cancer and Is Inversely Correlated with Lymphatic Metastasis. , 2015, Cancer genomics & proteomics.

[17]  Johnson V. John,et al.  Poly(PEGA)-b-poly(L-lysine)-b-poly(L-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride. , 2015, ACS applied materials & interfaces.

[18]  Wim E Hennink,et al.  Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Π-Π Stacking Stabilized Polymeric Micelles. , 2015, ACS nano.

[19]  Jianhua Zhang,et al.  Amphiphilic polyelectrolyte/prodrug nanoparticles constructed by synergetic electrostatic and hydrophobic interactions with cooperative pH-sensitivity for controlled doxorubicin delivery. , 2015, ACS applied materials & interfaces.

[20]  Lin Yu,et al.  Thermogelling polymer-platinum(IV) conjugates for long-term delivery of cisplatin. , 2015, Biomacromolecules.

[21]  R. Shukla,et al.  Peptides Used in the Delivery of Small Noncoding RNA , 2014, Molecular pharmaceutics.

[22]  Guojun Liu,et al.  Triblock Terpolymers Bearing a Redox-Cleavable Junction and a Photo-Cross-Linkable Block , 2014 .

[23]  Anjie Dong,et al.  Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor. , 2014, Biomacromolecules.

[24]  Fabian Kiessling,et al.  Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines. , 2014, Nano letters.

[25]  A. Kishimura,et al.  Multicompartment micelles with adjustable poly(ethylene glycol) shell for efficient in vivo photodynamic therapy. , 2014, ACS nano.

[26]  D. Tien,et al.  Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model. , 2013, Bioorganic & medicinal chemistry letters.

[27]  S. Hahner,et al.  [(3)H]metyrapol and 4-[(131)i]iodometomidate label overlapping, but not identical, binding sites on rat adrenal membranes. , 2013, Molecular pharmaceutics.

[28]  P. Pandolfi,et al.  Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. , 2012, Cancer discovery.

[29]  Yifan Ma,et al.  Self-assembled cationic micelles based on PEG-PLL-PLLeu hybrid polypeptides as highly effective gene vectors. , 2012, Biomacromolecules.

[30]  T. Cheng,et al.  Analytical measurement of PEGylated molecules. , 2012, Bioconjugate chemistry.

[31]  O. Melnyk,et al.  Synthesis of thiazolidine thioester peptides and acceleration of native chemical ligation. , 2011, Organic letters.

[32]  Xian‐Zheng Zhang,et al.  Core-shell nanosized assemblies mediated by the alpha-beta cyclodextrin dimer with a tumor-triggered targeting property. , 2010, ACS nano.

[33]  F. Caruso,et al.  Biodegradable click capsules with engineered drug-loaded multilayers. , 2010, ACS nano.

[34]  S. Fukushima,et al.  Cyclic RGD Peptide-Conjugated Polyplex Micelles as a Targetable Gene Delivery System Directed to Cells Possessing αvβ3 and αvβ5 Integrins , 2007 .